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Tag: Microbiome

  • Mycobiome Communities 101: Their Effect on Health & Disease

    Mycobiome Communities 101: Their Effect on Health & Disease

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    Our results show that both beneficial (e.g. Faecalibacterium, Lactobacillus, Prevotella) as well as pathogenic (e.g. Serratia, Ruminococcus) microorganisms were detected in fecal samples of healthy subjects. Similarly, the fungal profile has both beneficial (e.g. Galactomyces, Pichia) and pathogenic (e.g. Candida albicans) microorganisms.  

    Figure 3 shows that even though subjects included in the study were healthy, their microbiome clustered together into three different groups (Groups 1, 2, and 3). Each group share a similar microbiome profile: Individuals in Group 1 shared a healthy microbiome profile, while those in Group 2 had elevated levels of harmful bacteria (Proteobacteria2). Finally, Group 3 individuals have elevated levels of Firmicutes (associated with obesity3). 

    Analysis of fungal profile of different groups showed that Ascomycota was the major fungal phyla, representing approximately 95% abundance in all groups. But what about the mycobiome component of these microbiome groups? In our analysis, not surprisingly, Candida species were the key players. The presence of Candida did not appear to be associated more strongly with any of the three groups—some of the microbiomes in each of the groups had high levels of Candida, and some did not.

    It is important to remember that Candida are normal inhabitants of the human gut—many people have Candida albicans, C. glabrata, and sometimes C. tropicalis and C. parapsilosis, and these people can be perfectly healthy. However, when Candida was present and elevated (as often happens after a course of antibiotics, or with immune system problems or gut permeability issues), the subjects tended to have an overgrowth of this fungus.

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    Mahmoud Ghannoum, Ph.D.

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  • New Method Uses Engineered Bacteria and AI to Sense and Record Environmental Signals

    New Method Uses Engineered Bacteria and AI to Sense and Record Environmental Signals

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    Newswise — New York, NY—May 9, 2023—Researchers in Biomedical Engineering Professor Tal Danino’s lab were brainstorming several years ago about how they could engineer and apply naturally pattern-forming bacteria. There are many bacteria species, such as Proteus mirabilis (P. mirabilis), that self-organize into defined patterns on solid surfaces that are visible to the naked eye. These bacteria can sense several stimuli in nature and respond to these cues by “swarming”—a highly coordinated and rapid movement of bacteria powered by their flagella, a long, tail-like structure that causes a whip-like motion to help propel them. 

    For inspiration, Danino’s team at Columbia Engineering, which has a good deal of experience using synthetic biology methods to manipulate bacteria, discussed where else they might find similar patterns in nature and what their functions might be. They noted how tree rings record tree age and climate history, and that sparked their idea of applying P. mirabilis rings as a recording system. They had also been interested in applying AI to characterize the distinct features of bacterial colony patterns, an approach that they realized could then be used to decode an engineered pattern. 

    “This seemed to us to be an untapped opportunity to create a natural recording system for specific cues,” said Danino, a member of Columbia’s Data Science Institute (DSI).

    In a new study, published May 4 in Nature Chemical Biology, the researchers worked with P. mirabilis, commonly found in the soil and water and occasionally the human gut, known for its bullseye-appearing colony patterns. When the bacteria are grown on a Petri dish of a solid growth media, they alternate between phases of bacterial growth, which make visible dense circles, and bacterial movement, called “swarming” movement, which expands the colony outwards.  

    The team engineered the bacteria by adding what synthetic biologists call “genetic circuits”—systems of genetic parts, logically compiled to make the bacteria behave in a desired way. The engineered bacteria sensed the presence of the researchers’ chosen input—ranging from temperature to sugar molecules to heavy metals such as mercury and copper—and responded by changing their swarming ability, which visibly changed the output pattern.  

    Working with Andrew Laine, Percy K. and Vida L. W. Hudson Professor of Biomedical Engineering and a DSI member  and Jia Guo, assistant professor of neurobiology (in psychiatry) at the Columbia University Irving Medical Center the researchers then applied deep learning–a state-of-the-art AI technique–to decode the environment from the pattern, in the same way scientists look at the rings in a tree trunk to understand the history of its environment. They used models that can classify patterns holistically to predict, for example, sugar concentration in a sample, and models that can delineate or “segment” edges within a pattern to predict, for example, the number of times the temperature changed while the colony grew. 

    An advantage of working with P. mirabilis is that, compared to many of the typical engineered bacterial patterns, the native P. mirabilis pattern is visible to the naked eye without costly visualization technology and forms on a durable, easy-to-work-with solid agar medium. These properties increase the potential to apply the system as a sensor readout in a variety of settings. Using deep learning to interpret the patterns can enable researchers to extract information about input molecule concentrations from even complex patterns. 

    “Our goal is to develop this system as a low-cost detection and recording system for conditions such as pollutants and toxic compounds in the environment ,” said Anjali Doshi, the study’s lead author and a recent PhD graduate from Danino’s lab. “To our knowledge, this work is the first study where a naturally pattern-forming bacterial species has been engineered by synthetic biologists to modify its native swarming ability and function as a sensor.”

    Such work can help researchers better understand how the native patterns form, and beyond that, can contribute to other areas of biotechnology beyond the area of sensors. Being able to control bacteria as a group rather than as individuals, and control their movement and organization in a colony, could help researchers build living materials at larger scales, and help with the Danino lab’s parallel goal of engineering bacteria to be living “smart” therapeutics, by enabling better control of bacterial behaviors in the body. 

    This work is a new approach for building macroscale bacterial recorders, expanding the framework for engineering emergent microbial behaviors. The team next plans to build on their system by engineering the bacteria to detect a wider range of pollutants and toxins and moving the system to safe “probiotic” bacteria. Ultimately, they aim to develop a device to apply the recording system outside of the lab.

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    About the Study

    Journal: Nature Chemical Biology

    The study is titled “Engineered bacterial swarm patterns as spatial records of environmental inputs.”

    Authors are: Anjali Doshi 1 , Marian Shaw 1 , Ruxandra Tonea1 , Soonhee Moon1 , Rosalía Minyety1 , Anish Doshi2 , Andrew Laine1 , Jia Guo3,4 & Tal Danino 1,5,61 Department of Biomedical Engineering, Columbia University2 Department of Electrical Engineering and Computer Sciences, University of California, Berkeley3 Department of Psychiatry, Columbia University4 Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University5 Herbert Irving Comprehensive Cancer Center, Columbia University6 Data Science Institute, Columbia University

    This work was supported by an NSF CAREER Award (1847356 to T.D.), Blavatnik Fund for Innovations in Health (T.D.), and NSF Graduate Research Fellowship (A.D., Fellow ID 2018264757).

    A.D., M.S., J.G., A.L. and T.D. are named as inventors on a provisional patent application that has been filed by Columbia University with the US Patent and Trademark Office related to all aspects of this work. The remaining authors declare no competing interests. 

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    LINKS:

    Paper: https://www.nature.com/articles/s41589-023-01325-2
    DOI:  10.1038/s41589-023-01325-2

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    Columbia University School of Engineering and Applied Science

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  • First microbiome-targeting drug using CRISPR created by scientists

    First microbiome-targeting drug using CRISPR created by scientists

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    Newswise — Many people have experienced infections from E. coli, which are primarily seen as inconvenient and unpleasant. For some patients, like those with blood cancer, however, there is a risk that the bacteria will travel into the bloodstream. In those cases, an E. coli infection is too often fatal. The mortality rate is 15-20%.

    The predominant cure for such infections is the use of antibiotics that have detrimental effects on the patient’s microbiome, which play a key part in our physical and emotional well-being, and other side effects. Furthermore, growing problems with antibiotic resistance render such treatments less effective in treating infections.

    An international team of scientists has now engineered the first published CRISPR-based candidate (see fact box) for a drug that targets E. coli directly and leaves the microbiome intact. A new paper in Nature Biotechnology titled ‘Engineered phage with antibacterial CRISPR–Cas selectively reduce E. coli burden in mice’ describes the development of the drug candidate to a stage where it is ready for tests on humans.

    Through extensive use of synthetic biology, the team designed four bacterial viruses that use CRISPR technology to kill the unwanted bacteria precisely.

    “We believe that a narrow spectrum drug with these properties could be very useful to cancer patients, among others, who often get serious infections that are difficult to treat with current antibiotics,” says Morten Otto Alexander Sommer, a professor at DTU Biosustain, Co-founder of SNIPR Biome, and lead author of the paper.

    The work was carried out in collaboration with JAFRAL (Slovenia), JMI Laboratories (US), and Division of Infectuous Diseases at Weill Cornell Medicine (US).

    Engineering phages to target E. coli

    The team, primarily based at SNIPR Biome, screened a library of 162 naturally occurring phages (viruses that kill specific bacteria; see fact box). They found that eight of these phages showed promise in targeting E. coli. They then engineered the phages through gene editing to improve their ability to target E. coli.

    A cocktail of four of these phages, which they named SNIPR001, very effectively targeted bacteria in biofilms and reduced the number of E. coli in a manner that surpassed that of  naturally occurring phages. Further, they showed that the cocktail of phages was tolerated well in the gut of mice and mini pigs while reducing the emergence of E. coli. SNIPR001 is now in clinical development and has been granted a Fast-Track designation (expedited review) by the US Food and Drug Administration.

    FACT BOX: An overview of the SNIPR001 creation process:

    1. Naturally occurring phages are screened against a panel of E. coli strains.
    2. Phages with broad activity against E. coli are tail fibre engineered and/or armed with CRISPR–Cas systems containing sequences specific to E. coli, creating CAPs (Cas-armed phages).
    3. These CAPs are tested for host range, in vivo efficacy, and CMC specifications.

    SNIPR001 comprises four complementary CAPs and is a new precision antibiotic that selectively targets E.coli to prevent bacteremia in haematological cancer patients at risk of neutropenia (low levels of white blood cells).

