Tag: Microbiome

Single Cell Protein: an alternative eco-friendly protein source derived from microorganisms

Newswise — Researchers and businesses are increasingly drawn to alternative protein sources as they grapple with the challenge of meeting the growing global demand for protein. Among the unconventional sources, microorganisms stand out for their remarkable protein content.

Dry microorganism cells have been described as “single cell protein” (SCP) or “microbial protein”. SCP is primarily sourced from microorganisms such as yeasts, fungi, bacteria and algae. They serve as an environmentally friendly alternative to animal-derived proteins. Furthermore, microorganisms exhibit the capacity to thrive on a diverse range of substrates for their growth, including waste materials. Leveraging renewable resources derived from different waste streams within the food and agricultural sector, such as dairy waste, crop residues, sugar industry byproducts, and fruit waste, has the potential to greatly enhance SCP production from a standpoint of socio-economic and environmental sustainability.

“Particularly when SCP production is integrated into biorefinery frameworks, it can significantly advance circular bio-economy concepts, fostering the continued growth of the SCP market for applications in animal feed, innovative food formulations, and bioactive food packaging,” explains Danai Ioanna Koukoumaki, first author of a recent review on the topic published in Carbon Resources Conversion.

“It’s true that the use of microorganisms for protein production holds promise, but it is nonetheless crucial to study consumer perceptions of this alternative protein source,” adds Koukoumaki, who is a PhD candidate at the Department of Food Science and Nutrition, University of the Aegean.

For instance, in a research study examining the attitudes of older adults towards alternative protein sources such as single-cell protein and plant-based protein, it was observed that gender and country of residence had a notable impact on acceptance levels.

Overall, the review provides a clear insight of the micro-organisms, agro-industrial wastes, functional properties, as well as current applications of single-cell protein.

“Utilizing renewable feedstock in SCP production has the potential to address both modern society’s challenges of food waste management and protein shortages. However, to effectively commercialize this alternative, efforts must be made to enhance consumer acceptance,” concludes corresponding author Dimitris Sarris.

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References

DOI

10.1016/j.crcon.2023.07.004

Original Source URL

https://doi.org/10.1016/j.crcon.2023.07.004

Funding information

This research was funded by the project “Infrastructure of Microbiome Applications in Food Systems-FOODBIOMES” (MIS 5047291), which is implemented under the Action “Regional Excellence in R&D Infrastructures”, funded by the Operational Programme “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014-2020) and co-financed by Greece and the European Union (European Regional Development Fund).

Journal

Carbon Resources Conversion

Chinese Academy of Sciences

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September 23, 2023
New Grant to Optimize Gut Microbes, Boost Health Benefits of Broccoli

BYLINE: Lauren Quinn

Newswise — URBANA, Ill. — Love it or hate it, broccoli is chock-full of health-promoting chemicals linked to heart health, cancer prevention, immune function, weight management, and more. However, some people are less efficient than others at unlocking those chemical benefits. A research team at the University of Illinois Urbana-Champaign suggests gut microbe communities may be responsible for the variation. With a new grant from the USDA’s National Institute of Food and Agriculture, the team plans to identify which microbes maximize the benefits of broccoli and other brassica vegetables.

Gut microbes only factor in when we eat cooked broccoli. When eating the vegetable raw, healthy compounds — and a bitter taste — are unleashed with every gnash of our teeth, the result of a chemical reaction activated by physical damage. Eliminating the bitterness is easy; we just have to cook it. But cooking inactivates the enzyme involved in the reaction, myrosinase. Thankfully, some microbes manufacture their own version of myrosinase, making it possible for them to complete the reaction in the gut with varying levels of efficiency.

“Gut bacteria can metabolize glucosinolates in broccoli to isothiocyanates (ITCs), the bioactive compounds with known health benefits, but they can also break glucosinolates into other inactive materials that do nothing for us. We’re focusing on the flux between these metabolic outcomes and how we can potentially steer that flux towards ITCs and away from the non-bioactive products,” said Michael Miller, principal investigator of the grant and professor in the Department of Food Science and Human Nutrition, part of the College of Agricultural, Consumer and Environmental Sciences (ACES) at U. of I.

The first step is identifying which bacteria are involved and how efficiently they produce ITCs versus non-beneficial compounds. Miller’s team has a study underway in mice, a model system that can provide clues for future human studies. He is feeding the mice broccoli and kale, both cooked and uncooked, to understand the chemical and microbial dynamics of the system.

Once ITCs are unlocked — whether in the mouth or the gut — they trigger bitter-taste receptors in cell membranes, starting a series of reactions that produce hormones affecting glucose homeostasis and the perception of fullness.

“We actually have bitter taste receptors all the way down, not just in our mouths, but in our colon and small intestine, too,” Miller said. “The goal of our work is to show that the bitter compounds (ITCs) made by gut bacteria from metabolizing broccoli trigger bitter taste receptors in the gut and impact satiety, causing mice to eat less.”

Once he identifies bacterial superstars that maximize ITC production for anti-cancer and weight management benefits, Miller says custom probiotics could be developed to help level the playing field for people with lower-efficiency microbial communities. He also predicts his research will inform recommendations about whether raw or cooked broccoli (or kale) might be more useful for weight loss.

College of Agricultural, Consumer and Environmental Sciences, University of Illinois Urbana-Champaign

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August 31, 2023
Unveiling the Deceptive Tactics of Herpes Virus HCMV in Host Cells

Newswise — Herpes viruses are treacherous: once you are infected, you can never get rid of the virus. This is because herpes viruses lie dormant in certain host cells in the body for a lifetime. Almost every adult unknowingly carries at least one of the nine different human herpes viruses. The virus can be reactivated due to age, stress or a weakened immune system and lead to sometimes severe diseases.

Herpes viruses are so successful because they have adapted well to humans and developed effective strategies to escape the immune system. Proteins that make the infected cell believe that it is not infected or threatened play a central role in camouflage. It is known, for example, that every herpes virus has a powerful proteome, i.e. a large number of these proteins, which, highly adapted to the host, enables it to replicate efficiently immediately after infection. The complex proteome also ensures that multilayered particles are built up in the already infected cell. These newly formed viruses – also called virions – contain numerous viral proteins as well as host proteins. In the center of the particles is the viral DNA, which is enclosed by a nucleocapsid. A layer of numerous other proteins called tegument is formed around this capsid.

