Deoxycholic acid formation in gnotobiotic mice associated with human intestinal bacteria

Abstract

In humans and animals, intestinal flora is indispensable for bile acid transformation. The goal of our study was to establish gnotobiotic mice with intestinal bacteria of human origin in order to examine the role of intestinal bacteria in the transformation of bile acids in vivo using the technique of gnotobiology. Eight strains of bile acid-deconjugating bacteria were isolated from ex-germ-free mice inoculated with a human fecal dilution of 10(-6), and five strains of 7alpha-dehydroxylating bacteria were isolated from the intestine of limited human flora mice inoculated only with clostridia. The results of biochemical tests and 16S rDNA sequence analysis showed that seven out of eight bile acid-deconjugating strains belong to a bacteroides cluster (Bacteroides vulgatus, B. distasonis, and B. uniformis), and one strain had high similarity with Bilophila wadsworthia. All five strains that converted cholic acid to deoxycholic acid had greatest similarity with Clostridium hylemonae. A combination of 10 isolated strains converted taurocholic acid into deoxycholic acid both in vitro and in the mouse intestine. These results indicate that the predominant bacteria, mainly Bacteroides, in human feces comprise one of the main bacterial groups for the deconjugation of bile acids, and clostridia may play an important role in 7aplha-dehydroxylation of free-form primary bile acids in the intestine although these strains are not predominant. The gnotobiotic mouse with bacteria of human origin could be a useful model in studies of bile acid metabolism by human intestinal bacteria in vivo.

Consequences of bile salt biotransformations by intestinal bacteria

“…Germ-free animals have been shown to lack secondary bile acids. 56,57 Bacteria capable of converting primary to secondary bile acids have been isolated from humans. [58][59][60] The rodent isolate required unidentified Bacteroides spp.…”

Gut microbiome development along the colorectal adenoma–carcinoma sequence

“…6, Supplementary Figs 8 and 9). Carcinoma-enriched bacteria that produce short chain fatty acids, the major energy source for colonocytes, through amino acid fermentation, and/or bacteria that metabolize bile acids 24,25 , for example, B. massiliensis, B. dorei, B. vulgates, Parabacteroides merdae, A. finegoldii and B. wadsworthia, showed a positive correlation with consumption of red meat and/or a negative correlation with consumption of fruits and vegetables (Fig. 6), suggesting a common pathway in colorectal tumourigenesis.…”

Distinct signatures of host–microbial meta-metabolome and gut microbiome in two C57BL/6 strains under high-fat diet

“…As one example, DCA is one of the major secondary BAs derived through dehydroxylation of bacteria in the gut. Narushima et al (2006) indicate that Bacteroides is the main bacterial genus that is responsible for the dehydroxylation of CA to DCA. In our study, elevated BAs and simultaneously higher abundances of B. acidifaciens could be observed in the C57J strain, indicating that co-occurrence of elevated BAs and B. acidifaciens could provide a protection against HFD-induced obesity in C57J mice.…”