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Gut Microbiota Composition Is Associated With the Global DNA Methylation Pattern in Obesity.

ABSTRACT: Objective: Obesity and obesity-related metabolic diseases are characterized by gut microbiota and epigenetic alterations. Recent insight has suggested the existence of a crosstalk between the gut microbiome and the epigenome. However, the possible link between alterations in gut microbiome composition and epigenetic marks in obesity has been not explored yet. The aim of this work is to establish a link between the gut microbiota and the global DNA methylation profile in a group of obese subjects and to report potential candidate genes that could be epigenetically regulated by gut microbiota in adipose tissue. Methods: Gut microbiota composition was analyzed in DNA stool samples from 45 obese subjects by 16S ribosomal RNA (rRNA) gene sequencing. Twenty patients were selected based on their Bacteroidetes-to-Firmicutes ratio (BFR): HighBFR group (BFR > 2.5, n = 10) and LowBFR group (BFR < 1.2, n = 10). Genome-wide analysis of DNA methylation pattern in both whole blood and visceral adipose tissue of these selected patients was performed with an Infinium EPIC BeadChip array-based platform. Gene expression analysis of candidate genes was done in adipose tissue by real-time quantitative PCR. Results: Genome-wide analysis of DNA methylation revealed a completely different DNA methylome pattern in both blood and adipose tissue in the low BFR group vs. the high BFR group. Two hundred fifty-eight genes were differentially methylated in both blood and adipose tissue, of which several potential candidates were selected for gene expression analysis. We found that in adipose tissue, both HDAC7 and IGF2BP2 were hypomethylated and overexpressed in the low BFR group compared with the high BFR group. ? values of both genes significantly correlated with the BFR ratio and the relative abundance of Bacteroidetes and/or Firmicutes. Conclusions: In this study, we demonstrate that the DNA methylation status is associated with gut microbiota composition in obese subjects and that the expression levels of candidate genes implicated in glucose and energy homeostasis (e.g., HDAC7 and IGF2BP2) could be epigenetically regulated by gut bacterial populations in adipose tissue.

SUBMITTER: Ramos-Molina B

PROVIDER: S-EPMC6616130 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Gut Microbiota Composition Is Associated With the Global DNA Methylation Pattern in Obesity.

Ramos-Molina Bruno B Sánchez-Alcoholado Lidia L Cabrera-Mulero Amanda A Lopez-Dominguez Raul R Carmona-Saez Pedro P Garcia-Fuentes Eduardo E Moreno-Indias Isabel I Tinahones Francisco J FJ

Frontiers in genetics 20190703

<b>Objective:</b> Obesity and obesity-related metabolic diseases are characterized by gut microbiota and epigenetic alterations. Recent insight has suggested the existence of a crosstalk between the gut microbiome and the epigenome. However, the possible link between alterations in gut microbiome composition and epigenetic marks in obesity has been not explored yet. The aim of this work is to establish a link between the gut microbiota and the global DNA methylation profile in a group of obese s ...[more]

PMID: 31333715

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Project description:BackgroundObesity is a complex pathology associated with dysbiosis, metabolic alterations, and low-grade chronic inflammation promoted by immune cells, infiltrating and populating the adipose tissue. Probiotic supplementation was suggested to be capable of counteracting obesity-associated immune and microbial alterations, based on its proven immunomodulatory activity and positive effect on gut microbial balance. Traditional fermented foods represent a natural source of live microbes, including environmental strains with probiotic features, which could transiently colonise the gut. The aim of our work was to evaluate the impact of supplementation with a complex foodborne bacterial consortium on obesity-associated inflammation and gut microbiota composition in a mouse model.MethodsC57BL/6J mice fed a 45% high fat diet (HFD) for 90 days were supplemented with a mixture of foodborne lactic acid bacteria derived from the traditional fermented dairy product "Mozzarella di Bufala Campana" (MBC) or with the commercial probiotic GG strain of Lactobacillus rhamnosus (LGG). Inflammation was assessed in epididymal white adipose tissue (WAT) following HFD. Faecal microbiota composition was studied by next-generation sequencing.ResultsSignificant reduction of epididymal WAT weight was observed in MBC-treated, as compared to LGG and control, animals. Serum metabolic profiling showed correspondingly reduced levels of triglycerides and higher levels of HDL cholesterol, as well as a trend toward reduction of LDL-cholesterol levels. Analysis of the principal leucocyte subpopulations in epididymal WAT revealed increased regulatory T cells and CD4+ cells in MBC microbiota-supplemented mice, as well as decreased macrophage and CD8+ cell numbers, suggesting anti-inflammatory effects. These results were associated with lower levels of pro-inflammatory cytokines and chemokines in WAT explants. Faecal bacterial profiling demonstrated increased Firmicutes/Bacteroidetes ratio in all mice groups following HFD.ConclusionsTaken together, these results indicate a protective effect of MBC microbiota supplementation toward HFD-induced fat accumulation and triglyceride and cholesterol levels, as well as inflammation, suggesting a stronger effect of a mixed microbial consortium vs single-strain probiotic supplementation. The immunomodulatory activity exerted by the MBC microbiota could be due to synergistic interactions within the microbial consortium, highlighting the important role of dietary microbes with yet uncharacterised probiotic effect.

Project description:The obesity epidemic is a global challenge, and the velocity of propagation is high in the population at reproductive age. Overweight and obesity during pregnancy have been associated with high birth weight and an increased risk of childhood obesity, reinforcing the risk of other non-communicable diseases. Obesity involves chronic low-grade systemic inflammation. New biomarkers for early detection of obesity risk are urgently required. The aim of this study was to identify the connection between pregestational BMI (pre-BMI) status and inflammatory biomarkers during the third trimester of pregnancy and their association with intestinal microbiota composition. Fifty-four pregnant women were classified according to pre-pregnancy BMI as normoweight, overweight, or obese. Weight gain, inflammatory biomarkers (hs_CRP, haptoglobin, and suPAR), and microbiota composition were assessed during the third trimester. A significant lower weight gain for obese mothers and a positive correlation between pre-BMI and inflammatory biomarkers were detected (Spearman's correlation). Haptoglobin levels were significantly higher in overweight and obese mothers. Higher Firmicutes levels and a higher ratio Firmicutes/Bacteroidetes were observed in the overweight and obese subjects. High hs_CRP and haptoglobin levels were also correlated with decreased microbiota diversity (Shannon index), whereas haptoglobin and hs_CRP values were correlated with several microbiota components, such as Ruminococcus gnavus and Faecalibacterium, and with specific phyla in the normoweight and overweight mothers; no significant associations with microbiota were found for suPAR. In conclusion, haptoglobin and hs_CRP reflected pregestational BMI status and related microbiota components, but haptoglobin was a better biomarker for microbiota associated with overweight. suPAR was associated with low grade inflammation dependent on pre-pregnancy BMI, but it was not related to deviated microbiota profiles.

Dataset Information

Gut Microbiota Composition Is Associated With the Global DNA Methylation Pattern in Obesity.

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Gut Microbiota Composition Is Associated With the Global DNA Methylation Pattern in Obesity.

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