Particles come into play in the reactivation of the virus

The particles are crucial in enabling the virus to replicate again and spread systemically in the body after reactivation triggered by whatever means. They are therefore central to the outbreak of disease – after a long period of dormancy (latency).

However, little is known about the internal organization of these particles, especially the protein-protein interactions within the tegument. Researchers from the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) and the Charité–Universitätsmedizin Berlin have therefore taken a closer look at the particles, specifically in human cytomegalovirus (HCMV). HCMV occurs particularly frequently in the population and can be really dangerous, especially for transplant recipients and unborn children who become infected via the mother. Despite intensive research, there is currently no well-tolerated antiviral therapy that could effectively control or even eliminate the virus. There is also no vaccination against this type of virus.

Map shows which proteins interact with each other

In the current work, the team led by Fan Liu (FMP) and Lüder Wiebusch (Charité) has for the first time created a detailed map of the spatial interactions between viral and host cell proteins within HCMV particles. Among other things, this revealed that certain host cell proteins are recruited by viral proteins and play a role in viral replication. For example, a viral protein called UL32 recruits a cellular protein (protein phosphatase , PP1) into the particle to avoid binding of other, unwanted, host cell proteins.

“HCMV itself does not have any phosphatases like PP1, so you can see that the virus takes advantage of certain host cell proteins to replicate efficiently,” says FMP virologist Boris Bogdanow, explaining a key strategy for how HCMV tricks its host.

To study the interactions between the different proteins in intact HCMV particles layer by layer, the researchers used a technique called cross-linking mass spectrometry. “This method also allows us to draw conclusions about the identity of the proteins,” emphasized Fan Liu, an expert in mass spectrometry at the FMP. “But what is special and unique about cross-linking is that we can see which proteins interact with each other and where.”

Never before has this innovative technology been used to map the spatial organization of interactions within herpesviral particles. With the data thus obtained, a computer model of the HCMV particle was subsequently created at FU Berlin by Mohsen Sadeghi. The virtual model allows simulation of each protein within the particle and visualizes the biophysical processes in a vivid way.

“The identified protein-protein interaction is important to better understand the complex life cycle of HCMV,” Boris Bogdanow classifies the results. “And this, in turn, is important for finding candidate anti-viral drugs against HCMV.”

Leibniz-Forschungsinstitut fur Molekulare Pharmakologie

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August 7, 2023
Rapid Adaptation of Acinetobacter baumannii to Novel Environments

Newswise — FRANKFURT. Each year, over 670,000 people in Europe fall ill because of antibiotic-resistant pathogens, and 33,000 die from the infections. Especially feared are pathogens with resistances against multiple, or even all, known antibiotics. One of these is the bacterium Acinetobacter baumannii, feared today above all as the “hospital superbug”: According to estimates, up to five percent of all hospital-acquired and one tenth of all bacterial infections resulting in death can be attributed to this pathogen alone. This puts A. baumannii right at the top of a list of pathogens for which – according to the World Health Organization (WHO) – there is an urgent need to develop new therapies.

Understanding which characteristics make A. baumannii a pathogen is one of the prerequisites for this. To this end, bioinformaticians led by Professor Ingo Ebersberger of Goethe University Frankfurt and the LOEWE Center for Translational Biodiversity Genomics (LOEWE-TBG) are comparing the genomes and the proteins encoded therein across a wide range of different Acinetobacter strains. Conclusions about which genes contribute to pathogenicity can be drawn above all from the differences between dangerous and harmless strains.

Due to a lack of suitable methods, corresponding studies have so far concentrated on whether a gene is present in a bacterial strain or not. However, this neglects the fact that bacteria can acquire new characteristics by modifying existing genes and thus also the proteins encoded by them. That is why Ebersberger’s team has developed a bioinformatics method to track the modification of proteins along an evolutionary lineage and has now applied this method for the first time to Acinetobacter in collaboration with microbiologists from the Institute for Molecular Biosciences and the Institute of Medical Microbiology and Infection Control at Goethe University Frankfurt.

In the process, the researchers concentrated on hair-like cell appendages, known as type IVa (T4A) pili, which are prevalent in bacteria and that they use to interact with their environment. The fact that they are present in harmless bacteria on the one hand and have even been identified as a key factor for the virulence of some pathogens on the other suggests that the T4A pili have repeatedly acquired new characteristics associated with pathogenicity during evolution.

The research team could show that the protein ComC, which sits on the tip of the T4A pili and is essential for their function, shows conspicuous changes within the group of pathogenic Acinetobacter strains. Even different strains of A. baumannii have different variants of this protein. This leads bioinformatician Ebersberger to compare the T4A pili to a multifunctional garden tool, where the handle is always the same, but the attachments are interchangeable. “In this way, drastic functional modifications can be achieved over short evolutionary time spans,” Ebersberger is convinced. “We assume that bacterial strains that differ in terms of their T4A pili also interact differently with their environment. This might determine, for example, in which corner of the human body the pathogen settles.”

The aim is to use this knowledge of the unexpectedly high diversity within the pathogen to improve the treatment of A. baumannii infections, as Ebersberger explains: “Building on our results, it might be possible to develop personalized therapies that are tailored to a specific strain of the pathogen.” However, the study by Ebersberger and his colleagues also reveals something else: Previous studies on the comparative genomics of A. baumannii have presumably only unveiled the tip of the iceberg. “Our approach has gone a long way towards resolving the search for possible components that characterize pathogens,” says Ebersberger.

https://aktuelles.uni-frankfurt.de/english/how-the-hospital-pathogen-acinetobacter-baumannii-quickly-adapts-to-new-environmental-conditions/

Goethe-Universitat Frankfurt am Main

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August 7, 2023
Novel Metric Examines the Role of Organic Matter and Microbes in Ecological Communities

The Science

Ecological researchers study the relationships among different organisms and between organisms and their surroundings. This makes it critical to understand how individual features in a community, like microbes or types of chemicals, affect the overall community’s development. By examining individual features, researchers can begin to identify those community or assemblage members that drive similarities across communities. To assist in this goal, scientists developed a novel ecological metric, called βNTIfeat. Many microbes do not grow in laboratory conditions. The new metric found that these “unculturable” microbes shape the microbial communities in river corridors. The metric also revealed that organic matter is influenced by a variety of compounds that contain nitrogen and phosphorus.

