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Deoxycholic acid formation in gnotobiotic mice associated with human intestinal bacteria

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Lipids

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 7α-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 7α-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.

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Abbreviations

EG:

Eggerth-Gagnon

EGF:

Eggerth-Gagnon Fildes

GB:

gnotobiotic

GF:

germ-free

MPYG:

modified peptone-yeast-glucose

TS:

tripticase soy

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Authors and Affiliations

  1. Laboratory of Veterinary Public Health, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo 1-1-1 Yayoi, Bunkyo-ku, 113-8657, Tokyo, Japan

    Seiko Narushima, Kikuji Itoh, Yukiko Miyamoto, Sang-Hee Park & Keiko Nagata

  2. Shionogi Research Laboratories, Toyonaka, 561-0825, Osaka, Japan

    Kazuo Kuruma

  3. Department of Pathphysiological and Therapeutic Science, School of Medicine, Tottori University, 86 Nishi-cho, 683-8503, Yonago, Japan

    Kiyohisa Uchida

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  1. Seiko Narushima
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  2. Kikuji Itoh
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  3. Yukiko Miyamoto
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  4. Sang-Hee Park
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  5. Keiko Nagata
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  6. Kazuo Kuruma
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  7. Kiyohisa Uchida
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Correspondence to Kikuji Itoh.

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Narushima, S., Itoh, K., Miyamoto, Y. et al. Deoxycholic acid formation in gnotobiotic mice associated with human intestinal bacteria. Lipids 41, 835–843 (2006). https://doi.org/10.1007/s11745-006-5038-1

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