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Analysis of the gut microbiome and plasma short-chain fatty acid profiles in a spontaneous mouse model of metabolic syndrome.

ABSTRACT: Male Tsumura Suzuki obese diabetes (TSOD) mice spontaneously develop obesity and obesity-related metabolic syndrome. Gut dysbiosis, an imbalance of gut microbiota, has been implicated in the pathogenesis of metabolic syndrome, but its mechanisms are unknown. Short-chain fatty acids (SCFAs) are the main fermentation products of gut microbiota and a link between the gut microbiota and the host's physiology. Here, we investigated a correlation among gut dysbiosis, SCFAs, and metabolic syndrome in TSOD mice. We detected enriched levels of Gram-positive bacteria and corresponding decreases in Gram-negative bacteria in 24-wk-old metabolic syndrome-affected TSOD mice compared with age-matched controls. The abundance of Bacteroidetes species decreased, the abundance of Firmicutes species increased, and nine genera of bacteria were altered in 24-wk-old TSOD mice. The total plasma SCFA level was significantly lower in the TSOD mice than in controls. The major plasma SCFA-acetate-decreased in TSOD mice, whereas propionate and butyrate increased. TSOD mice had no minor SCFAs (valerate and hexanoate) but normal mice did. We thus concluded that gut dysbiosis and consequent disruptions in plasma SCFA profiles occurred in metabolic syndrome-affected TSOD mice. We also propose that the TSOD mouse is a useful model to study gut dysbiosis, SCFAs, and metabolic syndrome.

SUBMITTER: Nishitsuji K

PROVIDER: S-EPMC5696507 | biostudies-other | 2017 Nov

REPOSITORIES: biostudies-other

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Analysis of the gut microbiome and plasma short-chain fatty acid profiles in a spontaneous mouse model of metabolic syndrome.

Nishitsuji Kazuchika K Xiao Jinzhong J Nagatomo Ryosuke R Umemoto Hitomi H Morimoto Yuki Y Akatsu Hiroyasu H Inoue Koichi K Tsuneyama Koichi K

Scientific reports 20171120 1

Male Tsumura Suzuki obese diabetes (TSOD) mice spontaneously develop obesity and obesity-related metabolic syndrome. Gut dysbiosis, an imbalance of gut microbiota, has been implicated in the pathogenesis of metabolic syndrome, but its mechanisms are unknown. Short-chain fatty acids (SCFAs) are the main fermentation products of gut microbiota and a link between the gut microbiota and the host's physiology. Here, we investigated a correlation among gut dysbiosis, SCFAs, and metabolic syndrome in T ...[more]

PMID: 29158587

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Project description:ObjectiveTo determine the longer-term effects of metformin treatment and behavioral weight loss on gut microbiota and short-chain fatty acids (SCFAs).Research design and methodsWe conducted a 3-parallel-arm, randomized trial. We enrolled overweight/obese adults who had been treated for solid tumors but had no ongoing cancer treatment and randomized them (n = 121) to either 1) metformin (up to 2,000 mg), 2) coach-directed behavioral weight loss, or 3) self-directed care (control) for 12 months. We collected stool and serum at baseline (n = 114), 6 months (n = 109), and 12 months (n = 105). From stool, we extracted microbial DNA and conducted amplicon and metagenomic sequencing. We measured SCFAs and other biochemical parameters from fasting serum.ResultsOf the 121 participants, 79% were female and 46% were Black, and the mean age was 60 years. Only metformin treatment significantly altered microbiota composition. Compared with control, metformin treatment increased amplicon sequence variants for Escherichia (confirmed as Escherichia coli by metagenomic sequencing) and Ruminococcus torques and decreased Intestinibacter bartlettii at both 6 and 12 months and decreased the genus Roseburia, including R. faecis and R. intestinalis, at 12 months. Effects were similar in comparison of the metformin group with the behavioral weight loss group. Metformin versus control also increased butyrate, acetate, and valerate at 6 months (but not at 12 months). Behavioral weight loss versus control did not significantly alter microbiota composition but did increase acetate at 6 months (but not at 12 months). Increases in acetate were associated with decreases in fasting insulin. Additional whole genome metagenomic sequencing of a subset of the metformin group showed that metformin altered 62 metagenomic functional pathways, including an acetate producing pathway and three pathways in glucose metabolism.ConclusionsMetformin, but not behavioral weight loss, impacted gut microbiota composition at 6 months and 12 months. Both metformin and behavioral weight loss altered circulating SCFAs at 6 months, including increasing acetate, which correlated with lower fasting insulin. Future research is needed to elucidate whether the gut microboime mediates or modifies metformin's health effects.

Project description:BACKGROUND:While some of the variance observed in adiposity and weight change within populations can be accounted for by traditional risk factors, a new factor, the gut microbiota, has recently been associated with obesity. However, the causal mechanisms through which the gut microbiota and its metabolites, short chain fatty acids (SCFAs) influence obesity are unknown, as are the individual obesogenic effects of the individual SCFAs (butyrate, acetate and propionate). This study, METS-Microbiome, proposes to examine the influence of novel risk factors, the gut microbiota and SCFAs, on obesity, adiposity and weight change in an international established cohort spanning the epidemiologic transition. METHODS:The parent study; Modeling the Epidemiologic Transition Study (METS) is a well-established and ongoing prospective cohort study designed to assess the association between body composition, physical activity, and relative weight, weight gain and cardiometabolic disease risk in five diverse population-based samples in 2500 people of African descent. The cohort has been prospectively followed since 2009. Annual measures of obesity risk factors, including body composition, objectively measured physical activity and dietary intake, components which vary across the spectrum of social and economic development. In our new study; METS-Microbiome, in addition to continuing yearly measures of obesity risk, we will also measure gut microbiota and stool SCFAs in all contactable participants, and follow participants for a further 3 years, thus providing one of the largest gut microbiota population-based studies to date. DISCUSSION:This new study capitalizes upon an existing, extensively well described cohort of adults of African-origin, with significant variability as a result of the widespread geographic distributions, and therefore variation in the environmental covariate exposures. The METS-Microbiome study will substantially advance the understanding of the role gut microbiota and SCFAs play in the development of obesity and provide novel obesity therapeutic targets targeting SCFAs producing features of the gut microbiota. TRIAL REGISTRATION:Registered NCT03378765 Date first posted: December 20, 2017.

Dataset Information

Analysis of the gut microbiome and plasma short-chain fatty acid profiles in a spontaneous mouse model of metabolic syndrome.

Publications

Analysis of the gut microbiome and plasma short-chain fatty acid profiles in a spontaneous mouse model of metabolic syndrome.

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