What is already known on this topic
The gut microbiota can influence human health through the production of small molecules called metabolites. Tools that measure metabolite levels can help to investigate how gut microbes influence human physiology, but it’s still unclear which microbes or enzymes are involved in the production of specific metabolites.
What this research adds
Researchers developed a new way to study microbial metabolism: the approach detects microbial metabolites in diverse biological samples and traces them back to the metabolic profiles of bacteria grown in a lab dish. First, the team created a reference database of more than 800 microbial metabolites. Then, using this database, the researchers measured the metabolic profiles of 178 types of gut microbes and discovered a previously undescribed mechanism through which Bacteroidetes use the amino acids glutamine and asparagine.
The new approach could help characterize microorganisms and their interactions with the human body.
The gut microbiota can influence human health through the production of small molecules called metabolites, but it’s still unclear which microbes or enzymes are involved in the production of specific metabolites. Now, researchers have developed a new approach to study microbial metabolism that works by detecting microbial metabolites in diverse biological samples and trace them back to the metabolic profiles of bacteria grown in a lab dish.
The approach, detailed in Nature, could help characterize microorganisms and their interactions with the human body. “Adding previously undescribed microbially derived metabolites, along with new strains such as those isolated from diverse human populations, will uncover new mediators of the interactions between the host and microbiota as well as molecular targets for therapeutic interventions,” the researchers say.
Tools that measure metabolite levels can help to investigate how gut microbes influence human physiology. However, technologies that detect the products of anaerobic metabolism in the gut are still limited. So, researchers led by Stanford University School of Medicine’s Dylan Dodd, Michael Fischbach, and Justin Sonnenburg set out to develop a tool to accelerate the identification of microbial metabolites in different types of samples.
First, the researchers used mass spectrometry, a technique that identifies molecules by their mass and charge, to create a reference database of 833 microbial metabolites. All these metabolites are detectable in biological samples such as feces and blood, the team found.
Next, the researchers developed a pipeline that helps to identify the compounds and carry out statistical analyses. The team used the reference database to measure the metabolic profiles of 178 microbial strains grown from different tissues of mice whose guts were colonized by either individual strains or communities of five to six bacterial species.
“We construct an atlas of gut-microbiota-dependent metabolic activities in vitro and in vivo, enabling functional studies of gut microbial communities,” the researchers say.
Identifying microbial metabolites
Using their microbial atlas, the team identified the bacteria that produce specific metabolites. For example, Enterococcus faecalis and Enterococcus faecium appear to produce high levels of tyramine — a molecule known to modulate host neurological functions, whereas Clostridium cadaveris uses high levels of vitamin B5, which is associated with inflammatory bowel diseases.
Next, the researchers paired the metabolomic analyses with analyses of bacterial genomes to identify the genes responsible for yet-unexplained metabolic capacities. They discovered a previously undescribed mechanism through which Bacteroides consume the amino acids glutamine and asparagine. These two amino acids can be used as the only sources of nitrogen by most Bacteroides, the researchers found. “Previous studies showing that Bacteroides could not use free amino acids as the sole nitrogen source did not test asparagine and glutamine,” the authors note.
The new tool, which includes a large metabolomics data set of thousands of samples, could be useful to the research community. “Our existing strain-specific genome-by-metabolic profile data provides a rich resource for the comparative discovery of genes and pathways that underlie bacterial phenotypic variation,” the researchers say. A better understanding of microbial metabolism could help to develop new drugs that target the gut microbiota, they add.