Journal
MSYSTEMS
Volume 6, Issue 4, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/mSystems.00805-21
Keywords
bile acids; gut bacteria; microbially conjugated bile acids; conjugation; mass spectrometry; microbiome
Categories
Funding
- National Institutes of Health (NIH) [DK108259]
- Transatlantic Networks of Excellence Award from the Leducq Foundation
- National Science Foundation (NSF) [1715710]
- National Institute of General Medical Sciences of the National Institutes of Health [T32GM008349, T32GM135066]
- University of Wisconsin-Madison SciMed Graduate Research Scholars Fellowship
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [1715710] Funding Source: National Science Foundation
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Gut bacteria play a critical role in modifying primary bile acids synthesized by the host, leading to the production of secondary bile acids that can regulate metabolic processes and influence gut microbiota composition. Through screening 72 bacterial isolates, this study identified 43 isolates capable of modifying unconjugated bile acids, expanding the known diversity of bacteria involved in bile acid transformations. The discovery of novel microbial conjugated bile acids and previously undescribed species highlights the importance of understanding the interactions between the microbiome, bile acid pool composition, and human health.
Gut bacteria influence human physiology by chemically modifying hostsynthesized primary bile acids. These modified bile acids, known as secondary bile acids, can act as signaling molecules that modulate host lipid, glucose, and energy metabolism and affect gut microbiota composition via selective antimicrobial properties. However, knowledge regarding the bile acid-transforming capabilities of individual gut microbes remains limited. To help address this knowledge gap, we screened 72 bacterial isolates, spanning seven major phyla commonly found in the human gut, for their ability to chemically modify unconjugated bile acids. We found that 43 isolates, representing 41 species, were capable of in vitro modification of one or more of the three most abundant unconjugated bile acids in humans: cholic acid, chenodeoxycholic acid, and deoxycholic acid. Of these, 32 species have not been previously described as bile acid transformers. The most prevalent bile acid transformations detected were oxidation of 3a-, 7a-, or 12a- hydroxyl groups on the steroid core, a reaction catalyzed by hydroxysteroid dehydrogenases. In addition, we found 7a- dehydroxylation activity to be distributed across various bacterial genera, and we observed several other complex bile acid transformations. Finally, our screen revealed widespread bacterial conjugation of primary and secondary bile acids to glycine, a process that was thought to only occur in the liver, and to 15 other amino acids, resulting in the discovery of 44 novel microbially conjugated bile acids. IMPORTANCE Our current knowledge regarding microbial bile acid transformations comes primarily from biochemical studies on a relatively small number of species or from bioinformatic predictions that rely on homology to known bile acid-transforming enzyme sequences. Therefore, much remains to be learned regarding the variety of bile acid transformations and their representation across gut microbial species. By carrying out a systematic investigation of bacterial species commonly found in the human intestinal tract, this study helps better define the gut bacteria that impact composition of the bile acid pool, which has implications in the context of metabolic disorders and cancers of the digestive tract. Our results greatly expand upon the list of bacterial species known to perform different types of bile acid transformations. This knowledge will be vital for assessing the causal connections between the microbiome, bile acid pool composition, and human health.
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