    Blood cancer patients are first in line

    The reason this new development is exciting for blood cancer patients has to do with side effects stemming from their chemotherapy treatment. It causes the patient’s bone marrow to produce fewer blood cells and inflammation of the intestines. The latter increases the intestines’ permeability allowing bacteria from the gut to travel into the bloodstream. This combination of side effects leaves the patient vulnerable to infections from bacteria like E. coli. In such cases, the

    Today, patients at risk (i.e., with low levels of white blood cells) receive antibiotic treatments ahead of their chemotherapy, but in some cases, E. coli shows very high resistance to commonly used antibiotics. Also, the antibiotics themselves have several side effects that in some cases reduce the effect of the cancer treatments.

    “We need a wider variety of options available to treat these patients, preferably ones where we can specifically target the bacteria responsible to avoid side effects and that do not add to the problem of antibiotic resistance,” says Morten Otto Alexander Sommer.

    In recent years, researchers have been looking back towards using phages to treat infections because of the increase in antibiotic resistance. Before antibiotics were broadly available, phages were widely used and studied in countries that were then part of the Soviet Union. Still, there are few clinical trials, and the results haven’t been convincing, according to the paper.

    “Through emerging technologies like CRISPR, the use of phages in treating infections has become a viable pathway. As our results show, there is potential for enhancing naturally occurring phages through genetic engineering. It is my hope that this approach may also serve as a blueprint for new antimicrobials targeting resistant pathogens,” says Morten Otto Alexander Sommer.

    FACT BOX: CRISPR, phages, and phage therapy

    CRISPR technology is a way for scientists to edit DNA sequences in cells. It’s based on a defence mechanism bacteria naturally use to protect themselves. CRISPR technology uses a molecule called Cas9, which works like a pair of scissors to cut DNA at a specific spot.

    After the cut, the DNA can be fixed, or a new piece can be added. Scientists can use this tool to create genetically modified organisms, find new ways to treat genetic diseases, and learn more about how genes work.

    Phages are tiny viruses that can kill specific bacteria. They’re everywhere on Earth and help regulate bacterial populations and nutrient cycling. They infect and kill bacteria, and when the bacteria die, they release nutrients into the environment.

    Scientists use phages to treat bacterial infections, which is called phage therapy. They identify and isolate phages that can kill a specific bacterial strain and use them to fight infections caused by that strain.

    Phage therapy has some advantages to antibiotics, like targeting specific bacteria without side effects and potentially reducing antibiotic resistance.

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    Technical University of Denmark (DTU)

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  • Gut germs use strong substances to avoid antibiotics.

    Gut germs use strong substances to avoid antibiotics.

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    Newswise — The discovery shows why it can be so difficult to tackle drug-resistant bacteria, but does provide a possible avenue for tackling the problem. The super-polymer structures the bacteria use to transfer genes could also be exploited for precise drug delivery in future medicine.

    Gut bacteria form extracellular appendages called F-pili to connect to each other and transfer packets of DNA, called genes, that allow them to resist antibiotics. It was thought that the harsh conditions inside human and animal guts, including turbulence, heat, and acids, would break the F-pili, making transfer more difficult.

    However, new research by a team led by Imperial College London researchers has shown that the F-pili are actually stronger in these conditions, helping the bacteria transfer resistance genes more efficiently, and to clump into ‘biofilms’ – protective bacterial consortia – that help them fend off antibiotics.

    The results are published in Nature Communications.

    First author Jonasz Patkowski, from the Department of Life Sciences at Imperial, said: “The death toll from antimicrobial resistance is expected to match cancer by 2050, meaning we urgently need new strategies to combat this trend. Much of the spread of resistance is driven by bacteria swapping genes, so detailed understanding of this process could lead to new ways to interrupt it.”

    Not so fragile

    Different classes of bacteria use different types of pili to transfer genes in a process called conjugation. A classic experiment seemed to show that this process was fragile and could be interrupted by agitation, but this left a mystery: why do so many bacteria living in harsh conditions like guts use these systems if they are so fragile?

    The team therefore set out to test this assumption. By shaking E. coli bacteria while they used F-pili during conjugation, they discovered that agitation actually increased the efficiency of gene transfer between bacteria. They also observed that after transferring genes, the conjugated bacteria in shaken conditions clumped together more easily to form biofilms, which protect inner bacteria from the surrounding antibiotic molecules.

    To determine how the F-pili are able to do this, the team subjected them to a strength test by mounting a bacterium on a stage, connecting a glass bead using ‘molecular tweezers’ to the end of one of its F-pili, and pulling. The F-pili proved highly elastic, with spring-like properties that prevented them from breaking.

    They also tested the F-pili’s ability to withstand other common gut conditions, subjecting them to sodium hydroxide, urea, and excessively high temperatures of 100°C – all of which the F-pili survived.

    Molecular properties

    The team then went a step further, looking at the F-pili on a molecular level to see what gives them these incredible properties. They are primarily made up of F-pilin ‘subunits’ with interlinked phospholipid molecules.

    By modelling the F-pili without the phospholipids, the team showed how important these molecules are for the structure’s springiness and elastic strength. Repeating the pulling experiment revealed that the subunits quickly disassemble without the phospholipids supporting them, proving their novel role as a ‘molecular glue’ in long biopolymers.

    Lead researcher Dr Tiago Costa, from the Department of Life Sciences at Imperial, said: “Making F-pili is very costly to the bacteria in terms of resources and energy, so it’s no surprise they are worth the effort. We have shown how F-pili accelerate the spread of antibiotic resistance and biofilm formation in turbulent environments, but the challenge now is to find ways to combat this very efficient process.”

    While it would be advantageous to break F-pili in pathogenic bacteria, their properties could be helpful if we can engineer them for use in, for example, drug delivery. Patkowski explained: “It’s hard to find a tubular appendage with such strong properties. Bacteria use it to transfer genes, but if we could mimic these properties, we could use similar structures to precisely deliver drugs where they are needed in the body.”

    https://www.imperial.ac.uk/news/244513/gut-bacteria-superpolymers-dodge-antibiotics/

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    Imperial College London

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  • An Expert Explains Why The Microbiome Is The Key To Healthy Skin

    An Expert Explains Why The Microbiome Is The Key To Healthy Skin

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    In expanding the understanding of this invisible, microbial ecosystem–we better understand ourselves. In the episode, we get into more of the details of how this research is done, what the microbiome could have looked like, and ultimately, what it means for modern-day folks. 

    But as a sneak peek, let’s talk about the curious case of essential amino acids and essential fatty acids. “There are what we call essential amino acids and essential fatty acids. What this means is that we need them, but we don’t make them ourselves,” he tells me. 

    The essential fatty acids omega-6 and omega-31 are vital for skin barrier function and overall health. Without them, we may experience inflammation, transepidermal water loss, and all the skin concerns that come with those—sensitivities, fine lines, dullness, discoloration, and redness. 

    “And that was always very puzzling for researchers: Like, if they’re so badly needed, why aren’t we making them?,” he explains. “And the reason was we never had to. We emerged into a world where microbes made those for us. So our bodies never had to have those metabolic pathways.”

    Essentially many of the nutrients we prioritize in skin care, are the very things that the microbiome used to create for us. (Sometimes we call these postbiotics, or the byproducts of the living organisms on the skin.) We’re coming closer to understanding how we can best care for this microbial world, and replicate what has been lost, but we are by no means even close to done.

    “This microbial world is the connective tissue for us biologically,” he says. “And we need to rebuild our relationship with it.” 

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    Alexandra Engler

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  • Fred Hutch at AACR: New targets for cancer therapies, experts available in diversity and cancer screening tests — and Fred Hutch’s Philip Greenberg becomes AACR president

    Fred Hutch at AACR: New targets for cancer therapies, experts available in diversity and cancer screening tests — and Fred Hutch’s Philip Greenberg becomes AACR president

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    Newswise — SEATTLE — April 6, 2023 — Experts from Fred Hutchinson Cancer Center will present their latest findings on targets in RIT1-driven cancers, ROR1 CAR T-cell immunotherapy, interplay of the microbiome and genetics in colorectal cancer and more at the annual meeting of the American Association for Cancer Research, to be held April 14-19 in Orlando, Florida. 

    Other meeting highlights include:

    Philip Greenberg, M.D. of Fred Hutch will become AACR president.

    Public health researcher and biostatistician Ruth Etizioni, Ph.D. will discuss new and emerging tests for early detection of cancer.

    Christopher Li, M.D., MPH, a national leader in diversity, equity and inclusion efforts at cancer centers, will best practices and strategies to enhance diversity. 

    Below are highlights of work to be presented, and you can follow Fred Hutch’s AACR updates on Twitter #AACR23.

    For media requests during AACR, please contact . 

    AACR news

    Meet and Greet: Meet the editors-in-chief of Cancer Immunology Research Monday, April 17, 2023, 9:30-10:30 a.m. 

    Meeting: Meet the 2023-2024 AACR President, Philip Greenberg Tuesday, April 18, 2023, 1:30-2:30 p.m.

    Fred Hutch’s Philip Greenberg, M.D., one of two editors-in-chief of AACR’s Cancer Immunology Research, will participate in an April 17 discussion of the scope and types of research manuscripts they’re looking to publish. Greenberg, currently president-elect of AACR, will become AACR president during the meeting and be at the April 18 “Meet the 2023-2024 AACR President” session. He leads the Program in Immunology at Fred Hutch and holds the Rona Jaffe Foundation Endowed Chair.  

    Early detection and screening

    Educational session: How can we realize the promise of novel technologies for early cancer detection? Presentation: Developing realistic expectations for new cancer screening tests Friday, April 14, 2023, 3:01-3:21 p.m. Presenter: Ruth Etzioni, Ph.D.

    Public health researcher and biostatistician Ruth Etzioni, Ph.D. will join an educational session to talk about novel cancer screening tests based on liquid biopsies, with a particular focus on multi-cancer early detection testing. She said that while there are some studies that show how well the tests detect different cancers, the extent to which this will translate into lives saved is still unclear. Etzioni, who holds the Rosalie and Harold Rea Brown Endowed Chair at Fred Hutch and received a $7.4 million National Cancer Institute grant to study cancer diagnostics, will discuss the process by which population screening leads to reduction in cancer deaths, why some past cancer screening trials have led to disappointing results and what needs to be done now to generate convincing evidence that population screening using the new tests will reduce cancer deaths. 