The Impact

βNTIfeat will help researchers answer longstanding questions about ecosystems. For example, βNTIfeat can help uncover a common group of microbes that significantly affect various river corridors at different local or global scales. This will allow researchers to incorporate the dynamics of these microbes into models. In turn, these models will help scientists to generate predictions about how ecosystems may change due to climate change, wildfires, and other future disturbances.

Summary

Evaluating how ecological communities develop and change is one of the primary goals of ecology. By examining processes that give rise to specific community configurations across varied conditions, researchers will have a better understanding of the fundamental principles that govern community structure and will be able to improve predictions. Unfortunately, comparatively few studies examine the effects that individual features within a community or assemblage play on its overall structure. As part of this study, researchers from Pacific Northwest National Laboratory and California Lutheran University developed a new metric, called βNTIfeat, that investigates the contributions that these features make within a community.

Researchers used βNTIfeat to evaluate feature-level ecological processes in a riverine ecosystem to reveal some key dynamics. First, the team observed that unclassified and unculturable microbial lineages often contribute to differences across the microbial communities; this observation suggests that these unclassified/uncultured lineages play an outsized role relative to their abundance. Secondly, the organic matter assemblages were often driven by nitrogen- and phosphorus-containing molecular formulas, indicating a potential connection to nitrogen/phosphorus-biogeochemical cycles. Finally, by relating the βNTIfeat values for microbes and molecular formulas using a network analysis, researchers determined that members of the microbial family Geobacteraceae often had coordinated contributions to ecological structure with both nitrogen- and phosphorous-containing molecular formulas. This observation suggests there is a complex network of ecological interactions across community types.

Funding

The initial experimental stages of this work were supported by the PREMIS Initiative at the Pacific Northwest National Laboratory (PNNL) with funding from the Laboratory Directed Research and Development Program at PNNL. The later stages of this work (e.g., data analysis, conceptual interpretation manuscript development) were supported by the Department of Energy (DOE) Office of Science, Biological and Environmental Research program, as part of an Early Career Award to James C. Stegen at PNNL. A portion of the research was performed at the Environmental Molecular Sciences Laboratory, a DOE Office of Science user facility at PNNL.

Journal Link: Frontiers in Microbiology, Feb-2022

Department of Energy, Office of Science

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July 28, 2023
New Resource Harmonizes 16S and Shotgun Sequencing Data for Microbiome Research

Newswise — Two leading sequencing techniques are no longer at odds, thanks to an international effort led by scientists at University of California San Diego. In a study published July 27, 2023 in Nature Biotechnology, the researchers debuted a new reference database called Greengenes2, which makes it possible to compare and combine microbiome data derived from either 16S ribosomal RNA gene amplicon (16S) or shotgun metagenomics sequencing techniques.

“This is a significant moment in microbiome research, as we’ve effectively rescued over a decade’s worth of 16S data that might have otherwise become obsolete in the modern world of shotgun sequencing,” said senior author Rob Knight, PhD, professor in the departments of Pediatrics at UC San Diego School of Medicine and Bioengineering and Computer Science at UC San Diego Jacobs School of Engineering. “Standardizing results across these two methods will significantly improve our chances of discovering microbiome biomarkers for health and disease.”

Microbiome studies depend on scientists’ ability to identify which microorganisms are present in a sample. To do this, they sequence the genetic information in the sample and compare it to reference databases that list which sequences belong to which organisms. 16S and shotgun sequencing are the two techniques most widely used in microbiome research, but they often yield different results.

“Many researchers assumed that data from 16S and shotgun sequencing were simply too different to ever be integrated,” said first author of the study Daniel McDonald, PhD, scientific director of The Microsetta Initiative at UC San Diego School of Medicine. “Here we show that is not the case, and provide a reference database that researchers can now use to do just that.”

The original Greengenes database had been widely used in the microbiome field for well over a decade. It was the reference database used by notable projects including the National Institutes of Health Human Microbiome Project, the American Gut Project, the Earth Microbiome Project and many others.

However, one of its fundamental limitations was that it relied on the sequence of a single gene, 16S, to identify the organisms in a sample. This well-studied gene has long been used as a taxonomic marker, with each organism having its own 16S “barcode.” This method can describe the contents of a microbiome sample with genus-level resolution, but it cannot always identify specific species or strains of microbes, which is important for clinical work.

Modern microbiome studies have since transitioned to using shotgun sequencing, which looks at DNA from all over the organisms’ genomes, rather than focusing on only one gene. This powerful approach gives researchers more species-level specificity and also provides insight into the microbes’ function.

Scientists often attributed the discrepancies between the two techniques to differences in the way the samples are prepared in the lab. However, the new study demonstrates that incompatibilities between the two techniques arise from differences in computation, where a better reference database allows for the same conclusions to be drawn from both methods. This addresses an important issue in the reproducibility of microbiome research and allows the re-use of data from millions of samples in older studies.

In trying to resolve these incompatibilities, the researchers first expanded the Web of Life whole genome database. They then used several new computational tools developed with co-author Siavash Mirarab, PhD, associate professor at UC San Diego Jacobs School of Engineering, to integrate existing high-quality full-length 16S sequences into the whole-genome phylogeny. With another machine learning tool developed by Mirarab’s group, they placed 16S fragments from over 300,000 microbiome samples. The result was an expansive reference database that both 16S and shotgun sequencing data could be mapped onto.

To confirm whether Greengenes2 would help standardize findings from either sequencing technique, the researchers acquired both 16S and shotgun sequencing data from the same human microbiome samples and analyzed them both against the backdrop of the Greengenes2 phylogeny. The results from both techniques showed highly correlated diversity assessments, taxonomic profiles and effect sizes — something researchers had not seen before.

“Through Greengenes2, a huge repository of 16S data can now be brought back into the fold and even combined with modern shotgun data in new meta-analyses,” said McDonald. “This is a major step forward in improving the reproducibility of microbiome studies and strengthening physicians’ ability to draw clinical conclusions from microbiome data.”

Co-authors include: Yueyu Jiang, Metin Balaban, Kalen Cantrell, Antonio Gonzalez, Giorgia Nicolaou, Se Jin Song and Andrew Bartko, all at UC San Diego, as well as Qiyun Zhu at Arizona State University, James T. Morton at the National Institutes of Health, Donovan H. Parks and Philip Hugenholtz at The University of Queensland, Søren Karst at Columbia University, Mads Albertsen at Aalborg University, Todd DeSantis at Second Genome, Aki S. Havulinna, Pekka Jousilahti, Teemu Niiranen and Veikko Salomaa at the Finnish Institute for Health and Welfare, Susan Cheng at Brigham and Women’s Hospital and Cedars-Sinai Medical Center, Mike Inouye at University of Cambridge and Baker Heart and Diabetes Institute, Mohit Jain at Sapient Bioanalytics and Leo Lahti at University of Turku.

