COVID-19 Infection Can Be Inhibited by Elements of the Human Microbiome

AHA Publisher — Tue, 07 Dec 2021 08:00:39 +0000

American Society for Microbiology (ASM) via Newswise – Washington, D.C. – December 1, 2021– Researchers have identified metabolites, intermediate or end products of metabolism, in the human microbiome that inhibit COVID-19 infection in cell-based models of the virus. The finding, reported this week in the journal mSphere, an open-access journal of the American Society for Microbiology, is yet another example of the wealth of information that can be gained by studying the human microbiome, the collection of microbes, bacteria, fungi and viruses that live on and inside the human body. The finding may also help in the development of new therapeutics that can battle COVID-19 infections. “We have found that bacteria that grow on and in you make specific molecules that can inhibit, at least in a laboratory setting, the cell based viral infection of SARS-CoV-2, and the molecules appear to do that by a number of different mechanisms,” said study principal investigator Sean Brady, Ph.D., professor and head of the Laboratory of Genetically Encoded Small Molecules, at the Rockefeller University, New York City. Brady said the COVID-19 pandemic has highlighted the need to identify additional antiviral small molecules to complement existing therapies. While increasing evidence suggests that metabolites produced by the human microbiome have diverse biological activities affecting the human host, there is comparatively little information on the metabolites’ antiviral properties. In the new study, Brady and colleagues used a cell-based SARS-CoV-2 infection assay to screen metabolites from a sample of bacteria from the human microbiome. They identified 3 bacterial metabolites capable of inhibiting SARS-CoV-2 infection: an adenosine analogue, tryptamine and a disubstituted pyrazine. The identified molecules display structural similarities to synthetic drugs that have been explored for the treatment of COVID-19. “It was intriguing that of all the chemistries available, the metabolites we uncovered from the microbiome all bore similarities to clinically-relevant antivirals,” said Frank Piscotta, Ph.D., lead author on the study and a post-doc in the Laboratory of Genetically Encoded Small Molecules. The researchers say these molecules could serve as starting points for the development of new antivirals. In addition, researchers could deliver the antiviral-producing bacteria as a therapeutic intervention. The researchers say they want to study the mechanisms by which the metabolites function and whether the bacteria producing these molecules have any effect on viral infection upon colonization of an animal. As more data becomes available, they also plan to examine whether the presence or absence of these antiviral-producing bacteria in humans can be linked to severity of viral infection. “Our discovery of structurally diverse metabolites with anti-SARS-CoV-2 activity from screening a small fraction of the bacteria reported to be associated with the human microbiome suggests that continued exploration of phylogenetically diverse human-associated bacteria is likely to uncover additional small molecules that inhibit SARS-CoV-2 as well as other viral infections,” said Brady. Brady says this is one of the first studies to show that molecules produced by the human microbiome can inhibit viral infections, particularly of coronaviruses like SARS-CoV-2. To read the original article click here.

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Researchers Link “Genetic Signatures” of Bacteria in the Human Gut to Multiple Diseases