    Precision oncology

    Educational session: Tumor heterogeneity: Rapid autopsy to longitudinal biopsies Presentation: Intra and inter-tumor heterogeneity across cancer metastases: A reality check for targeted therapeutics and the utility of non-invasive biomarkers Saturday, April 15, 2023, 3:16-3:33 p.m. Presenter: Peter Nelson, M.D.

    In a session on the use of rapid autopsies to understand cancer metastasis, Peter Nelson, M.D. will discuss the impact of tumor heterogeneity on treatment resistance. Nelson, who is a prostate cancer expert and is the vice president of Precision Oncology at Fred Hutch, will also explain how studies of metastatic tumors improve our understanding of molecular imaging such as PET scans as well as minimally-invasive diagnostic methods including circulating tumor DNA. Nelson directs the Stuart and Molly Sloan Precision Oncology Institute at Fred Hutch and holds an endowed chair with the same name.  

    Session: Small cell lung cancer: Moving biology to the clinic Presentation: Measuring and modulating SCLC transcriptional heterogeneity from murine models to clinical trials Monday, April 17, 2023, 1:00-1:20 p.m. Presenter: Joseph Hiatt, M.D., Ph.D. (On Twitter and LinkedIn)

    Physician-scientist Joseph Hiatt, M.D., Ph.D. will give an update on Fred Hutch preclinical research that has identified a molecular pathway that could make more cases of small cell lung cancer responsive to checkpoint inhibition. The approach is now being studied in a clinical trial. Hiatt, who is a research fellow in the MacPherson lab at Fred Hutch, will also present a new liquid biopsy method to predict subtypes of small cell lung cancer using cell-free DNA. This could be used to link patients’ subtypes to their treatment outcomes to help personalize clinical trial enrollment. The work is part of the Fred Hutch Lung Specialized Project of Research Excellence (SPORE), a five-year $13 million grant from the National Cancer Institute to expedite lung cancer research from the lab to the clinic. 

    Session: Ras-related signaling Poster: Protein-level regulation of wild-type and mutant RIT1 by the deubiquitinase USP9X Monday, April 17, 2023, 1:30-5 p.m. Presenter: Amanda Riley (On LinkedIn)

    Mutations in the gene RIT1 account for about 13,500 cases of non-small cell lung cancer diagnoses each year, with limited treatment options. Graduate student Amanda Riley, working in the Fred Hutch lab of Alice Berger, Ph.D., will give an update on their work to find targeted therapies for RIT1-driven cancers. They’ve identified a regulator of RIT1, a protein called USP9X. Using mouse models and existing inhibitors of USP9X, the researchers are evaluating this potential drug target. The project is part of Berger’s 7-year NIH MERIT award to pursue targeted therapies for mutations in lung cancer. Berger holds the Innovators Network Endowed Chair at Fred Hutch, follow her on Twitter. 

    Cancer biology

    Major symposium: Targeting RNA splicing in cancer and the immune system Presentation: From splicing to polyadenylation in tumor immunity Sunday, April 16, 2023, 1:55-2:15 p.m. Presenter: Robert Bradley, Ph.D. (On Twitter)

    Computational biologist and biophysicist Robert Bradley, Ph.D. will present new work on a biological process that’s growing in attention for its role in controlling cancer growth. Alternative polyadenylation is part of making mRNA and it’s disrupted in many cancers, though it’s not clear how the dysregulation contributes to tumors. Bradley, who holds the McIlwain Family Endowed Chair in Data Science at Fred Hutch, will discuss a CRISPR-Cas9-based screen to test the functional importance of alternative polyadenylation to tumor growth. 

    Cellular immunotherapy

    Minisymposium: Genetically engineered anticancer T cells Presentation: NKTR-255, a polymer-conjugated IL-15, dramatically improves ROR1 CAR-T cell persistence and anti-tumor efficacy in an autochthonous model of ROR1+ lung cancer Sunday, April 16, 2023, 4:10-4:25 p.m. Presenter: Sam Nutt

    Using a mouse model of lung cancer that closely resembles human disease, graduate student Sam Nutt in the Fred Hutch lab of Shivani Srivastava, Ph.D. (on Twitter) will present a study on whether NKTR-255, a drug that stimulates the immune system to fight cancer, can improve the anticancer effects of chimeric antigen receptor (CAR) T cells. The Fred Hutch team is using a CAR-T cell targeting the tumor antigen ROR1, which is a marker on many breast and lung cancer patients. Their findings suggest that NKTR-255 treatment improves the persistence and function of ROR1 CAR T cells, and that these two therapies work together to boost immune function in the tumor microenvironment, resulting in significantly improved tumor control. The team is continuing to evaluate the combined approach for treatment of solid tumors. Read more about the lab’s work to develop cellular therapies for solid tumors.

    Colorectal cancer risk and prevention

    Session: Biological and behavioral factors in cancer surveillance, prevention and survivorship Poster: Evaluation of intra-tumoral pks+ E. coli, enterotoxigenic B. fragilis and Fusobacterium nucleatum and in early onset disease, in colorectal cancer cases Monday, April 17, 2023, 1:30-5:00 p.m. Presenter: Meredith Hullar, Ph.D. 

    Meredith Hullar, Ph.D., a principal staff scientist at Fred Hutch, studies the gut microbiome and its interplay with diet and cancer risk. She will present a new study that revealed different patterns of microbes in colorectal cancer tumors that are present in patients with early onset colorectal cancer, which has increased in incidence in people who are 50 years old and younger. Since some microbes can help tumors grow, understanding the microbiome may help predict which colorectal cancer patients will have increased odds of lower survival and may support targeted intervention strategies to improve survivorship. Learn more about her work in a Fred Hutch news story.

    Session: Aging, immune factors and metabolomics Poster: Association between HLA-KIR allele interaction combinations and density of T-cell subsets in colorectal cancer Monday, April 17, 2023, 1:30-5:00 p.m. Presenter: Claire E. Thomas, Ph.D., MPH (On Twitter)

    Session: Diet, alcohol, tobacco use, and other lifestyle factors Poster: Lifestyle and environmental factors in relation to colorectal cancer risk and survival by colibactin tumor mutational signature status Wednesday, April 19, 2023, 9:00 a.m.-12:30 p.m. Presenter: Claire E. Thomas, Ph.D., MPH (On Twitter)

    Claire E. Thomas, Ph.D., MPH, a post-doctoral researcher at Fred Hutch, will present two posters looking at genetic and molecular risks underlying colorectal cancer. In the first poster, she examines whether immune function gene combinations are related to T-cell density within colorectal cancer tumors. The findings could help determine how an individual’s genetic background is related to T-cells and immune response to fight cancer. 

    In a second poster, Thomas will present a study examining whether lifestyle and environmental factors are differentially associated with colorectal cancer risk and survival for cases with and without the mutational signature SBS88. SBS88 is present in some colorectal cancer tumors and is related to production of the genotoxin colbactin from exposure to some strains of Escherichia coli. The findings show that among cases with the SBS88 signature, higher BMI category was associated with worse colorectal cancer outcomes. 

    Thomas works with Fred Hutch’s Ulrike Peters, Ph.D., MPH, who is a molecular and genetic epidemiologist and holds the Fred Hutch 40th Anniversary Endowed Chair, and with Amanda Phipps, Ph.D., MPH, an epidemiologist. The research team aims to understand underlying genetic risks in cancer and how to intervene. A recent Nature Genetics study from the Peters team identified 100 new genetic risk variants in colorectal cancer.

    Diversity, equity and inclusion

    Meet-the-expert session: Plan to enhance diversity: Opportunities, challenges, best practices and innovative strategies to advance a culture of inclusive excellence at cancer centers Tuesday, April 18, 2023, 7:00-7:45 a.m. Presenter: Christopher Li, M.D., Ph.D. (On LinkedIn)

    Christopher Li, M.D., Ph.D., vice president of Faculty Affairs and Diversity at Fred Hutch, is a nationally recognized leader in efforts to ensure that cancer research benefits all people. At AACR, he will insights from his efforts to help build and maintain a diverse, equitable and inclusive workforce at Fred Hutch and to collaborate with leaders at other cancer centers. Li, who holds the Helen G. Edson Endowed Chair for Breast Cancer Research, is also an epidemiologist who studies breast cancer risk factors, breast cancer recurrence and cancer health disparities.

    Clinical trials

    Major symposium: Sex hormones and cancer Presentation: Sex differences in severe adverse events in patients receiving immunotherapy, targeted therapy, or chemotherapy in Cancer clinical trials: An evidentiary perspective Tuesday, April 18, 2023, 1:25-1:45 p.m. Presenter: Joseph Unger, Ph.D. (On Twitter)

    Biostatistician and health services researcher Joseph Unger, Ph.D. will insights based on findings he published in Journal of Clinical Oncology in how women experience greater adverse effects from cancer treatment, whether it’s chemotherapy, targeted therapy or immunotherapy. The data came from more than 23,000 people participating in 202 clinical trials as part of the SWOG Cancer Research Network, which described the study in a blog post. Unger uses big data to understand treatment outcomes and disparities in cancer, with the aim of revealing problems in cancer care that then allow for ways to predict and prevent the issues before they impede patients.  

    Late-breaking poster session: Clinical research 3 Poster: Biomarker analysis from AMPECT correlating response to nab-sirolimus with TSC1 and TSC2 inactivating alterations Wednesday, April 19, 9 a.m.-12:30 p.m. Presenter: Lee Cranmer, M.D., Ph.D.

    Lee Cranmer, M.D., Ph.D. leads the Bob and Eileen Gilman Family Sarcoma Research Program at Fred Hutch. A recent Fred Hutch news story featured a patient Cranmer treated for a type of cartilage cancer, called chondrosarcoma.