This work was funded, in part, by the National Science Foundation (grants XSEDE BIO210103 and RAPID 20385.09), the National Institutes of Health (grants 1R35GM142725, U19AG063744, U24DK131617, DP1-AT010885), the Emerald Foundation 3022, Danone Nutricia Research, the Center for Microbiome Innovation and the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

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Disclosures: Rob Knight is a consultant and advisory board member with equity and income in BiomeSense related to the proposed PHS-funded research.

University of California San Diego

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July 27, 2023
Scientists Name Top Five Foods Rich in Prebiotics

Newswise — There is growing evidence that consuming prebiotics — certain types of fiber often found in plants that stimulate beneficial bacteria in your gut — can help to maintain a healthy gut microbiome. In a new study, scientists estimated the prebiotic content of thousands of food types by using preexisting literature to find out which foods offer the highest prebiotic content.

According to the study, foods that pack the greatest prebiotic punch are dandelion greens, Jerusalem artichokes, garlic, leeks, and onions. In addition to supporting gut microbes, prebiotic rich foods contain high amounts of fiber — something most Americans do not get enough of.

“Eating prebiotic dense foods has been indicated by previous research to benefit health,” said Cassandra Boyd, a master’s student at San José State University who conducted the research with Assistant Professor John Gieng, PhD. “Eating in a way to promote microbiome wellness while eating more fiber may be more attainable and accessible than you think.”

Boyd will present the findings at NUTRITION 2023, the flagship annual meeting of the American Society for Nutrition held July 22–25 in Boston.

Prebiotics, which can be thought of as food for the microbiome, are different from probiotics, which contain live microorganisms. Both can potentially benefit microbiome health, but they work in different ways.

Studies have linked higher prebiotic intake with improved blood glucose regulation, better absorption of minerals like calcium, and markers of improved digestive and immune function. Although most dietary guidelines do not currently specify a recommended daily allowance for prebiotics, the International Scientific Association for Probiotics and Prebiotics — a non-profit scientific organization that established the currently held definition of prebiotics — recommends an intake of 5 grams per day.

For the study, researchers used previously published scientific findings to analyze the prebiotic content of 8,690 foods contained in the Food and Nutrient Database for Dietary Studies, a resource many scientists use to study nutrition and health.

About 37% of the foods in the database were found to contain prebiotics. Dandelion greens, Jerusalem artichoke, garlic, leeks, and onions had the greatest amounts, ranging from about 100-240 milligrams of prebiotics per gram of food (mg/g). Other prebiotic rich foods included onion rings, creamed onions, cowpeas, asparagus, and Kellogg’s All-Bran cereal, each containing around 50-60 mg/g.

“The findings from our preliminary literature review suggest that onions and related foods contain multiple forms of prebiotics, leading to a larger total prebiotic content,” said Boyd. “Multiple forms of onions and related foods appear in a variety of dishes as both flavoring and main ingredients. These foods are commonly consumed by Americans and thus would be a feasible target for people to increase their prebiotic consumption.”

Based on the team’s findings, Boyd said a person would need to consume approximately half of a small (4-ounce) onion to get 5 grams of prebiotics.

Wheat-containing items rank lower on the list. Foods with little or no prebiotic content include dairy products, eggs, oils, and meats.

The researchers hope the study will provide a basis to help other scientists assess the health impacts of prebiotics and inform future dietary guidelines. They noted that more research is needed to understand how cooking impacts prebiotic content and to better assess foods that contain multiple ingredients.

Boyd will present this research at noon EDT on Saturday, July 22, during the Food Science and Nutrition Poster Session in the Hynes Convention Center Hall C (abstract; presentation details).

Please note that abstracts presented at NUTRITION 2023 were evaluated and selected by a committee of experts but have not generally undergone the same peer review process required for publication in a scientific journal. As such, the findings presented should be considered preliminary until a peer-reviewed publication is available.

About NUTRITION 2023

NUTRITION 2023 is the flagship meeting of the American Society for Nutrition and the premier educational event for nutritional professionals around the globe. NUTRITION brings together lab scientists, practicing clinicians, population health researchers, and community intervention investigators to identify solutions to today’s greatest nutrition challenges. Our audience also includes rising leaders in the field – undergraduate, graduate, and medical students. NUTRITION 2023 will be held July 22-25, 2023 in Boston. https://nutrition.org/N23 #Nutrition2023

About the American Society for Nutrition (ASN)

ASN is the preeminent professional organization for nutrition research scientists and clinicians around the world. Founded in 1928, the society brings together the top nutrition researchers, medical practitioners, policy makers and industry leaders to advance our knowledge and application of nutrition. ASN publishes four peer-reviewed journals and provides education and professional development opportunities to advance nutrition research, practice, and education. Since 2018, the American Society of Nutrition has presented NUTRITION, the leading global annual meeting for nutrition professionals. http://www.nutrition.org

Find more news briefs from NUTRITION 2023 at: https://www.eurekalert.org/newsroom/nutrition2023.

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American Society for Nutrition (ASN)

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July 22, 2023
New algorithm helped to find thousands of repeated elements in bacterial genome

Newswise — Scientists from The Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences (Research Center of Biotechnology RAS) elaborated mathematical algorithm that enabled to find dispersed repeated elements in genome with great accuracy. Authors tested this approach on genetic sequences of nine kinds of bacteria, and discovered early unknown repeats in all of them. Thus, for example, it turned out that almost 50% of genome of E. coli is presented by quite long repeats (400-600 pairs of nucleotides long). Such repeats represent a definite code, that is placed upon existing genes of bacteria over coding amino-acids. The found dispersed repeats can help to find new genetic targets, that are interesting from the point of view of biotechnology, for example, parts of DNA, impact on which will enable to increase productivity of bacterial strains. Results of the research are published in International Journal of Molecular Sciences.

