Journal
GUT MICROBES
Volume 10, Issue 4, Pages 481-503Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/19490976.2018.1549420
Keywords
Bile salts; 7 alpha-dehydroxylation pathway; clostridium; commensal bacteria; intestinal colonization; gut ecology; lithocholic acid (LCA); deoxycholic acid (DCA); 12-oxo bile acids; stable isotopes
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Funding
- Swiss National Science Foundation [CRSII3_147603, CRSII5_180317]
- Swiss National Science Foundation (SNF) [CRSII5_180317, CRSII3_147603] Funding Source: Swiss National Science Foundation (SNF)
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The human gut hosts trillions of microorganisms that exert a profound influence on human biology. Gut bacteria communicate with their host by secreting small molecules that can signal to distant organs in the body. Bile acids are one class of these signaling molecules, synthesized by the host and chemically transformed by the gut microbiota. Among bile acid metabolizers, bile acid 7-dehydroxylating bacteria are commensals of particular importance as they carry out the 7-dehydroxylation of liver-derived primary bile acids to 7-dehydroxylated bile acids. The latter represents a major fraction of the secondary bile acid pool. The microbiology of this group of gut microorganisms is understudied and warrants more attention. Here, we detail the bile acid transformations carried out by the 7-dehydroxylating bacterium Clostridium scindens in vitro and in vivo. In vitro, C. scindens exhibits not only 7 alpha-dehydroxylating capabilities but also, the ability to oxidize other hydroxyl groups and reduce ketone groups in primary and secondary bile acids. This study revealed 12-oxolithocholic acid as a major transient product in the 7 alpha-dehydroxylation of cholic add. Furthermore, the in vivo study included complementing a gnotobiotic mouse line (devoid of the ability to 7-dehydroxylate bile acids) with C. scindens and investigating its colonization dynamics and bile acid transformations. Using NanoSIMS (Nanoscale Secondary Ion Mass Spectrometry), we demonstrate that the large intestine constitutes a niche for C. scindens, where it efficiently 7-dehydroxylates cholic acid to deoxycholic acid. Overall, this work reveals a novel transient species during 7-dehydroxylation as well as provides direct evidence for the colonization and growth of 7-dehydroxylating bacteria in the large intestine.
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