    Note: Fred Hutch and its scientists who contributed to these discoveries may stand to benefit from their commercialization. See links above to AACR abstracts for more details on individual researchers’ disclosures.

    The clinical trials referenced above involve investigational products and/or therapies that have not been approved for commercial marketing by the U.S. Food and Drug Administration or any other regulatory authority. Results may vary, and encouraging results from early-stage clinical trials may not be supported in later-stage clinical trials. No conclusions should be drawn from the information in this report about the safety, efficacy or likelihood of regulatory approval of these investigational products and/or therapies.

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    Fred Hutchinson Cancer Center unites individualized care and advanced research to provide the latest cancer treatment options and accelerate discoveries that prevent, treat and cure cancer and infectious diseases worldwide.

    Based in Seattle, Fred Hutch is an independent, nonprofit organization and the only National Cancer Institute-designated cancer center in Washington. We have earned a global reputation for our track record of discoveries in cancer, infectious disease and basic research, including important advances in bone marrow transplantation, immunotherapy, HIV/AIDS prevention, and COVID-19 vaccines. Fred Hutch operates eight clinical care sites that provide medical oncology, infusion, radiation, proton therapy and related services and has network affiliations with hospitals in four states. Fred Hutch also serves as UW Medicine’s cancer program.

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    Fred Hutchinson Cancer Center

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  • A healthy microbiome may prevent deadly infections in critically ill people

    A healthy microbiome may prevent deadly infections in critically ill people

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    Newswise — Twenty to 50 per cent of all critically ill patients contract potentially deadly infections during their stay in the intensive care unit or in hospital after being in the ICU – markedly increasing the risk of death.

    “Despite the use of antibiotics, hospital-acquired infections are a major clinical problem that persists to be a huge issue for which we don’t have good solutions,” says Dr. Braedon McDonald, MD, PhD, an intensive care physician at the Foothills Medical Centre (FMC) and assistant professor at the Cumming School of Medicine (CSM). “We tackled this issue from a different angle. We looked at the body’s natural defense to infection to better understand why some people are more susceptible to these deadly infections.”

    The study involved 51 patients newly admitted to the intensive care unit (ICU) at FMC. Patients were studied over the first week of acute critical illness. The research showed that the gut microbiota and systemic immunity work together as a dynamic “metasystem,” in which problems with gut microbes and immune system dysfunction are associated with significantly increased rates of hospital-acquired infections.

    “The signal that we’ve seen in our research is that a family of bacteria, that naturally live in the gut, seems to be important for directing the immune system,” says Jared Schlechte, PhD candidate in McDonald’s lab and first author of the study. “However, during critical illness the microbiome becomes injured allowing these bacteria to start taking over.”

    The study published in Nature Medicine found that patients who experienced an abnormal increase in the growth of this common bacteria, called a bloom, were at the highest risk of severe infections.

    “This information is important because it gives us a whole new avenue to start thinking about not just ways to treat infections, but a potential treatment to prevent them,” says McDonald. “The findings suggest that if we want to fight infection, we can’t just target these bad bacteria in isolation and the immune system in isolation. We really need to have a more holistic view of how things are functioning.” McDonald says the study’s findings

    As a next step, McDonald and the team plan to launch a randomized, controlled clinical trial – based on a precision medicine approach that borrows from probiotics therapy, and utilizes multiple different bacteria engineered to specifically target the bacteria identified in the study. People who agree to participate will be given engineered microbiomes.

    “What we’re trying to do is restore the normal mechanism that work when we’re healthy, and take advantage of that to help protect people from infections,” McDonald says.

    UCalgary faculty co-authors included Drs. Christopher Doig, MD, Kathy McCoy, PhD, and Mary Dunbar, MD. PhD candidate Amanda Zucoloto, along with research technician and laboratory manager Ian-Ling Yu, also co-authored the study. The study was supported by the Canadian Institutes of Health Research and the Alberta Health Services Critical Care Strategic Clinical Network. 

    Braedon McDonald is an assistant professor in the Department of Critical Care Medicine at the Cumming School of Medicine (CSM), an intensive care physician at the Foothills Medical Centre, and a member of the Snyder Institute for Chronic Diseases at CSM.

    The Snyder Institute for Chronic Diseases is a team of more than 480 clinician-scientists and basic scientists dedicated to uncovering new knowledge leading to disease prevention, tailored medical applications and ultimately cures for those with chronic and infectious disease. Visit snyder.ucalgary.ca and follow @SnyderInstitute to learn more.

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  • The heart benefits of walnuts likely come from the gut

    The heart benefits of walnuts likely come from the gut

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    Newswise — A new study examining the gene expression of gut microbes suggests that the heart-healthy benefits of walnuts may be linked to beneficial changes in the mix of microbes found in our gut. The findings could help identify other foods or supplements with similar nutritional benefits.

    Researchers led by Kristina S. Petersen from Texas Tech University in Lubbock found that introducing walnuts into a person’s diet may alter the gut’s mix of microbes — known as the microbiome — in a way that increases the body’s production of the amino acid L-homoarginine. Homoarginine deficiency has been linked to higher risk for cardiovascular disease.

    “Research has shown that walnuts may have heart-healthy benefits like lowering cholesterol levels and blood pressure,” said Mansi Chandra, an undergraduate researcher at Juniata College in Huntingdon, Pennsylvania. “This motivated us to look at how walnuts benefited the gut microbiome and whether those effects led to the potential beneficial effects. Our findings represent a new mechanism through which walnuts may lower cardiovascular disease risk.”

    Chandra will present the new findings at Discover BMB, the annual meeting of the American Society for Biochemistry and Molecular Biology, March 25–28 in Seattle.

    The researchers used an approach known as metatranscriptomics to study the gene expression of gut microbes. This recently developed technology can be used to quantify gene expression levels and monitor how these levels shift in response to various conditions such as dietary changes.

    “To our knowledge, this is the first study to use metatranscriptomics analysis for studying the impact of walnut consumption on the gut microbiota gene expression,” Chandra said. “These exploratory analyses contribute to our understanding of walnut-related modulation of gut microbiome, which could be very impactful in learning how gut health impacts our heart health in general.”

    The metatranscriptomics analysis used samples acquired from a previously performed controlled-feeding study in which 35 participants with high cardiovascular risk were put on a two-week standard Western diet and then randomly assigned to one of three study diets. The study participants followed each diet for six weeks with a break between each.

    The diets included one that incorporated whole walnuts, one that included the same amount of omega-3 fatty acid alpha-linolenic acid, or ALA, and polyunsaturated fatty acids as the walnut diet but without walnuts, and one that partially substituted another fatty acid known as oleic acid for the same amount of ALA found in walnuts but without consumption of any walnuts. The diets were designed to provide information about how walnuts affected cardiovascular health due to their bioactive compounds and ALA content and whether walnut ALA is the best substitute for dietary saturated fat compared to oleic acid.

    For the new work, researchers used metatranscriptomics to analyze gene expression and the bacteria in the gastrointestinal tract from fecal samples collected shortly before the participants finished the run-in diet and each of the three study diets.

    The analysis revealed higher levels of Gordonibacter bacteria in the gut of participants on the walnut diet. This bacterium converts the plant polyphenols ellagitannins and ellagic acid into metabolites that allow them to be absorbed by the body. Participants consuming the walnut diet also showed higher levels of expression for several genes that are involved in important metabolic and biosynthetic pathways, including ones that increase the body’s production of the amino acid L-homoarginine.

    Although more work is needed to confirm these observations, the research could eventually help inform dietary interventions based on walnuts. “Since a lot of people are allergic to nuts, these findings also suggest that other food supplements that boost the endogenous production of homoarginine may also be helpful,” Chandra said.

    Next, the researchers would like to apply metabolomic and proteomic analyses to identify the final products of the genes that showed higher levels of expression. This would allow them to better understand the biological mechanisms at work.

     

    Mansi Chandra will present this research during the Undergraduate Poster Competition from noon to 3:30 p.m. PDT on Saturday, March 25, and during the poster session from 4:30 to 6:30 p.m. PDT on Sunday, March 26, in Exhibit Hall 4AB of the Seattle Convention Center (Poster Board No. 25) (abstract). Contact the media team for more information or to obtain a free press pass to attend the meeting.

     

    Image available.

     

    This release may include updated data or information that differs from the abstract submitted to the Discover BMB meeting.

     

    Kristina S. Petersen was previously affiliated with Pennsylvania State University.

     

    This study was funded by the California Walnut Commission. The research was also supported by the Penn State Clinical and Translational Research Institute, Pennsylvania State University Clinical and Translational Science Award and NIH/National Center for Advancing Translational Sciences (Grant UL1TR000127).

     

    About the American Society for Biochemistry and Molecular Biology (ASBMB)

    The ASBMB is a nonprofit scientific and educational organization with more than 12,000 members worldwide. Founded in 1906 to advance the science of biochemistry and molecular biology, the society publishes three peer-reviewed journals, advocates for funding of basic research and education, supports science education at all levels, and promotes the diversity of individuals entering the scientific workforce. www.asbmb.org

    Find more news briefs and tipsheets at https://discoverbmb.asbmb.org/newsroom.

     

     

     

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  • Humans are leaving behind a ‘frozen signature’ of microbes on Mount Everest

    Humans are leaving behind a ‘frozen signature’ of microbes on Mount Everest

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    Newswise — Almost 5 miles above sea level in the Himalayan mountains, the rocky dip between Mount Everest and its sister peak, Lhotse, lies windswept, free of snow. It is here at the South Col where hundreds of adventurers pitch their final camp each year before attempting to scale the world’s tallest peak from the southeastern side.

    According to new University of Colorado Boulder-led research, they’re also leaving behind a frozen legacy of hardy microbes, which can withstand harsh conditions at high elevations and lie dormant in the soil for decades or even centuries.