In genomes of many eucaryotic (multicellular) organisms – from yeast to human – there are repeated sequences of nucleotides that are a kind of letters, that compose DNA. Each such repeat is several hundreds of nucleotides long and they are spread all over the whole genome. In sum they form a family that can have significant number of separate copies. The amount of such families, and also position and number of repeats in each family differ in various species and so they can tell about evolution and origin of different living organisms. There are many mathematical algorithms for searching of dispersed repeats (those ones that are more or less equally spread in a genome), such algorithms that even enable to find out “corrupted” copies, those repeats, where some mutations took place and the sequences of which are different from others. However, in the process of evolution such changes can be so numerous, that it becomes impossible to find in genome two insufficiently similar sequences. In this connection scientists search new approaches for searching of dispersed repeats, spread in genomes of various organisms. It is significant to note that such families of repeats were earlier found only in genomes of eukaryotes (multicellular) organisms, whereas they were unknown in organisms of bacteria.

Scientists from the Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences (Research Center of Biotechnology RAS) suggested a new method of searching of dispersed repeated sequences. Principle of its work can be compared with search of mathematic matrix, consisting of columns and lines, that describes the family of repeats in the best way. The suggested approach is optimal as far as accuracy of finding “dispersed” repeats in the whole genome is concerned, because it takes into account the ability of changing nucleotides and their insertions and deletions, in other words, mutations.

Researchers tested this algorithm on artificially generated sequences, that contained thousands of repeats each, a part of which contained mutations. A comparison with widely used in bioinformatics search systems showed that the suggested method enabled to find out repeats of one family with a greater number of mutations between them (up to the change of half of the nucleotides in a sequences) more precisely.

Then authors of the research applied algorithm for search of repeats in genome of nine kinds of bacteria: Escherichia coli, Bacillus subtilis, Azotobacter vinelandii, Clostridium tetani, Methylococcus capsulatus, Mycobacterium tuberculosis, Shigella sonnei, Treponema pallidum and Yersinia pestis. Analysis enabled scientists for the first time to find out three families of repeats, 400-600 pairs of nucleotides long, in Escherichia coli, which in total take almost 50% of the whole genome of bacterium. Earlier in this microorganism there were known similar elements only of less length – up to 300 pairs of nucleotides – and in smaller numbers. In genetic sequences in other bacteria, they managed to find 1-2 families of repeats of the same length (400-600 nucleotides). By this less of them were found in Treponema pallidum, that can be connected with small size of a genome of this microorganism.

“The found families of dispersed repeats are discovered in genes, and they represent a definite code placed on genes over triplet code, that provides coding of amino acid sequences by genes. By this it is not important on which DNA strand genes are situated. The obtained code can serve as a base for folding DNA in so called nucleoid, that in most degree defines expression of bacterial genes. It can be said that in bacterial DNA there is a code providing its folding into a nucleoid, and now we have obtained an ability to manage it. It opens great opportunities for creating new microorganisms, useful for people”, – tells about results of the research Eugine Korotkov, Doctor of Biological Sciences, head of the group of mathematical analysis of DNA sequences and proteins the Federal Research Centre “Fundamentals of Biotechnology” of the Russian Academy of Sciences (Research Center of Biotechnology RAS).

The suggested approach can be used for analysis not only of bacterial genomes, but also genetic sequences of multicellular organisms, for example, animals or plants. It can help to understand evolution of genomes and their separate elements better, and also in the case of bacteria to find targets for creating new antibiotics or increasing productivity of strains that are important for biotechnology.

Russian Foundation for Basic Research

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July 21, 2023
Biosurfactants: A Promising Environmentally-Friendly Approach to Combat Oil Spills

Newswise — Can biosurfactants increase microbiological oil degradation in North Sea seawater? An international research team from the universities of Stuttgart und Tübingen, together with the China West Normal University and the University of Georgia, have been exploring this question and the results have revealed the potential for a more effective and environmentally friendly oil spill response.

Oil leaks into the oceans are estimated at approximately 1500 million liters annually worldwide. This leads to globally significant environmental pollution, as oil contains hazardous compounds such as polycyclic aromatic hydrocarbons that can have toxic or mutagenic effects on organisms. Oil spills, particularly catastrophic ones resulting in the rapid release of large quantities of oil into the oceans, such as tanker accidents or incidents at oil drilling platforms like Deepwater Horizon in 2010, are especially devastating.

In such oil spill incidents, large quantities of chemical dispersants, ranging in the millions of liters depending on the amount of oil, are routinely applied to dissolve oil slicks, prevent oil from reaching coastlines, and enhance oil dispersion in the water. The hope is that microbial oil degradation will be enhanced as a result. This is because special microorganisms that are widespread in nature can feed on crude oil components and break them down into harmless substances. This special ability of microbes naturally cleans oil-contaminated areas.

“In a study from the USA published in 2015, we demonstrated that – contrary to expectation – chemical dispersants in deep-sea water from the Gulf of Mexico can slow down microbial oil degradation,” says Prof. Sara Kleindienst, who worked at the University of Tübingen until 2022 and now works at the University of Stuttgart. “Since then, the topic has been at the center of controversial discussions, and there is still no simple answer to how oil spills can be combated more effectively,” emphasizes Prof. Sara Kleindienst.

In the search for more environmentally friendly methods for dealing with oil spills, biosurfactants could offer a promising alternative to chemical dispersants. Biosurfactants are produced by microorganisms and can increase the bioavailability of oil components. This can thus enhance microbial oil degradation, which is crucial for purification.

Experiments with seawater from the North Sea
An international research team led by environmental microbiologist Professor Sara Kleindienst, with geomicrobiologist Professor Andreas Kappler (University of Tübingen) and biogeochemist Professor Samantha Joye (University of Georgia), compared the effects of biosurfactants and chemical dispersants. In the laboratory at the University of Tübingen, the researchers simulated oil spill conditions. For their experiment, they took over 100 liters of surface water from the North Sea close to the island of Helgoland. The seawater was treated with either the biosurfactant rhamnolipid or a dispersant (either Corexit 9500 or Slickgone NS), both in the presence and absence of oil. The research team used radioactive markers to track the degradation of the oil by the microorganisms in detail. “Our investigations using radioactively labeled hydrocarbons or a radioactively labeled amino acid showed that the highest rates of microbial hydrocarbon oxidation and protein synthesis occurred in the oil microcosms treated with rhamnolipid,” says Prof. Lu Lu, who previously worked at the University of Tübingen and now works at the China West Normal University.

