The gut bacterium <i>Extibacter muris</i> produces secondary bile acids and influences liver physiology in gnotobiotic mice

Streidl, Theresa; Karkossa, Isabel; Muñoz, Rafael R. Segura; Eberl, Claudia; Zaufel, Alex; Plagge, Johannes; Schmaltz, Robert; Schubert, Kristin; Basic, Marijana; Schneider, Kai Markus; Afify, Mohamed; Trautwein, Christian; Tolba, René; Stecher, Bärbel; Doden, Heidi L.; Ridlon, Jason M.; Ecker, Josef; Moustafa, Tarek; Bergen, Martin von; Ramer‐Tait, Amanda E.; Clavel, Thomas

doi:10.1080/19490976.2020.1854008

Cited by 192 publications

(67 citation statements)

References 95 publications

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“…is strong evidence for the existence of alternative bai genotypes in intestinal DCA producers. Large-scale metagenomic analyses suggest that bai genes are much more common in intestinal microbial communities than previously believed [17,72], calling into question the actual numbers and diversity of DCA producers beyond the few identified thus far [15,19].…”

Section: Discussionmentioning

confidence: 94%

“…The core genes (baiA2-I) each encode a necessary enzyme in the multi-step 7α-dehydroxylation pathway and form a single operon [14] (Figure 1). While substantial amounts of DCA are produced solely by microbial biotransformation [3], the currently known DCA producers consist of a very small number of species belonging to the genus Clostridium and other closely related genera [2,15]. Their actual population numbers and diversity are unknown.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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 bai 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 Eubacterium 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 (bai) genes that is considerably different from the typical bai operon structure. This arrangement is also found in other intestinal bacterial species, possibly indicative of unconfirmed 7α-dehydroxylation capabilities. Functionality of the predicted bai genes was supported by the induced expression of baiB, baiCD, and baiH in the presence of cholic acid substrate. Taken together, Eubacterium sp. c-25 is an atypical DCA producer with a novel bai gene cluster structure that may represent an unexplored genotype of DCA producers in the human gut.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…A widely used example, the OligoMM12, is a gnotobiotic consortium of 12 cultivable mouse-derived strains representing the major five bacterial phyla in the murine gut (Brugiroux et al, 2016). It is reproducible between facilities (Eberl et al, 2020) and extensive data now exists on the metabolism of individual species and their interactions with each other and the host (Streidl et al, 2021;Weiss et al, 2021;Wotzka et al, 2019;Yilmaz et al, 2021). However, working with these mice involves hygiene conditions similar to those required to work with germfree mice, which poses a technical challenge for the long-term analysis of mouse metabolism.…”

Section: Introductionmentioning

confidence: 99%

Metabolic reconstitution by a gnotobiotic microbiota varies over the circadian cycle

Hoces

Lan

Sun

et al. 2021

Preprint

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Microbiota composition correlates with host metabolic health in both humans and mice. Here we investigated the extent to which a gnotobiotic microbiota can mimic the influence of a complete microbiota on mouse metabolism using an isolator-housed TSE-PhenoMaster® system. We found that energy expenditure was equivalent between germ-free (GF) and specific-opportunistic-pathogen free line (SPF) mice, and we extend this observation to the OligoMM12 microbiota (12 species across 5 phyla that are naturally abundant in a murine gut microbiota). Moreover, microbiota-released calories were well compensated by food intake in all groups. However, each group of mice have a distinctive circadian metabolic profile. OligoMM12 clustered with GF during the light phase, but with SPF during the dark phase for both RER and metabolome. Therefore, interactions between the host and a reductionist microbiota are non-uniform over the circadian cycle, revealing a promising tool to identify key microbiota species/functions that modify host metabolism.

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“…Projects such as the establishment of the "mouse intestinal bacterial collection" (miBC) will serve as an essential resource, offering access to defined bacteria and microbiological communities [236]. This includes the "Oligo Mouse Microbiota12" (OMM 12 ), representing 12 members of the major bacterial phyla in the murine gut providing colonization resistance against Salmonella typhimurium [232,234] This consortium is currently being modified to enhance complexity or to select for certain community characteristics and might represent an ideal modular system for the future [237][238][239][240].…”

Section: Microbiome On Demand-gnotobiologymentioning

confidence: 99%

Health Monitoring of Laboratory Rodent Colonies—Talking about (R)evolution

Buchheister

Bleich

2021

Animals

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The health monitoring of laboratory rodents is essential for ensuring animal health and standardization in biomedical research. Progress in housing, gnotobiotic derivation, and hygienic monitoring programs led to enormous improvement of the microbiological quality of laboratory animals. While traditional health monitoring and pathogen detection methods still serve as powerful tools for the diagnostics of common animal diseases, molecular methods develop rapidly and not only improve test sensitivities but also allow high throughput analyses of various sample types. Concurrently, to the progress in pathogen detection and elimination, the research community becomes increasingly aware of the striking influence of microbiome compositions in laboratory animals, affecting disease phenotypes and the scientific value of research data. As repeated re-derivation cycles and strict barrier husbandry of laboratory rodents resulted in a limited diversity of the animals’ gut microbiome, future monitoring approaches will have to reform—aiming at enhancing the validity of animal experiments. This review will recapitulate common health monitoring concepts and, moreover, outline strategies and measures on coping with microbiome variation in order to increase reproducibility, replicability and generalizability.

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The gut bacterium Extibacter muris produces secondary bile acids and influences liver physiology in gnotobiotic mice

Cited by 192 publications

References 95 publications

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

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

Metabolic reconstitution by a gnotobiotic microbiota varies over the circadian cycle

Health Monitoring of Laboratory Rodent Colonies—Talking about (R)evolution

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