Dataset Information

The gut microbiota drives the impact of bile acids and fat source in diet on mouse metabolism.

ABSTRACT:

Background

As the gut microbiota contributes to metabolic health, it is important to determine specific diet-microbiota interactions that influence host metabolism. Bile acids and dietary fat source can alter phenotypes of diet-induced obesity, but the interplay with intestinal microorganisms is unclear. Here, we investigated metabolic consequences of diets enriched in primary bile acids with or without addition of lard or palm oil, and studied gut microbiota structure and functions in mice.

Results

In combination with bile acids, dietary lard fed to male C57BL/6N mice for a period of 8 weeks enhanced fat mass accumulation in colonized, but not in germ-free mice when compared to palm oil. This was associated with impaired glucose tolerance, lower fasting insulin levels, lower counts of enteroendocrine cells, fatty liver, and elevated amounts of hepatic triglycerides, cholesteryl esters, and monounsaturated fatty acids. Lard- and bile acid-fed mice were characterized by shifts in dominant gut bacterial communities, including decreased relative abundances of Lachnospiraceae and increased occurrence of Desulfovibrionaceae and the species Clostridium lactatifermentans and Flintibacter butyricus. Metatranscriptomic analysis revealed shifts in microbial functions, including lipid and amino acid metabolism.

Conclusions

Caution is required when interpreting data from diet-induced obesity models due to varying effects of dietary fat source. Detrimental metabolic consequences of a diet enriched with lard and primary bile acids were dependent on microbial colonization of the host and were linked to hepatic lipid rearrangements and to alterations of dominant bacterial communities in the cecum.

SUBMITTER: Just S

PROVIDER: S-EPMC6091023 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Publications

The gut microbiota drives the impact of bile acids and fat source in diet on mouse metabolism.

Just Sarah S Mondot Stanislas S Ecker Josef J Wegner Katrin K Rath Eva E Gau Laura L Streidl Theresa T Hery-Arnaud Genevieve G Schmidt Sinah S Lesker Till Robin TR Bieth Valentin V Dunkel Andreas A Strowig Till T Hofmann Thomas T Haller Dirk D Liebisch Gerhard G Gérard Philippe P Rohn Sascha S Lepage Patricia P Clavel Thomas T

Microbiome 20180802 1

<h4>Background</h4>As the gut microbiota contributes to metabolic health, it is important to determine specific diet-microbiota interactions that influence host metabolism. Bile acids and dietary fat source can alter phenotypes of diet-induced obesity, but the interplay with intestinal microorganisms is unclear. Here, we investigated metabolic consequences of diets enriched in primary bile acids with or without addition of lard or palm oil, and studied gut microbiota structure and functions in m ...[more]