The impact on the composition of microbial communities also differed significantly between the approaches using biosurfactants compared to chemical dispersants. “This result suggests that the use of biosurfactants may stimulate different microbial oil degraders, both in terms of growth and activity, which in turn can affect the cleanup process after oil spills,” says Prof. Lu Lu.

“Our findings suggest that biosurfactants have great potential for use in future oil spills in the North Sea or similar nutrient-rich ocean habitats,” adds Prof. Sara Kleindienst. “A visionary continuation of our work would be the development of products based on biosurfactants that offer both effective and environmentally friendly approaches to combating oil spills.”

University of Stuttgart

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July 21, 2023
Trevor Charles appointed to the Phytobiomes Alliance Board of Directors

Newswise — The International Alliance for Phytobiomes Research is pleased to announce the appointment of Trevor Charles as a new Board member of the organization.

Trevor Charles is Professor in the Department of Biology at University of Waterloo in Canada and Director of the Waterloo Centre for Microbial Research. A microbiologist with expertise in bacterial molecular genetics, Charles’ research focuses on plant-microbe interactions, functional metagenomics, and bacterial genome engineering for bio-products. Charles is Founder and CEO of the company Metagenom Bio Life Science Inc., a biotech company specializing in DNA sequencing solutions for microbiome research and analysis. He is also spearheading Healthy Hydroponics InnoTech Inc., a subsidiary of Metagenom Bio Life Science, a company providing pathogen monitoring services to hydroponic farms and growers to enhance prediction of crop diseases and food safety, as well as serving as CSO of the new inoculant company Earth Microbial Inc.

“I am truly honored to join the board of Phytobiomes Alliance, an organization that I have held in high esteem for its forward-looking role in the translation of Phytobiomes science with the ultimate aim of producing food in a more environmentally and economically sustainable manner,” said Trevor Charles. “I look forward to making contributions to the Phytobiomes Alliance and its varied stakeholders through membership on the Board. I am excited to collaborate with the other passionate Board members to drive positive change with the aim of creating a lasting impact on global food systems.”

“We are extremely pleased to have Trevor join the Board, he has been a continuous supporter of the Alliance internationally and a pioneer in expanding our understanding of microbes as part of controlled environment agriculture phytobiomes as well as designing microbial solutions specifically for these environments. The sustainable production of food, feed, and fiber in controlled environments will be important for fulfilling our needs for fresh and locally produced food in the future,” said Kellye Eversole, the Alliance Executive Director. “Trevor’s leadership and vision will be invaluable to shaping the Alliance strategy for the coming years.”

Charles has been a member of the Alliance Coordinating Committee since 2018. He was selected for the Board of Directors for his continuous efforts in supporting and promoting the overall advancement of phytobiomes science, and in particular for his leadership in controlled environment agriculture.

Launched in 2016, the non-profit International Phytobiomes Alliance facilitates and coordinates international efforts toward expanding phytobiomes research in order to accelerate the sustainable production of food, feed, and fiber for food security. The Board of Directors is in charge of setting the overall vision and mission of the Alliance and provides general oversight for the Alliance operations.

Charles will join the current Board members, Gwyn Beattie (Iowa State University), Natalie Breakfield (Newleaf Symbiotics), Kellye Eversole, Magalie Guilhabert (Ginkgo Bioworks), Jan Leach (Colorado State University), Emmanuelle Maguin (INRAE), Matthew Ryan (CABI) and Angela Sessitsch (Austrian Institute of Technology) for a three-year term.

About the Phytobiomes Alliance

The Phytobiomes Alliance is an international, nonprofit alliance of industry, academic, and governmental partners created in 2016. The goal of the Alliance is to understand, predict and control emergent phenotypes for sustainable production of food, feed and fiber on any given farm. The Phytobiomes Alliance is sponsored by Eversole Associates, INRAE, Valent BioSciences, Colorado State University, FarmBox Foods, IRD, Joyn Bio, the University of Nebraska-Lincoln, NewLeaf Symbiotics, Penn State College of Agricultural Sciences, Pivot Bio, Trace Genomics, the Waterloo Centre for Microbial Research, Aphea.Bio, and AIT Austrian Institute of Technology.

To learn more about the Alliance, visit phytobiomesalliance.org and follow @phytobiomes on Twitter.

International Phytobiomes Alliance

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July 12, 2023
Bacteria in kitchen not as harmful as feared

Newswise — Washington, D.C. – Bacteria found in 74 kitchens spread among 5 European countries were mostly harmless according to new research published in Applied and Environmental Microbiology, a journal of the American Society for Microbiology.

“We have previously found considerable variations in kitchen standards, food preparation practices, and cleaning regimes between France, Norway, Portugal, Romania, and Hungary,” said Birgitte Moen, Ph.D., Scientist—Department of Food Safety and Quality, Nofima—Norwegian Institute of Food, Fisheries, and Aquaculture Research, Ås, Norway.

In the study, the researchers sampled bacteria populations from sinks, cutting boards, counter tops, handles and cleaning utensils—sponges and cloths—used in kitchens.

Despite large numbers of species and considerable differences in bacterial diversity between samples, the researchers identified 8 bacterial genera commonly associated with environmental sources in most of the kitchens they sampled, which they characterized as “core microbiota.” These included Acinetobacter, Pseudomonas, Enhydrobacter, Enterobacteriaceae, Psychrobacter, Chryseobacterium, Bacillus and Staphylococcus.

In the report, the authors stressed that the core microbiota persisted despite considerable differences between kitchens in the study. Some kitchens lacked running water, some lacked an indoor sink and some lacked dishwashers. They also persisted despite differing food preparation methods, dietary habits and differences in hand and kitchen hygiene, both of which affect the probability of infection.

The study was motivated by the authors’ curiosity, said Moen. Bacteria in food, in the gut, in hospitals and in professional food production had been well researched, but little was known about the microbes that inhabit the domestic kitchen. With an already existing collaboration across countries, “we had a unique opportunity to dig into this,” Moen added.

The team knew that harmful bacteria enter kitchens via contaminated food, and that the type of these bacteria varied across countries. For example, Salmonella is not a problem in Norway, but it is the most commonly reported cause of foodborne illness in mainland Europe. Knowledge of the bacteria inhabiting the domestic kitchen could be used to help prevent human illness, and perhaps could even lead to more hygienic kitchen designs and better cleaning utensils, said Moen.

