scholarly journals Secondary bile acid ursodeoxycholic acid alters weight, the gut microbiota, and the bile acid pool in conventional mice

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246161
Author(s):  
Jenessa A. Winston ◽  
Alissa Rivera ◽  
Jingwei Cai ◽  
Andrew D. Patterson ◽  
Casey M. Theriot
Keyword(s):  
Community Structure ◽  
Bile Acid ◽  
Microbial Community ◽  
Gut Microbiota ◽  
Ursodeoxycholic Acid ◽  
Microbial Community Structure ◽  
Cecal Content ◽  
Bile Acid Pool ◽  
Acid Pool ◽  
Gut Microbial Community

Ursodeoxycholic acid (commercially available as ursodiol) is a naturally occurring bile acid that is used to treat a variety of hepatic and gastrointestinal diseases. Ursodiol can modulate bile acid pools, which have the potential to alter the gut microbiota community structure. In turn, the gut microbial community can modulate bile acid pools, thus highlighting the interconnectedness of the gut microbiota-bile acid-host axis. Despite these interactions, it remains unclear if and how exogenously administered ursodiol shapes the gut microbial community structure and bile acid pool in conventional mice. This study aims to characterize how ursodiol alters the gastrointestinal ecosystem in conventional mice. C57BL/6J wildtype mice were given one of three doses of ursodiol (50, 150, or 450 mg/kg/day) by oral gavage for 21 days. Alterations in the gut microbiota and bile acids were examined including stool, ileal, and cecal content. Bile acids were also measured in serum. Significant weight loss was seen in mice treated with the low and high dose of ursodiol. Alterations in the microbial community structure and bile acid pool were seen in ileal and cecal content compared to pretreatment, and longitudinally in feces following the 21-day ursodiol treatment. In both ileal and cecal content, members of the Lachnospiraceae Family significantly contributed to the changes observed. This study is the first to provide a comprehensive view of how exogenously administered ursodiol shapes the healthy gastrointestinal ecosystem in conventional mice. Further studies to investigate how these changes in turn modify the host physiologic response are important.

scholarly journals Secondary bile acid ursodeoxycholic acid (UDCA) alters weight, the gut microbiota, and the bile acid pool in conventional mice

2019 ◽  
Author(s):  
Jenessa A. Winston ◽  
Alissa Rivera ◽  
Jingwei Cai ◽  
Andrew D. Patterson ◽  
Casey M. Theriot
Keyword(s):  
Community Structure ◽  
Bile Acid ◽  
Microbial Community ◽  
Gut Microbiota ◽  
Ursodeoxycholic Acid ◽  
Microbial Community Structure ◽  
Cecal Content ◽  
Bile Acid Pool ◽  
Acid Pool ◽  
Gut Microbial Community

AbstractUrsodeoxycholic acid (commercially available as Ursodiol) is a naturally occurring bile acid that is used to treat a variety of hepatic and gastrointestinal diseases. Ursodiol can modulate bile acid pools, which have the potential to alter the gut microbiota community structure. In turn, the gut microbial community can modulate bile acid pools, thus highlighting the interconnectedness of the gut microbiota-bile acid-host axis. Despite these interactions, it remains unclear if and how exogenously administered ursodiol shapes the gut microbial community structure and bile acid pool. This study aims to characterize how ursodiol alters the gastrointestinal ecosystem in conventional mice. C57BL/6J wildtype mice were given one of three doses of ursodiol (50, 150, or 450 mg/kg/day) by oral gavage for 21 days. Alterations in the gut microbiota and bile acids were examined including stool, ileal, and cecal content. Bile acids were also measured in serum. Significant weight loss was seen in mice treated with the low and high dose of ursodiol. Alterations in the microbial community structure and bile acid pool were seen in ileal and cecal content compared to pretreatment, and longitudinally in feces following the 21-day ursodiol treatment. In both ileal and cecal content, members of the Lachnospiraceae family significantly contributed to the changes observed. This study is the first to provide a comprehensive view of how exogenously administered ursodiol shapes the gastrointestinal ecosystem. Further studies to investigate how these changes in turn modify the host physiologic response are important.ImportanceUrsodeoxycholic acid (commercially available as ursodiol) is used to treat a variety of hepatic and gastrointestinal diseases. Despite its widespread use, how ursodiol impacts the gut microbial community structure and bile acid pool remains unknown. This study is the first to provide a comprehensive view of how exogenously administered ursodiol shapes the gastrointestinal ecosystem. Ursodiol administration in conventional mice resulted in significant alterations in the gut microbial community structure and bile acid pool, indicating that ursodiol has direct impacts on the gut microbiota-bile acid-host axis which should be considered when this medication is administered.Bile Acid AbbreviationsαMCA – α–Muricholic acid; βMCA –β–Muricholic acid; ωMCA –ω–Muricholic acid; CA – Cholic acid; CDCA – Chenodeoxycholic acid; DCA – Deoxycholic acid; GCDCA – Glycochenodeoxycholic acid; GDCA – Glycodeoxycholic acid; GLCA – Glycolithocholic acid; GUDCA – Glycoursodeoxycholic acid; HCA – Hyodeoxycholic acid; iDCA – Isodeoxycholic acid; iLCA – Isolithocholic acid; LCA – Lithocholic acid; TCA – Taurocholic acid; TCDCA – Taurochenodeoxycholic acid; TDCA – Taurodeoxycholic acid; THCA – Taurohyodeoxycholic acid; TUDCA – Tauroursodeoxycholic acid; TβMCA – Tauro-β-muricholic acid; TωMCA –Tauro ω-muricholic acid; UDCA – Ursodeoxycholic acid.