    The research not only highlights an invisible impact of tourism on the world’s highest mountain, but could also lead to a better understanding of environmental limits to life on Earth, as well as where life may exist on other planets or cold moons. The findings were published last month in Arctic, Antarctic, and Alpine Research, a journal published on behalf of the Institute of Arctic and Alpine Research (INSTAAR) at CU Boulder.

    “There is a human signature frozen in the microbiome of Everest, even at that elevation,” said Steve Schmidt, senior author on the paper and professor of ecology and evolutionary biology.

    In decades past, scientists have been unable to conclusively identify human-associated microbes in samples collected above 26,000 feet. This study marks the first time that next-generation gene sequencing technology has been used to analyze soil from such a high elevation on Mount Everest, enabling researchers to gain new insight into almost everything and anything that’s in them.

    The researchers weren’t surprised to find microorganisms left by humans. Microbes are everywhere, even in the air, and can easily blow around and land some distance away from nearby camps or trails.

    “If somebody even blew their nose or coughed, that’s the kind of thing that might show up,” said Schmidt.

    What they were impressed by, however, was that certain microbes which have evolved to thrive in warm and wet environments like our noses and mouths were resilient enough to survive in a dormant state in such harsh conditions.

    Life in the cryosphere

    This team of CU Boulder researchers—including Schmidt, lead author Nicholas Dragone and Adam Solon, both graduate students in the Department of Ecology and Evolutionary Biology and the Cooperative Institute for Research in Environmental Science (CIRES)—study the cryobiosphere: Earth’s cold regions and the limits to life in them. They have sampled soils everywhere from Antarctica and the Andes to the Himalayas and the high Arctic. Usually, human-associated microbes don’t show up in these places to the extent they appeared in the recent Everest samples.

    Schmidt’s work over the years connected him with researchers who were headed to Everest’s South Col in May of 2019 to set up the planet’s highest weather station, established by the National Geographic and Rolex Perpetual Planet Everest Expedition.

    He asked his colleagues: Would you mind collecting some soil samples while you’re already there?

    So Baker Perry, co-author, professor of geography at Appalachian State University and a National Geographic Explorer, hiked as far away from the South Col camp as possible to scoop up some soil samples to send back to Schmidt.

    Extremes on Earth, and elsewhere

    Dragone and Solon then analyzed the soil in several labs at CU Boulder. Using next-generation gene sequencing technology and more traditional culturing techniques, they were able to identify the DNA of almost any living or dead microbes in the soils. They then carried out extensive bioinformatics analyses of the DNA sequences to determine the diversity of organisms, rather than their abundances.  

    Most of the microbial DNA sequences they found were similar to hardy, or “extremophilic” organisms previously detected in other high-elevation sites in the Andes and Antarctica. The most abundant organism they found using both old and new methods was a fungus in the genus Naganishia that can withstand extreme levels of cold and UV radiation.

    But they also found microbial DNA for some organisms heavily associated with humans, including Staphylococcus, one of the most common skin and nose bacteria, and Streptococcus, a dominant genus in the human mouth.

    At high elevation, microbes are often killed by ultraviolet light, cold temperatures and low water availability. Only the hardiest critters survive. Most—like the microbes carried up great heights by humans—go dormant or die, but there is a chance that organisms like Naganishia may grow briefly when water and the perfect ray of sunlight provides enough heat to help it momentarily prosper. But even for the toughest of microbes, Mount Everest is a Hotel California: “You can check out any time you like/ But you can never leave.”

    The researchers don’t expect this microscopic impact on Everest to significantly affect the broader environment. But this work does carry implications for the potential for life far beyond Earth, if one day humans step foot on Mars or beyond.

    “We might find life on other planets and cold moons,” said Schmidt. “We’ll have to be careful to make sure we’re not contaminating them with our own.”

    Additional authors on this publication include: Anton Seimon, Department of Geography and Planning, Appalachian State University; and Tracie Seimon, Wildlife Conservation Society, Zoological Health Program, Bronx, New York.

    This work was supported by the National Geographic and Rolex Perpetual Planet Everest Expedition, the Department of Ecology and Evolutionary Biology, and the University of Colorado Boulder Libraries Open Access Fund.

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  • Microbes can create a more peaceful world: Scientists call to action

    Microbes can create a more peaceful world: Scientists call to action

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    Newswise — Microorganisms should be ‘weaponised’ to stave off conflicts across the globe, according to a team of eminent microbiologists. 

    The paper ‘Weaponising microbes for peace’ by Anand et al, outlines the ways in which microbes and microbial technologies can be used to tackle global and local challenges that could otherwise lead to conflict, but warns that these resources have been severely underexploited to date. 

    Professor Kenneth Timmis, Founding Editor of AMI journals Environmental Microbiology, Environmental Microbiology Reports and Microbial Biotechnology, says that worldwide deficits and asymmetries in basic resources and services considered to be human rights, such as drinking water, sanitation, healthy nutrition, access to basic healthcare and a clean environment, can lead to competition between peoples for limited resources, tensions, and in some cases conflicts. 

    “There is an urgent need to reduce such deficits, to level up, and to assure provision of basic resources for all peoples. This will also remove some of the causes of conflicts. There is a wide range of powerful microbial technologies that can provide or contribute to this provision of such resources and services, but deployment of such technologies is seriously underexploited,” Professor Timmis said. 

    The paper then lists a series of ways in which microbial technologies can contribute to challenges such as food supply and security, sanitation and hygiene, healthcare, pollution, energy and heating, and mass migrations and overcrowding. For example, microbes are at the core of efforts to tackle pollution by bioremediation, replacing chemical methods of treating drinking water with metalloid conversion systems, and producing biofuels from wastes. 

    “There is now a desperate need for a determined effort by all relevant actors to widely deploy appropriate microbial technologies to reduce key deficits and asymmetries, particularly among the most vulnerable populations,” Professor Timmis said..  

    “Not only will this contribute to the improvement of humanitarian conditions and levelling up, and thereby to a reduction in tensions that may lead to conflicts, but also advance progress towards attainment of Sustainable Development Goals,” he said. . 

    “In this paper, we draw attention to the wide range of powerful microbial technologies that can be deployed for this purpose and how sustainability can be addressed at the same time. We must weaponise microbes for peace.”

    RECOMMENDED ACTIONS TO IMPLEMENT RELEVANT MICROBIAL TECHNOLOGY SOLUTIONS TO DEFICITS 

    We need to urgently supply to communities lacking adequate levels of basic resources/services the infrastructure and know-how (capacity building), and funding for 

    1. use of agrobiologics to increase crop yields, by providing green nitrogen, stimulating plant growth, and combatting pathogens and pests, 

    2. exploitation of plant:microbe partnerships to improve soil health and implement regenerative agriculture, 

    3. creation of nutritious fermented food from locally available crops, 

    4. better use of microbes in the feed and food supply chains, 

    5. production of microbial food for humans and farm animals, 

    6. drinking water production and quality safeguarding, 

    7. waste treatment with resource recovery, 

    8. creation of modular DIY digital medical centres, 

    9. production of vaccines and medicines, 

    10. bioremediation and biorestoration of the environment in general and natural ecosystems in particular, to create healthier habitats and promote biodiversity 

    11. reduction of greenhouse gas production and capturing carbon, 

    12. production of biofuels, 

    13. creation of local employment opportunities associated with the above, 

    14. development of transdisciplinary approaches, using chemistry-related, computation technologies, psychology-related and other approaches that are synergistic to microbial solutions and 

    15. education in societally relevant microbiology 

    ‘Weaponising microbes for peace’ is published in Microbial Biotechnology, an Applied Microbiology International publication, on March 7 2023. 

    The authors are Shailly Anand, John E. Hallsworth, James Timmis, Willy Verstraete, Arturo Casadevall, Juan Luis Ramos, Utkarsh Sood, Roshan Kumar, Princy Hira, Charu Dogra Rawat, Abhilash Kumar, Sukanya Lal, Rup Lal, Kenneth Timmis. 

    To read the full paper, click HERE. 

    To find out more about AMI, visit https://appliedmicrobiology.org/ or https://www.the-microbiologist.com/. 

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  • ‘Gut on a Chip’: New Tech a Big Step Forward for Gut Health

    ‘Gut on a Chip’: New Tech a Big Step Forward for Gut Health

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    March 9, 2023 – From TikTok to kombucha tea, gut health is having a moment – after we’ve already been hearing about it for years. Rightly so. 

    Your gut – and its diverse mix of bacteria known as the microbiome – is no longer just about digestion. Gut “health” is also linked to the health of your heart, brain, immune system, and more.

    The problem: Much about what’s going in in there and what bacteria populate it at what levels – and how to interpret it all – remains a mystery. Studying the gut is tricky. Animal research may not be useful, because animals have different digestive enzymes and gut bacteria than humans do. And typical lab tests, like growing cells in a petri dish, don’t capture how complex the gut is, a part of the body where many types of cells grow and interact in a moist, flowing, oxygen-free environment. 

    An emerging technology, called “gut on a chip,” promises to change all that, opening the door to experiments never before possible and promising to advance medical research, according to a new paper in APL Bioengineering. 

    Your Gut on a Chip

    It’s among the latest advances in “organ on a chip” technology, the concept of putting human cells in a device designed to mimic the activity of human organs. Scientists have developed models to simulate such organs as the lung, kidney, and vagina. 

    To build a gut on a chip, scientists culture cells from gut tissue and bacteria. 

    “These cells don’t grow easily,” says study author Amin Valiei, PhD, a post-doctoral scholar at the University of California, Berkeley. “They need a specific environment.”

    To create that environment, researchers put the cells inside tiny channels designed to allow the flow of fluids and mimic forces found in the gut. That means the cells can interact with each other as they would inside the human body. 

    “These models are getting more and more advanced,” says Valiei. “Compared to a couple years ago, we now have models that can accommodate a few types of cells.”

    Why This Matters: Drugs, Disease, and Dysbiosis

    Researchers can do experiments on the models that would be difficult or impossible in humans. 

    “These devices could be especially useful in the hypothesis stage to test new drugs and therapeutics,” says Valiei. 