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American Society for Microbiology (ASM)

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July 11, 2023
Research Finds A Link Between The Gut & Preclinical Alzheimer’s

Dementia is currently the seventh leading cause of death 1 and one of the major causes of disability globally among older people, with Alzheimer’s disease (AD) making up 60 to 70% of dementia cases 1.

There is currently no cure for AD. But the earlier you can spot signs of it, the better—and new insights on the gut microbiome’s relationship to dementia may help with early detection.

A recent study published in Science Translational Medicine2 found that the gut microbiomes of symptomatic patients with Alzheimer’s differed from those of cognitively healthy control individuals who ate a similar diet.

For the cross-sectional study, researchers took gut microbiome samples from 164 individuals—49 of whom had biomarker evidence of early, preclinical Alzheimer’s. Those with preclinical AD were more likely to have some specific gut bacteria than those who did not have preclinical AD.

Knowing these unique microbiome features could eventually help improve the accuracy, sensitivity, and specificity of AD testing, the researchers note. However, they have not concluded a causal relationship quite yet. Though they found a correlation between these microbiome features and preclinical AD, they can’t say for sure whether these microbiome changes cause dementia or the other way around.

All of this to say: This area of dementia research is still in its early stages, so more studies are needed. Nevertheless, this finding could have a profound impact on preclinical dementia treatment. The method of pulling a stool sample is much more accessible and affordable than many of the traditional methods such as spinal taps and brain scans.

Hannah Frye

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July 5, 2023
Viome Vs. Ombre: An RN’s Comparison Of The Best Gut Tests

Gut health plays a significant role in our overall well-being and is increasingly being recognized for its impact on longevity. The gut, often referred to as the second brain, is populated by trillions of microorganisms known collectively as the gut microbiome. This complex ecosystem of bacteria, viruses, fungi, and other microorganisms is pivotal in several aspects of human health, including digestion, nutrient absorption, immune system function, and even mental health.

Emerging research suggests a healthy gut microbiome can contribute to healthy aging. A balanced gut microbiome aids optimal digestion and nutrient absorption, essential for maintaining overall health and warding off disease over the long term. Additionally, the gut microbiome plays a crucial role in immune system function. Around 70% of the immune system is located in the gut, and a healthy gut microbiome can support a robust immune response, reducing the risk of infection and illness.

Further, gut health is linked to inflammation, a key factor in many age-related diseases, such as cardiovascular disease, Alzheimer’s, and certain cancers. A healthy gut microbiome can help manage and reduce systemic inflammation, potentially reducing the risk of these diseases. Moreover, research has shown links between the gut microbiome and metabolic health. A balanced microbiome can aid in maintaining a healthy weight and managing blood sugar levels, factors also associated with longevity.

Prioritizing gut health may contribute to longevity by supporting optimal nutrient absorption, enhancing immune function, managing inflammation, and promoting metabolic health. As such, maintaining a balanced and diverse gut microbiome should be an important consideration for those seeking to live a long, healthy life.

Amanda Lundberg, RN

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June 21, 2023
Oral probiotic offers potential treatment for dry eye disease

Newswise — Houston, TX – In a study by a research group at Baylor College of Medicine, oral administration of a commercially available probiotic bacterial strain was found to improve dry eye disease in an animal model. The findings were presented at ASM Microbe 2023, the annual meeting of the American Society for Microbiology.

Dry eye, a common condition in which tears produced by the eye can’t keep the eye adequately lubricated, afflicts approximately 1 in 20 people in the United States. It can cause eye stinging and burning, inflammation, blurry vision and light sensitivity. Extreme cases can result in damage to the eye’s surface if left untreated. The most common treatments involve the application of eye drops, gels or ointment. This new, unconventional treatment involves bacteria in the intestinal tract.

Presenting author Laura Schaefer, Ph.D., of Baylor College of Medicine in Houston, Texas, said, “The ‘friendly’ bacteria that live in the human gastrointestinal tract have been linked to health and protection against disease in many parts of the body, including the gut, brain and lung. It’s therefore not surprising that the gut microbiome also has effects on our eyes.”

Previous work by this research group showed that mice given gut bacteria from human Sjögren syndrome patients with severe dry eye developed worse eye disease under dry conditions than mice that were given gut bacteria from healthy human patients. This suggests that the gut bacteria from healthy people help to protect the surface of the eye in dry conditions. One possible treatment avenue for dry eye would involve probiotic bacteria that have similar protective effects. The group investigated this by using an orally administered probiotic bacterial strain, Limosilactobacillus reuteri DSM17938, in a dry eye mouse model. DSM17938 is a human-derived, commercially available probiotic bacterial strain that has already demonstrated protective effects in the gut and immune system in humans and mice, but it has not been tested in the context of eye health.

Mice were first treated with antibiotics, which kills many of the “friendly” bacteria living in the gut. They were then exposed to very dry conditions and fed daily doses of either probiotic bacteria or a saline solution as a control. After 5 days, the eyes were examined for disease. The mice that were fed the probiotic bacteria had healthier and more intact corneal surfaces. In addition, these mice had more goblet cells in their eye tissue, which are specialized cells that produce mucin, an essential component in tears. Taken together these data suggest that the right oral probiotic could help treat and manage dry eye symptoms.

The authors in this study are Laura Schaefer, Robert Britton, Steven Pflugfelder and Cintia de Paiva. The research was performed in the laboratory of Dr. Cintia de Paiva in the Department of Ophthalmology at Baylor College of Medicine and supported with funds from the National Institutes of Health and the Research to Prevent Blindness Foundation.

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American Society for Microbiology (ASM)

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June 19, 2023
The Top 7 Health Benefits Of Almonds & Serving Size Tips

Though they are often referred to as a nut, almonds are technically a type of seed derived from almond trees. These trees are native to western Asia, but are now grown and cultivated around the globe. Compared to some other types of nuts, almonds come with a slightly steeper price tag, which is due to both their popularity and the labor-intensive harvesting processes required.

In terms of appearance, almonds are light brown and oval-shaped, with a smooth outer shell. They have a rich, nutty flavor that lends itself well to a wide range of recipes, adding an extra crunch to salads or bringing a tender texture to baked goods. They also make a healthy snack as is and can be enjoyed roasted, raw, or salted.

Rachael Ajmera, MS, RD

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June 19, 2023
Viome vs. Thorne: At-Home Gut Tests, Medically Reviewed

Viome is a pioneering health technology company that specializes in gut microbiome testing and analysis. The brand uses artificial intelligence and machine learning to interpret data about the microorganisms in your digestive tract and provide insights into your health and well-being.