scholarly journals 0243 Sleep-Wake Patterns during Infancy are Associated with Gut Microbial Community Structure in Toddlerhood

SLEEP ◽  
2019 ◽  
Vol 42 (Supplement_1) ◽  
pp. A100-A100
Author(s):  
Megan E Petrov ◽  
Corrie M Whisner ◽  
David McCormick ◽  
Michael Todd ◽  
Elizabeth Reifsnider
Keyword(s):  
Community Structure ◽  
Microbial Community ◽  
Microbial Community Structure ◽  
Wake Patterns ◽  
Gut Microbial Community

scholarly journals Comparative Metagenomic Analysis of Chicken Gut Microbial Community, Function, and Resistome to Evaluate Noninvasive and Cecal Sampling Resources

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1718
Author(s):  
Kelang Kang ◽  
Yan Hu ◽  
Shu Wu ◽  
Shourong Shi
Keyword(s):  
Community Structure ◽  
Microbial Community ◽  
Microbial Community Structure ◽  
Fecal Microbiota ◽  
Metagenomic Analysis ◽  
Fecal Samples ◽  
Microbial Community Function ◽  
Community Function ◽  
Rectal Swabs ◽  
Gut Microbial Community

When conducting metagenomic analysis on gut microbiomes, there is no general consensus concerning the mode of sampling: non-contact (feces), noninvasive (rectal swabs), or cecal. This study aimed to determine the feasibility and comparative merits and disadvantages of using fecal samples or rectal swabs as a proxy for the cecal microbiome. Using broiler as a model, gut microbiomes were obtained from cecal, cloacal, and fecal samples and were characterized according to an analysis of the microbial community, function, and resistome. Cecal samples had higher microbial diversity than feces, while the cecum and cloaca exhibited higher levels of microbial community structure similarity compared with fecal samples. Cecal microbiota possessed higher levels of DNA replicative viability than feces, while fecal microbiota were correlated with increased metabolic activity. When feces were excreted, the abundance of antibiotic resistance genes like tet and ErmG decreased, but some antibiotic genes became more prevalent, such as fexA, tetL, and vatE. Interestingly, Lactobacillus was a dominant bacterial genus in feces that led to differences in microbial community structure, metabolism, and resistome. In conclusion, fecal microbiota have limited potential as a proxy in chicken gut microbial community studies. Thus, feces should be used with caution for characterizing gut microbiomes by metagenomic analysis.

The influence of rosuvastatin on the gastrointestinal microbiota and host gene expression profiles

2017 ◽  
Vol 312 (5) ◽  
pp. G488-G497 ◽  
Author(s):  
J. A. Nolan ◽  
P. Skuse ◽  
K. Govindarajan ◽  
E. Patterson ◽  
N. Konstantinidou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Community Structure ◽  
Bile Acid ◽  
Microbial Community ◽  
Gut Microbiota ◽  
Acid Metabolism ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Bile Acid Metabolism ◽  
Gastrointestinal Microbiota

Statins are the most widely prescribed medications worldwide for the treatment of hypercholesterolemia. They inhibit the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-R), an enzyme involved in cholesterol synthesis in higher organisms and in isoprenoid biosynthesis in some bacteria. We hypothesized that statins may influence the microbial community in the gut through either direct inhibition or indirect mechanisms involving alterations to host responses. We therefore examined the impact of rosuvastatin (RSV) on the community structure of the murine gastrointestinal microbiota. RSV was orally administered to mice and the effects on the gut microbiota, host bile acid profiles, and markers of inflammation were analyzed. RSV significantly influenced the microbial community in both the cecum and feces, causing a significant decrease in α-diversity in the cecum and resulting in a reduction of several physiologically relevant bacterial groups. RSV treatment of mice significantly affected bile acid metabolism and impacted expression of inflammatory markers known to influence microbial community structure (including RegIIIγ and Camp) in the gut. This study suggests that a commonly used statin (RSV) leads to an altered gut microbial composition in normal mice with attendant impacts on local gene expression profiles, a finding that should prompt further studies to investigate the implications of statins for gut microbiota stability and health in humans. NEW & NOTEWORTHY This work demonstrates that rosuvastatin administration in mice affects the gastrointestinal microbiota, influences bile acid metabolism, and alters transcription of genes encoding factors involved in gut homeostasis and immunity in the gastrointestinal tract.