    Valiei and his colleagues at UC Berkeley’s Molecular Cell Biomechanics Lab are studying how different bacterial species interact in these gut-chip models. In particular, they’re exploring how certain harmful bacteria can take hold in the gut – a phenomenon known as dysbiosis that’s linked to a range of conditions like inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), diabetes, obesity, cancer, and heart problems.

    Researchers are also using gut-on-a-chip models to study IBD, colorectal cancer, and even the effects of viruses like COVID-19 on gut function. 

    To understand how diseases develop, we need to break things down into fundamental steps, and gut-on-a-chip models could help researchers do that, says Christopher Chang, MD, PhD, a gastroenterologist at the Raymond G. Murphy VA Medical Center in Albuquerque, NM, and the University of New Mexico. (Chang was not involved in the study.) 

    “We can identify literally thousands of species in the gut, and we sort of know, in broad strokes, what microbes are considered beneficial, and what microbes are considered not beneficial,” he says. 

    But how do individual bugs fit into a community? And what combinations lead to a healthy gut versus an unhealthy one? Answers to these questions remain unclear. 

    “We have ways to manipulate the microbiome, through different antibiotics, probiotics, and fecal microbiota transplants,” Chang says. “But we need to know: What should we be manipulating?”

    Room for Improvement

    One part of the gut not yet reflected in gut chip models is the enteric nervous system, aka our “second brain” – neurons embedded in the GI tract, says Chang. This is how the gut and brain communicate, and its dysfunction is linked to bowel disorders such as IBS. 

    People with IBS can have pain, diarrhea, or constipation even though their gut tissue looks normal on biopsies. Gut-on-a-chip models might be less helpful in revealing insights about these disorders, though they could still help answer fundamental questions. 

    The gut-brain connection is still being clarified, so as the science evolves, researchers may be able to add new insights to future gut-on-a-chip models.  

    Gut-on-a-chip models could be useful beyond disease, too, says Valiei. Any medication you swallow goes through your GI tract. If researchers can use gut-on-a-chip models to uncover precisely how we digest and absorb medications, they might be able to refine how we use these drugs.

    For now, the push is on to get this tech into widespread use. Because of the need to do more research, refine the tech, and gather enough data to satisfy regulators, it may still be several years until this kind “precision” medicine will be precise enough to truly personalize its use for patients. But according to Valiei, this is indeed an accurate glimpse of what’s to come.

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  • This Type Of Sugar Could Be Linked To Alzheimer’s Development

    This Type Of Sugar Could Be Linked To Alzheimer’s Development

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    A recent narrative review2 published in the American Journal of Clinical Nutrition explores how the relationship between fructose and humans’ ancient foraging instincts might be to blame for the onset of Alzheimer’s disease (AD).

    Lead author Richard Johnson, M.D., theorizes that because humans evolved to sometimes be quick-thinking risk-takers in the pursuit of food, fructose may actually enhance that instinct by getting in the way of our memory centers and attention to how much time has passed. 

    In other words, a human with less regard for time and recent memory may be more likely to forage for food more quickly and effectively, tending to ignore risk or other distracting factors.

    But as with anything, too much of a good thing can lead to unintended problems.

    “We hypothesized that the fructose-dependent reduction in cerebral metabolism in these regions was initially reversible and meant to be beneficial,” Johnson wrote. “However, the chronic and persistent decrease in cerebral metabolism driven by recurrent fructose metabolism leads to progressive brain atrophy and neuron loss with all of the features of AD.”

    So, this once-lifesaving brain function may be firing too often in the modern brain and leading to permanent damage, leading to diagnoses like AD.

    Scientists noted that wandering off—a common symptom of AD—may even be linked to the foraging instinct promoted in early humans.

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    Jenny Fant

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  • Microbiome disturbances reported as signature of chronic fatigue syndrome/myalgic encephalomyelitis

    Microbiome disturbances reported as signature of chronic fatigue syndrome/myalgic encephalomyelitis

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    Newswise — New research reveals differences in the gut microbiomes of people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) compared to those of healthy controls.

    ME/CFS is characterized by unexplained debilitating fatigue, cognitive dysfunction, gastrointestinal disturbances, among other symptoms.

    The study was led by scientists at the Center for Infection and Immunity (CII) at Columbia University Mailman School of Public Health, as part of the Center for Solutions for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, an inter-disciplinary, inter-institutional research group dedicated to understanding the biology of the disease in order to develop effective means to diagnose, treat and prevent it. Findings appear in the journal Cell Host & Microbe.

    The researchers conducted metagenomic and metabolomic analyses of fecal samples collected from geographically diverse cohort of 106 cases and 91 healthy controls. Results revealed differences in gut microbiome diversity, abundances, functional biological pathways, and interactions between bacteria. Cases and controls were matched for age, sex, geography, and socioeconomic status.

    Gut bacteria Faecalibacterium prausnitzii and Eubacterium rectale, which are both normally abundant and health-promoting, were reduced in ME/CFS participants. For both bacteria, researchers also found a deficient microbial capacity for synthesizing butyrate, the main fuel for the body’s colon cell, with ME/CFS. The abundance of Faecalibacterium prausnitzii was inversely associated with fatigue severity.

    The only other species identified with reduced relative abundance in ME/CFS was C. secundus, an acetate-producer, that could contribute to the net acetate deficiency the researchers found in ME/CFS subjects. Acetate is used by butyrate-producing bacteria to produce butyrate.

    An additional nine species had increased relative abundance in ME/CFS compared to healthy controls, including C. bolteae which in other research has correlated with fatigue in multiple sclerosis. Another, R. gnavus, has been associated with inflammatory bowel disease.

    “The gut microbiome is a complex ecological community teeming with diverse inter-species interactions that can be beneficial or harmful. Our research finds that in people with ME/CFS, there can be extensive rewiring of the networks of bacteria in this system,” says study senior author Brent Williams, PhD, assistant professor of epidemiology in CII at Columbia Mailman School of Public Health.

    “Understanding the connection between ME/CFS and disturbances in the gut microbiome may lead to ways to classify the disease and targets for therapeutic trials,” adds co-author W. Ian Lipkin, MD, CII director and John Snow Professor of Epidemiology at Columbia Mailman School.

    The study’s first author is Cheng Guo, PhD, senior programmer analyst at CII. Additional co-authors are listed in the publication.

    The research was funded by the National Institutes of Health grant to the Center for Solutions for ME/CFS at Columbia University (grant number 1U54AI138370), NIH grant R56AI120724, and anonymous donors through the Crowdfunding Microbe Discovery Project.

    The authors declare no competing interests.

    About ME/CFS

    Experts estimate there are between 800,000 and 2 million Americans with ME/CFS, a complex, debilitating disorder characterized by extreme fatigue after exertion and other symptoms including muscle and joint pain, cognitive dysfunction, sleep disturbance, and orthostatic intolerance. Currently, there is no diagnostic test for the disease; instead, patients are diagnosed based on a clinical examination and history and an exclusion of other disorders.

    Prior Research on ME/CFS

    In a 2017 study, CII scientists reported discovered abnormal levels of specific gut bacteria related to ME/CFS in patients with and without concurrent irritable bowel syndrome, IBS. A year later, another study identified a constellation of metabolites related to ME/CFS, providing the ability to predict whether or not someone has the disorder with a confidence of 84 percent.

    In a 2015 study, CII researchers identified distinct immune changes in patients diagnosed with ME/CFS. These immune signatures represented the first robust physical evidence that ME/CFS is a biological illness as opposed to a psychological disorder, and the first evidence that the disease has distinct stages. In a 2012 study, researchers ruled out a purported link between a mouse retrovirus called XMRV and ME/CFS.

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  • Harmful bacteria can elude predators when in mixed colonies

    Harmful bacteria can elude predators when in mixed colonies

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    Newswise — Efforts to fight disease-causing bacteria by harnessing their natural predators could be undermined when multiple species occupy the same space, according to a study by Dartmouth College researchers.

    When growing in mixed colonies, some harmful bacteria may be able to withstand attacks from the bacteria and viruses that target them by finding protection inside groups of rival species, according to a report published in the Proceedings of the National Academy of Sciences (PNAS).

    The researchers found that the intestinal bacterium Escherichia coli became surrounded by tightly packed colonies of Vibrio cholerae — which causes the deadly disease cholera — when the species were grown together. These clusters protected E. coli from the bacteria Bdellovibrio bacteriovorus that preys on both species individually, but in the study could only kill the outer layer of V. cholerae. This left the unscathed cells of E. coli and V. cholerae insulated within the colonies free to multiply.

    The findings add a new layer of complication to the development of biological antimicrobials, wherein bacteria-killing bacteria or viruses — known as bacteriophages — are deployed to fight infections, said corresponding author Carey Nadell, an assistant professor of biological sciences at Dartmouth College. These organisms can be more effective than antibiotics at penetrating bacterial colonies, or biofilms, and have emerged as a possible supplement or alternative to antibiotics. Bacteria worldwide have become more resistant to antibiotics due to the drugs’ overuse.

    Most research on predatory bacteria and phages, however, has focused on liquid cultures or single-species biofilms, Nadell said. The Dartmouth study shows that the interactions between multiple bacterial species — which are more common in real life — can be difficult to predict from studying species in isolation. , Nadell and coauthors Benjamin Wucher and James Winans, Ph.D. candidates in biological sciences at Dartmouth,In a related study published in the journal PLoS Biology in December found that E. coli also could avoid the bacteriophage T7 when embedded in groups of V. cholerae.

    “There were certain elements of our experiments that are closer to real life — a lot of infections are caused by bacteria living with other bacteria in a biofilm. They’re like a forest — they’re little ecosystems,” Nadell said.

    “For E. coli, if it grew with V. cholerae, it could do better than on its own, but V. cholerae did worse. It’s fascinating that growing together had opposite effects on each species’ chances of survival,” he said. “Our research shows that the way prey populations can resist or not resist predators can be very different in multispecies conditions. The efficacy of bacteriophages and predatory bacteria to kill off harmful bacteria might depend on the other species their prey are living with, and on the biofilm structures they produce alone versus together.”

