Comparative Genomic and Physiological Analysis against <i>Clostridium scindens</i> Reveals <i>Eubacterium</i> sp. c-25 as an Atypical Deoxycholic Acid Producer of the Human Gut Microbiota

The human gut houses bile acid 7α-dehydroxylating bacteria that produce secondary bile acids such as deoxycholic acid (DCA) from host-derived bile acids through enzymes encoded by the <i>bai</i> operon. While recent metagenomic studies suggest that these bacteria are highly diverse and a...

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Autores principales: Isaiah Song, Yasuhiro Gotoh, Yoshitoshi Ogura, Tetsuya Hayashi, Satoru Fukiya, Atsushi Yokota
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/d79fed6750774323881d9ddc25a6f2d1
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Sumario:The human gut houses bile acid 7α-dehydroxylating bacteria that produce secondary bile acids such as deoxycholic acid (DCA) from host-derived bile acids through enzymes encoded by the <i>bai</i> operon. While recent metagenomic studies suggest that these bacteria are highly diverse and abundant, very few DCA producers have been identified. Here, we investigated the physiology and determined the complete genome sequence of <i>Eubacterium</i> sp. c-25, a DCA producer that was isolated from human feces in the 1980s. Culture experiments showed a preference for neutral to slightly alkaline pH in both growth and DCA production. Genomic analyses revealed that c-25 is phylogenetically distinct from known DCA producers and possesses a multi-cluster arrangement of predicted bile-acid inducible (<i>bai</i>) genes that is considerably different from the typical <i>bai</i> operon structure. This arrangement is also found in other intestinal bacterial species, possibly indicative of unconfirmed 7α-dehydroxylation capabilities. Functionality of the predicted <i>bai</i> genes was supported by the induced expression of <i>baiB</i>, <i>baiCD</i>, and <i>baiH</i> in the presence of cholic acid substrate. Taken together, <i>Eubacterium</i> sp. c-25 is an atypical DCA producer with a novel <i>bai</i> gene cluster structure that may represent an unexplored genotype of DCA producers in the human gut.