PMID: 30071904

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Project description:IntroductionGestational diabetes mellitus (GDM) is a condition characterized by glucose intolerance during pregnancy, estimated to affect approximately 20% of the whole pregnancies and is increasing in prevalence globally. However, there is still a big gap in knowledge about the association between gut microbiota associated metabolism alterations and GDM development.MethodsAll the participants accomplished the validated internet-based dietary questionnaire for Chinese and serum, fecal samples were collected. HFD, control diet or colesevelam intervention was fed to GDM mice models or Fxr-/- mice models, with or without antibiotics cocktail treatment. Fecal microbiota transplantation were used for further validation. Gut microbiota and metabolites were detected by metagenomic sequencing and high-performance liquid chromatography-mass spectrometry, respectively. Bile acids of serum, fecal samples from human and mice were analysised. Body weight, average feed intake, blood glucose, insulin levels and oral glucose tolerance test was performed among each groups. Expression levels of Fxr, Shp and Fgf15 mRNA and protein were detected by quantitative reverse transcription polymerase chain reaction and western blot, respectively.ResultsOur data indicated that high fat diet (HFD) was linked with higher prevalence of GDM, and HFD was positively associated with poor prognosis in GDM patients. Moreover, compared with normal diet (ND) group, GDM patients from HFD group performed a loss of gut microbiota diversity and enrichment of Alistipes onderdonkii, Lachnospiraceae bacterium 1_7_58FAA, and Clostridium aspaaragiforme while ruduction of Akkermansiaceae, Paraprevotell xylaniphila, and Prevotella copri. Additionally, HFD aggravated GDM in mice and gut microbiota depletion by antibiotics crippled the effect of excess fat intake. BAs profile altered in HFD GDM patients and mice models. Fecal microbiota transplantation (FMT) further confirmed that gut microbiota contributed to bile acids (BAs) metabolic dysfunction during HFD-associated GDM development. Mechanically, HFD-FMT administration activated Fxr, Shp, and Fgf15 activity, disturbed the glucose metabolism and aggravated insulin resistance but not in HFD-FMT Fxr-/- mice and ND-FMT Fxr-/- mice. Furthermore, colesevelam intervention alleviated HFD-associated GDM development, improved BAs metabolism, suppressed Fxr, Shp, and Fgf15 activity only in WT mice but not in the Fxr-/- HFD + Colesevelam group and Fxr-/- HFD group. HFD induced GDM and contributed to poor prognosis in GDM parturients through inducing gut microbial dysbiosis and metabolic alteration, especially appeared in BAs profile. Moreover, Fxr pathway participated in regulating HFD-associated gut microbiota disordered BAs metabolites and aggravating GDM in mice.DiscussionModulating gut microbiota and BAs metabolites could be a potential therapeutic strategy in the prevention and treatment of HFD-associated GDM.

Project description:BackgroundMetabolic disorders have become one of the global medical problems. Due to the complexity of its pathogenesis, there is still no effective treatment. Bile acids (BAs) and gut microbiota (GM) have been proved to be closely related to host metabolism, which could be important targets for metabolic disorders. Zhi-Kang-Yin (ZKY) is a traditional Chinese medicine (TCM) formula developed by the research team according to theory of TCM and has been shown to improve metabolism in clinic. However, the underlying mechanisms are unclear.Aim of the studyThis study aimed to investigate the potential mechanisms of the beneficial effect of ZKY on metabolism.MethodsHigh-fat diet (HFD)-fed mice were treated with and without ZKY. The glucose and lipid metabolism-related indexes were measured. BA profile, GM composition and hepatic transcriptome were then investigated to analyze the changes of BAs, GM, and hepatic gene expression. Moreover, the relationship between GM and BAs was identified with functional gene quantification and ex vivo fermentation experiment.ResultsZKY reduced weight gain and lipid levels in both liver and serum, attenuated hepatic steatosis and improved glucose tolerance in HFD-fed mice. BA profile detection showed that ZKY changed the composition of BAs and increased the proportion of unconjugated BAs and non-12-OH BAs. Hepatic transcriptomic analysis revealed fatty acid metabolism and BA biosynthesis related pathways were regulated. In addition, ZKY significantly changed the structure of GM and upregulated the gene copy number of bacterial bile salt hydrolase. Meanwhile, ZKY directly promoted the growth of Bifidobacterium, which is a well-known bile salt hydrolase-producing genus. The ex vivo co-culture experiment with gut microbiota and BAs demonstrated that the changes of BAs profile in ZKY group were mediated by ZKY-shifted GM, which led to increased expression of genes associated with fatty acid degradation in the liver.ConclusionOur study indicated that the effect of ZKY on improving metabolism is associated with the modulation of GM-BAs axis, especially, by upregulating the abundance of bile salt hydrolase-expression bacteria and increasing the levels of unconjugated BAs. This study indicates that GM-BAs axis might be an important pathway for improving metabolic disorders by ZKY.

Dataset Information

The gut microbiota drives the impact of bile acids and fat source in diet on mouse metabolism.

Background

Results

Conclusions

Publications

The gut microbiota drives the impact of bile acids and fat source in diet on mouse metabolism.

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