scholarly journals A metabolic pathway for bile acid dehydroxylation by the gut microbiome

2019 ◽  
Author(s):  
Masanori Funabashi ◽  
Tyler L. Grove ◽  
Victoria Pascal ◽  
Yug Varma ◽  
Molly E. McFadden ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Lithocholic Acid ◽  
Primary Biliary Cholangitis ◽  
Bile Acid Pool ◽  
Secondary Bile Acid ◽  
Acid Pool ◽  
Road Map ◽  
Host Physiology

ABSTRACTThe gut microbiota synthesize hundreds of molecules, many of which are known to impact host physiology. Among the most abundant metabolites are the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA), which accumulate at ~500 μM and are known to block C. difficile growth1, promote hepatocellular carcinoma2, and modulate host metabolism via the GPCR TGR53. More broadly, DCA, LCA and their derivatives are a major component of the recirculating bile acid pool4; the size and composition of this pool are a target of therapies for primary biliary cholangitis and nonalcoholic steatohepatitis. Despite the clear impact of DCA and LCA on host physiology, incomplete knowledge of their biosynthetic genes and a lack of genetic tools in their native producer limit our ability to modulate secondary bile acid levels in the host. Here, we complete the pathway to DCA/LCA by assigning and characterizing enzymes for each of the steps in its reductive arm, revealing a strategy in which the A-B rings of the steroid core are transiently converted into an electron acceptor for two reductive steps carried out by Fe-S flavoenzymes. Using anaerobic in vitro reconstitution, we establish that a set of six enzymes is necessary and sufficient for the 8-step conversion of cholic acid to DCA. We then engineer the pathway into Clostridium sporogenes, conferring production of DCA and LCA on a non-producing commensal and demonstrating that a microbiome-derived pathway can be expressed and controlled heterologously. These data establish a complete pathway to two central components of the bile acid pool, and provide a road map for deorphaning and engineering pathways from the microbiome as a critical step toward controlling the metabolic output of the gut microbiota.

scholarly journals Impacts of diets fed after weaning on gut microbiota and susceptibility to DSS-induced colitis in mice

2019 ◽  
Author(s):  
Yu Meng ◽  
Xiaojun Li ◽  
Shuijiao Chen ◽  
Fujun Li ◽  
Yani Yin ◽  
...  
Keyword(s):  
Community Structure ◽  
Microbial Community ◽  
Gut Microbiota ◽  
Microbial Community Structure ◽  
High Protein ◽  
High Fiber ◽  
High Sugar ◽  
Fiber Protein ◽  
Protein Fiber ◽  
Protein Group

AbstractBackgroundLiving in a sanitary environment and taking Western-style diet in early life are both risk factors for inflammatory bowel disease and important factors for shaping host gut microbiota. Here, we aimed to establish whether different dietary composition fed during the early period after weaning would associate the susceptibility to DSS-induced colitis with different gut microbiota shifts.MethodsEighty weaned Balb/c mice were fed with high sugar, fat, protein, fiber, and standard diet for 8weeks respectively. Inflammation was induced by administration of 2.5% (wt/vol) dextran sulfate sodium (DSS) in drinking water for 7 days, and the microbiota characterized by 16s rRNA based pyrosequencing. Analyzed the inflammatory factors and toll-like receptors by Real-time PCRResultsThe high protein and high fiber+protein group exacerbated severity of DSS-induced colitis, the high fiber and high protein+fiber groups had the effect of reducing colitis, and the high sugar, fat and standard group show the similar disease phenotype of colitis. The diversity and richness of the microflora were significantly decreased in the high fiber group, while only decreased richness of flora was observed in the high protein group. The abundance of Firmicutes was decreased and the abundance of Bacteroides was increased in the high fat, high sugar, high protein and high fiber groups, especially in the high protein and high fiber group. The microbial community structure was slightly different at the species/genus level. The microbial community structure of high protein-fiber group and high fiber-protein group was still similar.ConclusionsMice were fed with different dietary compositions of high sugar, fat, protein and fiber diets since weaning, and similar gut microbiota of high-abundance Bacteroides and low-abundance Firmicutes are formed in adult mice. These microbiota do not cause colonic mucosal damage directly. Only high protein diet aggravated DSS-induced colitis, while high fiber diet alleviated the colitis.