    In the PNAS study, the protection afforded E. coli depended on how close the two bacteria were when they began growing. When sparsely populated, V. cholerae had ample room to form into tightly packed colonies that would encase E. coli, which does not grow as densely.

    But when both species started out close together, E. coli prevented V. cholerae from producing its normal group structure. This disruption caused both species to become more vulnerable to death by B. bacteriovorus.

    “When we put these species together, we observed biofilm properties we could not really predict from each alone that would have direct implications on the use of phages and predatory bacteria to kill them,” Nadell said. “Our work highlights the importance of studying other examples of multispecies biofilm structures. We feel confident that what we saw will apply to other cases, but it’s a question of when and to what extent.”

    The paper, “Breakdown of Clonal Cooperative Architecture in Multispecies Biofilms and the Spatial Ecology of Predation,” was published online by the Proceedings of the National Academy of Sciences DATE. The work was supported by the National Science Foundation (IOS 2017879 and MCB 1817352), the Simons Foundation (826672), the Human Frontier Science Program (RGY0077/2020), and a Gillman Fellowship and GAANN Fellowship from the Dartmouth College Department of Biological Sciences.

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  • Discovering Unique Microbes Made Easy with DOE Systems Biology Knowledgebase (KBase)

    Discovering Unique Microbes Made Easy with DOE Systems Biology Knowledgebase (KBase)

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    The Science

    Microbes are foundational for life on Earth. These tiny organisms play a major role in everything from transforming sunlight into the fundamental molecules of life. They help to produce much of the oxygen in our atmosphere. They even cycle nutrients between air and soil. Scientists are constantly finding interactions between microbes and plants, animals, and other macroscopic lifeforms. As genomic sequencing has advanced, researchers can investigate not only isolated microbes, but also whole communities of microorganisms – known as microbiomes – based on DNA found in an environment. The genomes extracted from these communities (metagenomic sequences) can identify the organisms that carry out biogeochemical processes, contribute to health or disease in human gastrointestinal microbiomes, or interact with plant roots in the rhizosphere. The Department of Energy Systems Biology Knowledgebase (KBase) recently released a suite of features and a protocol for performing sophisticated microbiome analysis that can accelerate research in microbial ecology.

    The Impact

    The widespread adoption of DNA sequencing in microbiology has generated huge amounts of genomic data. Researchers need computational tools to recover high-quality genomes from environmental samples to understand which organisms live in an environment and how they might interact. The combination of usability, data, and bioinformatics tools in a public online resource makes KBase a uniquely powerful web platform for performing this task. These new features in KBase will allow biologists to obtain genomes from microbiome sequences with easy-to-use software powered by Department of Energy computational resources. This will reduce the time required to process sequencing data and characterize genomes. Scientists can use KBase to collaboratively analyze genomics data and build research communities to solve common problems in microbial ecology.

    Summary

    Obtaining genomes of uncultivated microbes directly from the environment using DNA sequencing is a recent advance that allows scientists to discover and characterize novel organisms. Sequencing the DNA of all the microbes in a given environment produces a “metagenome.” Performing genetic analysis of metagenomes has emerged as a way to explore microbial traits and behaviors and community interactions in an environmental context. Methods for obtaining metagenome-assembled genomes (MAGs) have varying degrees of success, depending on the techniques used. An increasing number of researchers generate microbiome sequences, but many do not have ready access to the expertise, tools, and computational resources necessary to extract, evaluate, and analyze their genomes.

    The KBase team added and updated several metagenome analysis tools, data types, and execution capabilities to provide researchers the tools that accelerate the discovery of microbial genomes and uncover the genetic potential of microbial communities. A recent paper in Nature Protocols presents a series of analysis steps, using KBase apps and data products for extracting high quality MAGs from metagenomes. These capabilities, including computing, data storage, and sharing of data and analyses, are provided free to the public via the KBase web platform. This protocol allows scientists to both generate putative genomes from organisms only found in the environment and analyze them with tools to understand who they are, what they are doing, who they are interacting with, and their role in the ecosystem.

     

    Funding

    KBase is funded by the Genomic Science Program in the Department of Energy Office of Science, Office of Biological and Environmental Research.


    Journal Link: Nature Protocols

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    Department of Energy, Office of Science

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  • Turning a poison into food

    Turning a poison into food

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    Newswise — Methanogens are microorganisms that produce methane when little or no oxygen is present in their surroundings. Their methane production – for example in the digestive tract of ruminants – is relevant for global carbon cycling, as methane is a very potent greenhouse gas, but can also be used as an energy source to heat our houses.

    A toxic base for growth

    The object of the study now published in Nature Chemical Biology are two marine heat-loving methanogens: Methanothermococcus thermolithotrophicus (lives in geothermally heated sediments at around 65 °C) and Methanocaldococcus jannaschii (prefers deep-sea volcanos with around 85 °C). They obtain their cellular energy by producing methane and receive sulfur for growth in form of sulfide, that is present in their environments.  While sulfide is a poison for most organisms, it is essential for methanogens and they can tolerate even high concentrations of it. However, their Achilles’ heel is the toxic and reactive sulfur compound sulfite, which destroys the enzyme needed to make methane. In their environments, both investigated organisms are occasionally exposed to sulfite, for example, when oxygen enters and reacts with the reduced sulfide. Its partial oxidation results in the formation of sulfite, and thus the methanogens need to protect themselves. But how can they do this?

    A molecular snapshot of the process

    Marion Jespersen and Tristan Wagner from the Max Planck Institute for Marine Microbiology in Bremen, Germany, together with Antonio Pierik from the University of Kaiserslautern, now provide a snapshot of the enzyme detoxifying the sulfite. This butterfly-shaped enzyme ist known as the F420-dependent sulfite reductase or Fsr. It is capable of turning sulfite into sulfide – a safe source of sulfur that the methanogens require for growth. In the current study, Jespersen and her colleagues describe how the enzyme works. “The enzyme traps the sulfite and directly reduces it to sulfide, which can be incorporated, for example, into amino acids”, Jespersen explains (see figure). “As a result, the methanogen doesn’t get poisoned and even uses the product as its sulfur source. They turn poison into food!”

    It sounds simple. But in fact, Jespersen and her colleagues found that they were dealing with a fascinating and complicated overlap. “There are two ways of sulfite reduction: dissimilatory and assimilatory”, Jespersen explains. “The organism under study uses an enzyme that is built like a dissimilatory one, but it uses an assimilatory mechanism. It combines the best of both worlds, one could say, at least for its living conditions.”

    It is assumed that the enzymes from both the dissimilatory and the assimilatory pathway have evolved from one common ancestor. “Sulfite reductases are ancient enzymes that have a major impact on the global sulfur and carbon cycles”, adds Tristan Wagner, head of the Max Planck Research Group Microbial Metabolism at the Max Planck Institute in Bremen. “Our enzyme, the Fsr, is probably a snapshot of this ancient primordial enzyme, an exciting look back in evolution.”

    Biotechnological applications in view

    The Fsr not only opens up evolutionary implications but also allows us to better understand the fascinating world of marine microbes. Methanogens that can grow only on sulfite circumvent the need to use the dangerous sulfide, their usual sulfur substrate. “This opens opportunities for safer biotechnological applications to study these important microorganisms. An optimal solution would be to find a methanogen that reduces sulfate, which is cheap, abundant, and a completely safe sulfur source”, says Wagner. In fact, this methanogen already exists, it is Methanothermococcus thermolithotrophicus. The researchers hypothesized that Fsr orchestrates the last reaction of this sulfate reduction pathway, because one of its intermediates would be sulfite. “Our next challenge is to understand how it can transform sulfate to sulfite, to get a complete picture of the capabilities of these miracle microbes.”

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    Max Planck Institute for Marine Microbiology

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  • Deep meditation may alter gut microbes for better health

    Deep meditation may alter gut microbes for better health

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    Newswise — Regular deep meditation, practised for several years, may help to regulate the gut microbiome and potentially lower the risks of physical and mental ill health, finds a small comparative study published in the open access journal General Psychiatry.

    The gut microbes found in a group of Tibetan Buddhist monks differed substantially from those of their secular neighbours, and have been linked to a lower risk of anxiety, depression, and cardiovascular disease.

    Research shows that the gut microbiome can affect mood and behaviour through the gut–brain axis. This includes the body’s immune response, hormonal signalling, stress response and the vagus nerve—the main component of the parasympathetic nervous system, which oversees an array of crucial bodily functions.

    The significance of the group and specimen design is that these deep-thinking Tibetan monks can serve as representatives of some deeper meditations. Although the number of samples is small, they are rare because of their geographical location.

    Meditation is increasingly being used to help treat mental health disorders, such as depression, anxiety, substance abuse, traumatic stress, and eating disorders as well as chronic pain. But it’s not clear if it might also be able to alter the composition of the gut microbiome, say the researchers.

    In a bid to find out, the researchers analysed the stool and blood samples of 37 Tibetan Buddhist monks from three temples and 19 secular residents in the neighbouring areas.

    Tibetan Buddhist meditation originates from the ancient Indian medical system known as Ayurveda, and is a form of psychological training, say the researchers. The monks in this study had been practising it for at least 2 hours a day for between 3 and 30 years.

    None of the participants had used agents that can alter the volume and diversity of gut microbes: antibiotics; probiotics; prebiotics; or antifungal drugs in the preceding 3 months.

    Both groups were matched for age, blood pressure, heart rate, and diet.

    Stool sample analysis revealed significant differences in the diversity and volume of microbes between the monks and their neighbours. 

    Bacteroidetes and Firmicutes species were dominant in both groups, as would be expected. But Bacteroidetes were significantly enriched in the monks’ stool samples (29% vs 4%), which also contained abundant Prevotella (42% vs 6%) and a high volume of Megamonas and Faecalibacterium.

    “Collectively, several bacteria enriched in the meditation group [have been] associated with the alleviation of mental illness, suggesting that meditation can influence certain bacteria that may have a role in mental health,” write the researchers.

