Faecalibacterium prausnitzii phylotypes in type two diabetic, obese, and lean control subjects.

Faecalibacterium prausnitzii is one of the main butyrate producers in the healthy human gut. Information on its genetic diversity is lacking, although two genetic phylotypes have been differentiated. In the present study, F. prausnitzii phylotypes were examined in faeces of obese and type two diabetes with similar eating behaviour compared to a lean control group. The purpose of the study was to analyse if an excessive butyrate production induced by different F. prausnitzii phylotypes discriminates between obese developing type two diabetes or not. The faecal samples were analysed for the total abundance of F. prausnitzii 16S rRNA copies, fragment lengths polymorphism, high resolution melt curve analysis (HRM) and the butyryl-CoA:acetate CoA-transferase gene copies and melt curve variances. The diabetic group was found to differ significantly from the lean control group in the results of qPCR, butyryl-CoA:acetyate CoA-transferase gene melt curve, and HRM. F. prausnitzii phylotypes differed in obese with and without developed diabetes type two. Different phylotypes of F. prausnitzii may lead to differences in the inflammatory genesis in the host. F. prausnitzii phylotypes may have an influence on developing type two diabetes and might also act as starting points for prevention and therapy of obesity associated disease.

Gut microbiota composition correlates with changes in body fat content due to weight loss.

Genetics, lifestyle, and dietary habits contribute to metabolic syndrome, but also an altered gut microbiota has been identified. Based on this knowledge it is suggested that host bacterial composition tends to change in response to dietary factors and weight loss. The aim of this study was to identify bacteria affecting host metabolism in obesity during weight loss and to correlate them with changes of the body composition obtained from bioelectrical impedance analysis (BIA). We recruited obese individuals receiving a dietary intervention according DACH (German, Austrian, and Swiss Society of Nutrition) reference values and guidelines for 'prevention and therapy of obesity' of DAG e.V., DDG, DGE e.V., and DGEM e.V. over three months. Faecal microbiota and BIA measurements were conducted at three time points, before, during, and after the intervention. Gut microbiota was analysed on the basis of 16S rDNA with quantitative real time PCR. Additionally, a food frequency questionnaire with questions to nutritional behaviour, lifestyle, and physical activity was administered before intervention. After weight reduction, obese individuals showed a significant increase of total bacterial abundance. The ratio of Firmicutes/Bacteroidetes significantly decreased during intervention. Lactobacilli significantly increased between the first and the second time point. These differences also correlated with differences in weight percentage. During the intervention period Clostridium cluster IV increased significantly between the second and the third time point. In contrast Clostridium cluster XIVa showed a decreased abundance. The dominant butyrate producer, Faecalibacterium prausnitzii, significantly increased as did the abundance of the butyryl-CoA: acetate CoA-transferase gene. Archaea and Akkermansia were significantly more prevalent after weight reduction. Our results show a clear difference in the gut bacterial composition before and after dietary intervention with a rapid change in gut microbial composition after a few weeks, but also indicate that a major shift requires long term dietary treatment.

Microbiota and epigenetic regulation of inflammatory mediators in type 2 diabetes and obesity.

Metabolic syndrome is associated with alterations in the structure of the gut microbiota leading to low-grade inflammatory responses. An increased penetration of the impaired gut membrane by bacterial components is believed to induce this inflammation, possibly involving epigenetic alteration of inflammatory molecules such as Toll-like receptors (TLRs). We evaluated changes of the gut microbiota and epigenetic DNA methylation of TLR2 and TLR4 in three groups of subjects: type 2 diabetics under glucagon-like peptide-1 agonist therapy, obese individuals without established insulin resistance, and a lean control group. Clostridium cluster IV, Clostridium cluster XIVa, lactic acid bacteria, Faecalibacterium prausnitzii and Bacteroidetes abundances were analysed by PCR and 454 high-throughput sequencing. The epigenetic methylation in the regulatory region of TLR4 and TLR2 was analysed using bisulfite conversion and pyrosequencing. We observed a significantly higher ratio of Firmicutes/ Bacteroidetes in type 2 diabetics compared to lean controls and obese. Major differences were shown in lactic acid bacteria, with the highest abundance in type 2 diabetics, followed by obese and lean participants. In comparison, F. prausnitzii was least abundant in type 2 diabetics, and most abundant in lean controls. Methylation analysis of four CpGs in the first exon of TLR4 showed significantly lower methylation in obese individuals, but no significant difference between type 2 diabetics and lean controls. Methylation of seven CpGs in the promoter region of TLR2 was significantly lower in type 2 diabetics compared to obese subjects and lean controls. The methylation levels of both TLRs were significantly correlated with body mass index. Our data suggest that changes in gut microbiota and thus cell wall components are involved in the epigenetic regulation of inflammatory reactions. An improved diet targeted to induce gut microbial balance and in the following even epigenetic changes of pro-inflammatory genes may be effective in the prevention of metabolic syndrome.