Users receive a kit, wherein they provide stool, blood, and saliva samples. These are then sent back to Viome’s lab for review. Leveraging advanced metatranscriptomic sequencing technology, Viome identifies all microbes (such as bacteria, viruses, yeast, fungi, and mold, in addition to human, bacterial, and microbial RNA) to give a deep dive into your microbiome.

After this sequencing and analysis process, users receive a detailed report on their microbiome composition, functionality, and how it may affect various aspects of their health. This report provides insights into the individual’s metabolic health, inflammation, digestive efficiency, and more, providing a holistic view of gut health.

Based on your results, Viome offers personalized nutrition recommendations to support optimal health. The purpose is to empower users to make informed decisions about their diet, lifestyle, and general health, thereby creating a customized path toward improved wellness.

Amanda Lundberg, RN

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June 16, 2023
A New Strategy to Break Through Bacterial Barriers in Chronic Treatment-Resistant Wounds

Newswise — CHAPEL HILL, N.C. – Chronic wounds are open sores or injured tissue that fail to heal properly. These types of wounds are notoriously challenging to treat because of bacterial infections like Staphylococcus aureus, or S. aureus. Additionally, bacterial infections that are highly resistant to antibiotics, such as methicillin-resistant S. aureus (MRSA), are one of the main causes of life-threatening infections in hospital patients.

To defend itself from our immune system and other threats, S. aureus can band together, creating a slick, slimy forcefield – or biofilm – around itself. The biofilm barrier is so thick that neither immune cells nor antibiotics can penetrate through and neutralize the harmful bacteria.

Researchers at the UNC School of Medicine and the UNC-NC State Joint Department of Biomedical Engineering have developed a new method that combines palmitoleic acid, gentamicin, and non-invasive ultrasound to help improve drug delivery in chronic wounds that have been infected with S. aureus.

Using their new strategy, researchers were able to reduce the challenging MRSA infection in the wounds of diabetic mice by 94%. They were able to completely sterilize the wounds in several of the mice, and the rest had significantly reduced bacterial burden. Their results were published in Cell Chemical Biology.

“When bacteria are not completely cleared from chronic wounds, it puts the patient at high risk for the infection recurring or of developing a secondary infection,” said senior author Sarah Rowe-Conlon, PhD, a research associate professor in the Department of Microbiology and Immunology. “This therapeutic strategy has the potential to improve outcomes and reduce relapse of chronic wound infections in patients. We are excited about the potential of translating this to the clinic, and that’s what we’re exploring right now.”

Biofilms act as a physical barrier to many classes of antibiotics. Virginie Papadopoulou, PhD, a research assistant professor in the UNC-NCSU Joint Department of Biomedical Engineering, was curious to know if non-invasive cavitation-enhanced ultrasound could create enough agitation to form open spaces in the biofilm to facilitate drug-delivery.

Liquid droplets which can be activated by ultrasound, called phase change contrast agent (PCCA), are applied topically to the wound. An ultrasound transducer is focused on the wound and turned on, causing the liquid inside the droplets to expand and turn into microscopic gas-filled microbubbles, when then move rapidly.

The oscillation of these microbubbles agitates the biofilm, both mechanically disrupting it as well as increasing fluid flow. Ultimately, the combination of the biofilm disruption and the increased permeation of the drugs through the biofilm allowed the drugs to come in and kill the bacterial biofilm with very high efficiency.

“Microbubbles and phase change contrast agents act as local amplifiers of ultrasound energy, allowing us to precisely target wounds and areas of the body to achieve therapeutic outcomes not possible with standard ultrasound,” said Dayton, the William R. Kenan Jr. Distinguished Professor and Department Chair of the UNC-NCSU Joint Department of Biomedical Engineering. “We hope to be able to use similar technologies to locally delivery chemotherapeutics to stubborn tumors or drive new genetic material into damaged cells as well.”

When the bacterial cells are trapped inside the biofilm, they are left with little access to nutrients and oxygen. To conserve their resources and energy, they transition into a dormant or sleepy state. The bacteria, which are known as persister cells in this state, are extremely resistant to antibiotics.

Researchers chose gentamicin, a topical antibiotic typically ineffective against S. aureus due to widespread antibiotic resistance and poor activity against persister cells. The researchers also introduced a novel antibiotic adjuvant, palmitoleic acid, to their models.

Palmitoleic acid, an unsaturated fatty acid, is a natural product of the human body that has strong antibacterial properties. The fatty acid embeds itself into the membrane of bacterial cells, and the authors discovered that it facilitates the antibiotic’s successful entry into S. aureus cells and is able to kill persister cells and reverse antibiotic resistance.

Overall, the team is enthusiastic about the new topical, non-invasive approach because it may give scientists and doctors more tools to combat antibiotic resistance and to lessen the serious adverse effects of taking oral antibiotics.

“Systemic antibiotics, such as oral or IV, work very well, but there’s often a large risk associated with them such as toxicity, wiping out gut microflora and C. difficile infection,” said Rowe-Conlon. “Using this system, we are able to make topical drugs work and they can be applied to the site of infection at very high concentrations, without the risks associated with systemic delivery.”

About UNC School of Medicine

The UNC School of Medicine (SOM) is the state’s largest medical school, graduating more than 180 new physicians each year. It is consistently ranked among the top medical schools in the US, including 5^th overall for primary care by US News & World Report, and 6^th for research among public universities. More than half of the school’s 1,700 faculty members served as principal investigators on active research awards in 2021. Two UNC SOM faculty members have earned Nobel Prize awards.

About the Joint Department of Biomedical Engineering

The Joint Department is ranked in the top 10 biomedical engineering programs in the US by the Blue Ridge Institute for Medical Research, top 20 biomedical engineering programs worldwide by the Shanghai Academic Ranking of World Universities, and is a top 5 institution for total bachelor’s degrees awarded in biomedical engineering (ASEE).

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University of North Carolina School of Medicine

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May 22, 2023
Mycobiome Communities 101: Their Effect on Health & Disease

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 obesity 3).

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.

Mahmoud Ghannoum, Ph.D.

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May 15, 2023
New Method Uses Engineered Bacteria and AI to Sense and Record Environmental Signals

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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May 9, 2023
First microbiome-targeting drug using CRISPR created by scientists
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.
Technical University of Denmark (DTU)

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May 9, 2023