    These include Prevotella, Bacteroidetes, Megamonas and Faecalibacterium species, the previously published research suggests.

    The researchers then applied an advanced analytical technique to predict which chemical processes the microbes might be influencing. This indicated that several protective anti-inflammatory pathways, in addition to metabolism—the conversion of food into energy—were enhanced in the meditation people.

    Finally, blood sample analysis showed that levels of agents associated with a heightened risk of cardiovascular disease, including total cholesterol and apolipoprotein B, were significantly lower in the monks than in their secular neighbours by their functional analysis with the gut microbes.

    Although a comparative study, it is observational and the numbers of participants were small, all male, and lived at high altitude, making it difficult to draw any firm or generalisable conclusions. And the potential health implications could only be inferred from previously published research.

    But based on their findings, the researchers suggest that the role of meditation in helping to prevent or treat psychosomatic illness definitely merits further research.

    And they conclude: “These results suggest that long-term deep meditation may have a beneficial effect on gut microbiota, enabling the body to maintain an optimal state of health.”

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    BMJ

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  • ‘Lights out’ for antibiotic-resistant superbugs

    ‘Lights out’ for antibiotic-resistant superbugs

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    Newswise — It’s ‘lights out’ for antibiotic-resistant superbugs as next-generation light-activated nanotech proves it can eradicate some of the most notorious and potentially deadly bacteria in the world.

    Developed by the University of South Australia and published in Pharmaceutics, the new light therapy can eliminate antibiotic-resistant superbugs golden staph and pseudomonas aeruginosa by 500,000-fold and 100,000-fold respectively.

    Golden staph (staphylococcus aureus) and pseudomonas aeruginosa are among the most deadly superbugs in the world. Globally, about 1.27 million people die as a result of antibiotic-resistant bacteria.

    Lead researcher, UniSA’s Dr Muhammed Awad, says the new light therapy will be a game-changer for millions of people worldwide.

    “Golden staph and pseudomonas aeruginosa are both highly transmissible bacteria, commonly found on people’s skin. But if they get into the blood, they can lead to sepsis or even death,” Dr Awad says.

    “Patients in hospitals – particularly those with wounds or catheters, or those on ventilators – have a higher risk of getting these bacteria, and while antibiotics may help, their extensive use has led to waves of microbial resistance, often making them ineffective.

    “Our photodynamic technology works differently, harnessing the energy of light to generate highly reactive oxygen molecules that eradicate microbial cells and kill deadly bacteria, without harming human cells.”

    The researchers tested the antimicrobial photodynamic therapy on recalcitrant bacterial infections caused by antibiotic resistant strains of golden staph and pseudomonas aeruginosa.

    Senior researcher, UniSA’s Professor Clive Prestidge, says that the technology has some key advantages over conventional antibiotics and other light therapies.

    “The new therapy is created in an oil that that is painted on a wound as a lotion. When laser light is applied to the lotion, it creates reactive oxygen species which act as an alternative to conventional antibiotics,” Prof Prestidge says.

    “Current photoactive compounds also suffer from poor water-solubility which mean that they have limited clinical application.

    “Our approach uses food grade lipids to construct nanocarriers for the photoactive compound which improves its solubility and antibacterial efficiency far beyond that of an unformulated compound.

    “These molecules target multiple bacterial cells at once, preventing bacteria from adapting and becoming resistant. So, it’s a far more effective and robust treatment.

    “Importantly, the human skin cells involved in the wound healing process showed enhanced viability, while the antibiotic resistant bacteria were entirely eradicated.”

    The consequences of not managing superbugs are high. Already, antibiotic resistant microbials cost millions of lives and trillions of dollars to the global economy each year.

    “This technology is very promising and is gaining the attention of scientists worldwide,” Prof Prestidge says.

    “The next step is to commence clinical trials and develop this technology further to be available in clinics. With the support of funding bodies, we hope that Australians will have access to this technology as soon as possible.”

     

    Notes to editors:

    Multiple papers are available upon request: 

    …………………………………………………………………………………………………………………………

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    University of South Australia

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  • Mayo Clinic researchers link ovarian cancer to bacteria colonization in microbiome

    Mayo Clinic researchers link ovarian cancer to bacteria colonization in microbiome

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    Newswise — ROCHESTER, Minn. — A specific colonization of microbes in the reproductive tract is commonly found in women with ovarian cancer, according to a new study from Mayo Clinic’s Center for Individualized Medicine. The discovery, published in Scientific Reports, strengthens evidence that the bacterial component of the microbiome — a community of microorganisms that also consists of viruses, yeasts and fungi — is an important indicator for early detection, diagnosis and prognosis of ovarian cancer.

    “In addition, we found a clear pattern that reveals women with early stage ovarian cancer have a significantly higher accumulation of the pathogenic microbes when compared to women with later-stage disease,” says Abigail Asangba, Ph.D., a microbiome researcher within the Center for Individualized Medicine. “In later stages, the number of microbes fades. This strong signal could potentially help us diagnose women earlier and save lives — similar to how a noninvasive Pap smear is used to detect cervical cancer.”

    The study also suggests that a higher accumulation of pathogenic microbes plays a role in treatment outcomes and could be a potential indicator for predicting a patient’s prognosis and response to therapy.

    “We analyzed whether patients with similar outcomes also had a similar microbial composition before they started treatment, irrespective of stage, grade or histology of cancer, as well as other factors,” Dr. Asangba says. “And we found that the patients with a higher accumulation of pathogenic microbes had poorer outcomes in comparison to those without.” 

    Ovarian cancer ranks fifth in cancer deaths among women and is the second most common gynecological malignancy. An estimated 20,000 women in the U.S. are expected to be diagnosed with ovarian cancer in 2023, and nearly 13,000 will die from the disease, according to the American Cancer Society. Most women who are affected are usually diagnosed at an advanced stage because early-stage disease is usually asymptomatic. Furthermore, only 20% of cases are caused by genetic mutations, including BRCA1 and BRCA2 genes, while the remaining 80% of cases have no known cause.

    Zeroing in on pathogenic microbes

    For the study, the researchers investigated samples of 30 women undergoing a hysterectomy for ovarian cancer and compared them to samples of 34 women undergoing a hysterectomy for a benign condition. They used high-throughput sequencing to analyze the samples, which were recovered from the lower and upper reproductive tract, peritoneal fluid, urine, and anal microbiome.

    In the women with ovarian cancer, the team observed a colonization of disease-causing bacteria, including Dialister, Corynebacterium, Prevotella and Peptoniphilus.

    “These microbes are known to be associated with other diseases, including other cancers, but more study is needed to know if they are a contributing driver of ovarian cancer,” says Marina Walther-Antonio, Ph.D., a microbiome researcher within Mayo Clinic’s Center for Individualized Medicine and a study author. Dr. Walther-Antonio is a member of the Mayo Clinic Comprehensive Cancer Center. She focuses on women’s health, particularly gynecologic cancers.

    “Our ultimate goal is to understand what role the microbiome plays in gynecologic cancers. We are exploring several potential avenues: the role in the causation of the disease, aggravation of the disease and treatment resistance,” Dr. Walther-Antonio says. 

    The study is an extension of several other previously published studies by Dr. Walther-Antonio and her team that link the microbiome to endometrial cancer. In one study, the team found that a microbe called Porphyromonas somerae has a pathogenic role in endometrial cancer via intracellular activity. 

    Dr. Walther-Antonio says identifying microbiome signatures to predict the development of malignancies could lead to intervention before cancers have a chance to materialize.

    “Our latest study provides a significant leap toward understanding the prognostic potential of the microbiome and places us a step closer to being able to help our patients,” Dr. Walther-Antonio says.

    Acknowledgements

    This work was supported by a career development award from the Mayo Clinic Ovarian SPORE National Institutes of Health grant P50 CA136393), the Minnesota Ovarian Cancer Alliance and CTSA grant KL2TR002379 from the National Center for Advancing Translational Sciences.

    ###

    About Mayo Clinic Comprehensive Cancer Center
    Designated as a comprehensive cancer center by the National Cancer Institute, Mayo Clinic Comprehensive Cancer Center is defining new boundaries in possibility, focusing on patient-centered care, developing novel treatments, training future generations of cancer experts, and bringing cancer research to communities. At Mayo Clinic Comprehensive Cancer Center, a culture of innovation and collaboration is driving research breakthroughs that are changing approaches to cancer prevention, screening and treatment, and improving the lives of cancer survivors.

    About Mayo Clinic 
    Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

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    Mayo Clinic

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  • How To Whiten Your Teeth At Home + What To Avoid, From Dentists

    How To Whiten Your Teeth At Home + What To Avoid, From Dentists

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    First things first, you’ll want to write down a list of possible lifestyle habits that could be discoloring your teeth. For the most part, this falls into two categories: Food and dental hygiene habits. 

    “Coffee, tea, red wine, sodas, and tobacco use are the most common culprits for yellowing teeth,” dentist and founder of Walden Dental David Frank, DMD tells mbg. But if you skip a basic oral care routine—including brushing, flossing, and possibly a mouthwash, there’s no way your teeth will stay perfectly white. 

    Other possible factors contributing to teeth discoloration include aging, genetics, and oral trauma, dentist and founder of oral care brand GLO Science Jonathan B. Levine, DMD tells mbg. 

    In addition, some medications can cause tooth discoloration. “Antihistamines, antipsychotics, and blood pressure medications can cause dry mouth, which can lead to tooth decay and yellowing of the teeth,” Levine says. 

    These factors can be harder to spot and control, so meet with your dentist if you think any of the above may apply to you. Regardless, start with the habits you can control. 

    Once you’ve evaluated what might be causing your teeth to yellow in the first place, do your best to either moderate or eliminate the habit if possible. If you’re concerned about coffee (this one’s arguably the most common), consider opting for a reusable straw to ensure the coffee doesn’t touch your front teeth, or carry a travel-friendly toothbrush with you for a quick cleaning post-coffee.

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    Hannah Frye

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