AHA Publisher — Thu, 20 May 2021 07:00:24 +0000

Harvard Medical School via News-Medical – We are truly never alone, not even within our own bodies. Human beings play host to trillions of bacteria, fungi, viruses, and other microorganisms that make up the human microbiome. In recent years, the mix of these resident bacteria, and the presence of specific bacterial species, has been linked to conditions ranging from obesity to multiple sclerosis. Now, going a step farther, researchers at Harvard Medical School and Joslin Diabetes Center have gone beyond microbial species. Analyzing the genetic makeup of bacteria in the human gut, the team has successfully linked groups of bacterial genes, or “genetic signatures,” to multiple diseases. The work brings scientists closer to developing tests that could predict disease risk or identify disease presence based on a sampling of the genetic makeup of a person’s microbiome. The findings, to be published May 18 in Nature Communications, link sets of bacterial genes to the presence of coronary artery disease, cirrhosis of the liver, inflammatory bowel disease, colon cancer, and type 2 diabetes. The analysis indicates that three of these conditions–coronary artery disease, inflammatory bowel disease, and liver cirrhosis–share many of the same bacterial genes. In other words, people whose guts harbor these bacterial genes seem more likely to have one or more of these three conditions. The work represents a significant advance in the current understanding of the relationship between microbes residing in the human gut and specific diseases, the team said. If confirmed through further research, the results could inform the design of tools that could gauge a person’s risk for a range of conditions based on analysis of a single fecal sample, they added. “This opens a window for the development of tests using cross-disease, gene-based indicators of patient health. We’ve identified genetic markers that we think could eventually lead to tests, or just one test, to identify associations with a number of medical conditions.” (Braden Tierney, Study First Author and Graduate Student, Biological and Biomedical Sciences Program, Harvard Medical School) The researchers caution that their study was not designed to elucidate exactly how and why these microbial genes may be linked to different diseases. Thus far, they said, it remains unclear whether these bacteria are involved in disease development or are mere bystanders in this process. The goal of the study was to determine whether groups of genes could reliably indicate the presence of different diseases. These newly identified microbial genetic signatures, however, could be studied further to determine what role, if any, the organisms play in disease development. “Our study underscores the value of data science to tease out complex interplay between microbes and humans,” said study senior author Chirag Patel, associate professor of biomedical informatics in the Blavatnik Institute at HMS. The researchers started out by collecting microbiome data from 13 groups of patients totaling more than 2,500 samples. Next, they analyzed the data to pinpoint linkages between seven diseases and millions of microbial species, microbial metabolic pathways, and microbial genes. By trying out a variety of modeling approaches–computing a total of 67 million different statistical models–they were able to observe what microbiome features consistently emerged as the strongest disease-associated candidates. Of all the various microbial characteristics–species, pathways, and genes–microbial genes had the greatest predictive power. In other words, the researchers said, groups of bacterial genes, or genetic signatures, rather than merely the presence of certain bacterial families, were linked most closely to the presence of a given condition. Some of the main observations included: Clusters of bacterial genes, or genetic signatures, rather than individual bacterial genes, appear implicated in various types of human disease. Coronary artery disease, inflammatory bowel disease, and liver cirrhosis have similar gut microbiome genetic signatures. Type 2 diabetes, by contrast, has a microbiome signature unlike any other phenotype tested. The analysis did not find a consistent link between the presence of the bacterial species Solobacterium moorei and colon cancer–an association previously reported in numerous studies. However, the researchers did identify particular genes from a S. moorei subspecies associated with colorectal cancer. This finding indicates that gene-level analysis can yield biomarkers of disease with greater precision and more specificity compared with current approaches. Patel said this result underscores the notion that it is not merely the presence of a given bacterial family that may portend risk, but rather the strains and gene signatures of the microbes that matter. The ability to identify interconnections with such precision will be critical for designing tests that can measure risk reliably, he added. Thus, in this specific example, a test intended to measure colon-cancer risk by merely detecting the presence of S. moorei in the gut may not be as reliable as a more refined test that measures bacterial genes to detect the presence of specific strains of S. moorei that are associated with colon cancer. Two conditions–ear inflammation and benign soft-tissue tumors called adenomas–showed weak associations with the gut microbiome, suggesting that microorganisms residing in the human gut are not likely to play a role in the development of these conditions, nor are they likely to be reliable indicators that these conditions are present. In a previous study, the HMS team used massive amounts of publicly available DNA-sequencing data from human oral and gut microbiomes to estimate the size of the universe of microbial genes in the human body. The analysis revealed that there may be more genes in the collective human microbiome than stars in the observable universe. Given the sheer number of microbial genes that reside within the human body, the new findings represent a major step forward in understanding the complexity of the interplay between human diseases and the human microbiome, the researchers said. “The ultimate goal of computational science is to generate hypotheses from a huge swath of data,” said Tierney. “Our work shows that this can be done and opens up so many new avenues for research and inquiry that we are only limited by the time, people, and resources needed to run those tests.” To read the original article click here.

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COVID-19 Infection Can Be Inhibited by Elements of the Human Microbiome

Researchers Link “Genetic Signatures” of Bacteria in the Human Gut to Multiple Diseases