scholarly journals Macrobdella decora: Old World Leech Gut Microbial Community Structure Conserved in a New World Leech

2019 ◽  
Author(s):  
Emily Ann McClure ◽  
Michael C. Nelson ◽  
Amy Lin ◽  
Joerg Graf
Keyword(s):  
Animal Model ◽  
Community Structure ◽  
Microbial Community ◽  
Microbial Community Structure ◽  
Medicinal Leech ◽  
Easy Access ◽  
Macrobdella Decora ◽  
Hirudo Verbana ◽  
Geographic Separation ◽  
Gut Microbial Community

ABSTRACTLeeches are found in terrestrial, aquatic, and marine habitats on all continents. Sanguivorous leeches have been used in medicine for millennia. Modern scientific uses include studies of neurons, anticoagulants, and gut microbial symbioses.Hirudo verbana, the European medicinal leech, maintains a gut community dominated by two bacterial symbionts,Aeromonas veroniiandMucinivorans hirudinis, which sometimes account for as much as 97% of the total crop microbiota. The highly simplified gut anatomy and microbiome ofH. verbanamake it an excellent model organism for studying gut microbial dynamics. The North American medicinal leech,Macrobdella decora,is a hirudinid leech native to Canada and the northern U.S.A. In this study we show thatM. decorasymbiont communities are very similar to those inH. verbana.This similarity allowed for an extensive study in which wild caught animals were sampled to determine effects of geographic separation, time of collection, and feeding on the microbiome. Through 16S V4 rRNA deep sequencing we show that: i) theM. decoragut and bladder microbial communities are distinct, ii) theM. decoragut community is affected by feeding and long periods of starvation, and iii) geographic separation does not appear to affect the overall gut microbial community structure. We propose thatM. decorais a replacement forH. verbanafor studies of wild-caught animals and offer evidence for the conservation of annelid symbionts. Successful culturing and comparison of dominant symbionts fromM. decoraandH. verbenawill provide the ability to assess host-symbiont co-evolution in future work.IMPORTANCEBuilding evidence implicates the gut microbiome in regulating animal digestion, nutritional acquisition, immune regulation, development, and even mood regulation. Because of the difficulty of assigning causative relationships in complex gut microbiomes a simplified model for testing hypotheses is necessary. Previous research inHirudo verbanahas suggested this animal as a highly simplified and tractable animal model of gut symbioses. Our data show thatMacrobdella decoramay work just as well asH. verbanawithout the drawback of being an endangered organism and with the added convenience of easy access to field-caught specimens. The similarity of the microbial community structure of species from two different continents reveals the highly-conserved nature of the microbial symbionts in sanguivorous leeches and confirms the medicinal leech as a highly simplified, natural animal model in which to study gut symbioses.

Bacterial deconjugation and enterohepatic circulation of norursocholic acid conjugates in rats

1991 ◽  
Vol 261 (6) ◽  
pp. G1065-G1071
Author(s):  
J. Lillienau ◽  
B. Borgstrom
Keyword(s):  
Bile Acid ◽  
Enterohepatic Circulation ◽  
Cecal Content ◽  
Acid Biosynthesis ◽  
Bile Acid Pool ◽  
Distal Small Intestine ◽  
Acid Pool ◽  
System 2 ◽  
Small Intestinal

Experiments were performed to define the metabolism of norusocholic acid (nUC) conjugates and to quantify to what extent the bile acid pool can be enriched in these bile acids. In vitro incubations of norusocholylglycine (nUCG) and -taurine (nUCT) with small intestinal or cecal content showed deconjugation with only cecal content. Cholylglycine (CG) was deconjugated by small intestinal and cecal content. Infusion of nUCG and CG showed that only a small proportion of nUCG was deconjugated after 24 h of enterohepatic circulation, whereas all CG was deconjugated. When nUCT was administered orally, deconjugation was shown to take place mainly in the cecum. Chronic feeding of nUCT enriched the bile acid pool with only 20% nUCT. We conclude that nUC conjugates are deconjugated primarily by bacteria in the cecum and colon, in contrast to CG, which, in addition to cecum and colon, is deconjugated in the distal small intestine. nUCT and its metabolites do not enrich in the circulating bile acid pool mainly for the following reasons: 1) nUC conjugates have a low affinity for the ileal transport system; 2) nUC, even if formed by deconjugation, is not passively absorbed at a sufficient rate; 3) the small amount of norursodeoxycholic acid formed from nUC is glucuronidated in the liver and glucuronide conjugates do not undergo enterohepatic circulation; and 4) nUC conjugates do not suppress bile acid biosynthesis.

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