Gut Microbiome Variation Modulates the Effects of Dietary Fiber on Host Metabolism

Abstract BackgroundThere is general consensus that consumption of dietary fermentable fiber improves cardiometabolic health, in part by promoting mutualistic microbes and by increasing production of beneficial metabolites in the distal gut. However, human studies have reported variations in the observed benefits among individuals consuming the same fiber.Several factors likely contribute to this variation, including host genetic and gut microbial differences. We hypothesized that gut microbial metabolism of dietary fiber represents an important and differential factor that modulates how dietary fiber impacts the host.ResultsWe examined genetically identical gnotobiotic mice harboring two distinct complex gut microbial communities and exposed to four isocaloric diets, each containing different fibers: (i) cellulose, (ii) inulin, (iii) pectin, (iv) a mix of 5 fermentable fibers (assorted fiber). Gut microbiome analysis showed that each transplanted community preserved a core of common taxa across diets that differentiated it from the other community, but there were variations in richness and bacterial taxa abundance within each community among the different diet treatments. Host epigenetic, transcriptional and metabolomic analyses revealed diet-directed differences between microbiome groups, including variation in amino acids and lipid pathways that were associated with divergent health outcomes.ConclusionThis study demonstrates that interindividual variation in the gut microbiome is causally linked to differential effects of dietary fiber on host metabolic phenotypes and suggests that a one-fits-all fiber supplementation approaches to promote health is unlikely to elicit consistent effects across individuals Overall, the presented results underscore the importance of microbe-diet interactions on host metabolism and suggest that gut microbes modulate dietary fiber efficacy.

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Gut microbiome variation modulates the effects of dietary fiber on host metabolism

Microbiome ◽

10.1186/s40168-021-01061-6 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Sofia M. Murga-Garrido ◽

Qilin Hong ◽

Tzu-Wen L. Cross ◽

Evan R. Hutchison ◽

Jessica Han ◽

...

Keyword(s):

Dietary Fiber ◽

Gut Microbiome ◽

Interindividual Variation ◽

Cardiometabolic Health ◽

Metabolic Phenotypes ◽

Microbiome Analysis ◽

Host Genetic ◽

Gnotobiotic Mice ◽

Isocaloric Diets ◽

Host Metabolism

Abstract Background There is general consensus that consumption of dietary fermentable fiber improves cardiometabolic health, in part by promoting mutualistic microbes and by increasing production of beneficial metabolites in the distal gut. However, human studies have reported variations in the observed benefits among individuals consuming the same fiber. Several factors likely contribute to this variation, including host genetic and gut microbial differences. We hypothesized that gut microbial metabolism of dietary fiber represents an important and differential factor that modulates how dietary fiber impacts the host. Results We examined genetically identical gnotobiotic mice harboring two distinct complex gut microbial communities and exposed to four isocaloric diets, each containing different fibers: (i) cellulose, (ii) inulin, (iii) pectin, (iv) a mix of 5 fermentable fibers (assorted fiber). Gut microbiome analysis showed that each transplanted community preserved a core of common taxa across diets that differentiated it from the other community, but there were variations in richness and bacterial taxa abundance within each community among the different diet treatments. Host epigenetic, transcriptional, and metabolomic analyses revealed diet-directed differences between animals colonized with the two communities, including variation in amino acids and lipid pathways that were associated with divergent health outcomes. Conclusion This study demonstrates that interindividual variation in the gut microbiome is causally linked to differential effects of dietary fiber on host metabolic phenotypes and suggests that a one-fits-all fiber supplementation approach to promote health is unlikely to elicit consistent effects across individuals. Overall, the presented results underscore the importance of microbe-diet interactions on host metabolism and suggest that gut microbes modulate dietary fiber efficacy.

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54Role of the gut microbiome for the cholesterol lowering effect of atorvastatin

European Heart Journal ◽

10.1093/eurheartj/ehz747.0007 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

F Zimmermann ◽

D Schmidt ◽

U Escher ◽

A Jasina ◽

J Roessler ◽

...

Keyword(s):

Gut Microbiome ◽

Cholesterol Synthesis ◽

Interindividual Variation ◽

Hepatic Cholesterol ◽

Atorvastatin Treatment ◽

Hepatic Cholesterol Synthesis ◽

Lowering Effect ◽

Expression Of Genes ◽

Gnotobiotic Mice

Abstract Background and aims Statins show interindividual differences in the extent of low-density lipoprotein cholesterol (LDL-C) reduction. The mechanisms of this interindividual variation are not fully understood. Here, we examined the potential role of the gut microbiome for the LDL-C lowering property of atorvastatin. Methods Mice (C57BL/6) with either intact (conventional mice, CONV, n=24) or with antiobiotic depleted gut microbiome (gnotobiotic, n=16), were put on standard chow diet (SCD) (n=11) or high fat diet (HFD) (n=29) for 6 weeks. During the last 4 weeks atorvastatin (Ator, 10mg/kg body weight/day) or control vehicle was orally applied via gavage. Blood levels of LDL-C and glucose and body weight after 6 weeks of treatment were compared between the groups. Expression of genes involved in hepatic and intestinal cholesterol-metabolism were examined. Faeces of CONV mice were analyzed for alteration of the gut microbiota profile upon atorvastatin treatment using 16S rRNA qPCR. Results HFD fed mice with intact gut microbiome showed significantly increased blood LDL-C levels as compared to SCD (HFD: 36.8±1.4 mg/dl vs. SCD: 22.0±1.8 mg/dl; P<0.01). Bodyweight gain or blood glucose levels after HFD were not significantly different between CONV and gnotobiotic mice. While in CONV mice atorvastatin significantly reduced LDL-C levels after HFD, in gnotobiotic mice the LDL-C lowering effect of atorvastatin was attenuated (CONV+HFD+Ator: 31.0±1.8 mg/dl vs. gnotobiotic mice+HFD+Ator: 46.4±3 mg/dl; P<0.01). The expression of genes involved in hepatic cholesterol synthesis was not significantly altered in gnotobiotic mice as compared to CONV mice. In CONV mice HFD decreased the relative abundance of the bacterial phyla Bacteroidetes and increased the abundance of Firmicutes as compared to SCD. The ratio between Firmicutes to Bacteroidetes was shifted towards control conditions upon atorvastatin treatment. Conclusions The results of this study suggest a regulatory impact of atorvastatin on the gut-microbial profile and, in turn, a crucial role of the gut-microbiome for the LDL-C lowering effect of atorvastatin independent of its regulation of hepatic cholesterol synthesis. Our findings provide novel insight into potential microbiota-related mechanisms causing interindividual variation in LDL-C lowering effects of statins. Acknowledgement/Funding German Heart Research Foundation

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Faculty Opinions recommendation of The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.14176957.15682057 ◽

2012 ◽

Author(s):

Anne Salonen

Keyword(s):

Gut Microbiome ◽

Monozygotic Twins ◽

Fermented Milk ◽

Gnotobiotic Mice ◽

The Impact

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Impacts of PBDE-47 exposure before, during and after pregnancy on the maternal gut microbiome and its association with host metabolism

Ecotoxicology and Environmental Safety ◽

10.1016/j.ecoenv.2021.112530 ◽

2021 ◽

Vol 222 ◽

pp. 112530

Author(s):

Hui Gao ◽

Xueyan Wan ◽

Boya Xiao ◽

Kaichao Yang ◽

Yafei Wang ◽

...

Keyword(s):

Gut Microbiome ◽

Host Metabolism

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Carbohydrates great and small, from dietary fiber to sialic acids: How glycans influence the gut microbiome and affect human health

Gut Microbes ◽

10.1080/19490976.2020.1869502 ◽

2021 ◽

Vol 13 (1) ◽

pp. 1-18

Author(s):

Joanna K Coker ◽

Oriane Moyne ◽

Dmitry A. Rodionov ◽

Karsten Zengler

Keyword(s):

Human Health ◽

Dietary Fiber ◽

Gut Microbiome ◽

Sialic Acids

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Impact of the gut microbiome on the atorvastatin-dependent modulation of the serum lipidome

European Heart Journal ◽

10.1093/ehjci/ehaa946.3823 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

J Roessler ◽

F Zimmermann ◽

D Schmidt ◽

U Escher ◽

A Jasina ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

Gut Microbiome ◽

Interindividual Variation ◽

Funding Source ◽

Microbial Composition ◽

Atorvastatin Treatment ◽

Qrt Pcr ◽

16S Rna ◽

Regulatory Properties

Abstract Background and aims The modulation of serum lipids, in particular of the low-density lipoprotein cholesterol (LDL-C), by statins varies between individuals. The mechanisms regulating this interindividual variation are only poorly understood. Here, we investigated the relation between the gut microbiome and the regulatory properties of atorvastatin on the serum lipidome using mice with depleted gut microbiome. Methods Over a period of 6 weeks, mice (C57BL/6) with either an intact (conventional mice, CONV, n=24) or antibiotic-based depleted gut microbiome (antibiotic treated mice, ABS, n=16) were put on standard chow diet (SCD) or high fat diet (HFD), respectively. During the last 4 weeks of treatment atorvastatin (Ator, 10mg/kg body weight/day) or control vehicle was administered via daily oral gavage. Blood lipids (total cholesterol, VLDL, LDL-C, HDL-C) and serum sphingolipids were compared among the groups. The expressions of hepatic and intestinal genes involved in cholesterol metabolism were analyzed by qRT-PCR. Alterations in the gut microbiota profile of mice with intact gut microbiome were examined using 16S RNA qRT-PCR. Results In CONV mice, HFD led to significantly increased blood LDL-C levels as compared with SCD (HFD: 36.8±1.4 mg/dl vs. SCD: 22.0±1.8 mg/dl; P<0.01). In CONV mice atorvastatin treatment significantly reduced blood LDL-C levels after HFD, whereas in ABS mice the LDL-C lowering effect of atorvastatin was markedly attenuated (CONV+HFD+Ator: 31.0±1.8 mg/dl vs. ABS+HFD+Ator: 46.4±3 mg/dl; P<0.01). A significant reduction in the abundance of several plasma lipids, in particular sphingolipids and glycerophospholipids upon atorvastatin treatment was observed in CONV mice, but not in ABS mice. The expressions of distinct hepatic and intestinal cholesterol-regulating genes (ldlr, srebp2, pcsk9 and npc1l1) upon atorvastatin treatment were significantly altered in gut microbiota depleted mice. In response to HFD a decrease in the relative abundance of the bacterial phyla Bacteroides and an increase in the relative abundance of Firmicutes was observed. The altered ratio between Bacteroides and Firmicutes in HFD fed mice was partly reversed upon atorvastatin treatment. Conclusions Our findings indicate a crucial role of the gut microbiome for the regulatory properties of atorvastatin on the serum lipidome and, in turn, support a critical impact of atorvastatin on the gut microbial composition. The results provide novel insights into potential microbiota related mechanisms underlying interindividual variation in modulation of the serum lipidome by statins, given interindividual differences in microbiome composition and function. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): German Heart Research Foundation

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