Metagenomic sequencing of the human gut microbiome before and after bariatric surgery in obese patients with type 2 diabetes: correlation with inflammatory and metabolic parameters

Abstract

Roux-en-Y gastric bypass (RYGB) has become a prominent therapeutic option for long-term treatment of morbid obesity and type 2 diabetes mellitus (T2D). Cross talk and pathogenetic consequences of RYGB-induced profound effects on metabolism and gut microbiome are poorly understood. The aim of the present study therefore was to characterize intra-individual changes of gut microbial composition before and 3 months after RYGB by metagenomic sequencing in morbidly obese patients (body mass index (BMI)440 kg m À 2 ) with T2D. Subsequently, metagenomic data were correlated with clinical indices. Based on gene relative abundance profile, 1061 species, 729 genera, 44 phyla and 5127 KO (KEGG Orthology) were identified. Despite high diversity, bacteria could mostly be assigned to seven bacterial divisions. The overall metagenomic RYGB-induced shift was characterized by a reduction of Firmicutes and Bacteroidetes and an increase of Proteobacteria. Twenty-two microbial species and 11 genera were significantly altered by RYGB. Using principal component analysis, highly correlated species were assembled into two common components. Component 1 consisted of species that were mainly associated with BMI and C-reactive protein. This component was characterized by increased numbers of Proteobacterium Enterobacter cancerogenus and decreased Firmicutes Faecalibacterium prausnitzii and Coprococcus comes. Functional analysis of carbohydrate metabolism by KO revealed significant effects in 13 KOs assigned to phosphotransferase system. Spearmen's Rank correlation indicated an association of 10 species with plasma total-or low-density lipoprotein cholesterol, and 5 species with triglycerides. F. prausnitzii was directly correlated to fasting blood glucose. This is the first clinical demonstration of a profound and specific intra-individual modification of gut microbial composition by full metagenomic sequencing. A clear correlation exists of microbiome composition and gene function with an improvement in metabolic and inflammatory parameters. This will allow to develop new diagnostic and therapeutic strategies based on metagenomic sequencing of the human gut microbiome.

Influence of GABA and GABA-producing Lactobacillus brevis DPC 6108 on the development of diabetes in a streptozotocin rat model

“…Interestingly, thetreatment with high-GABA had the most pronouncedeffect on the relative proportions of Bacteroidetes andFirmicutes. Of course, the literature has implicated thisratio to be of significance in numerous disease states (Frank et al, 2011;Graessler et al, 2013). However, ourresults are in contrast to previous studies which havedescribed a decrease in the Firmicutes: Bacteroidetes ratioassociated with T1 D (Giongo et al, 2011; Murri et al,201 3).…”

Indication of Bariatric Surgery (Roux-en-Y Gastric Bypass Surgery and Vertical Gastrectomy) in The Older Individuals and implications For Gut Microbiota

“…Moreover, a change towards increased proteobacteria was observed, in particular E. cancerogenus, S. boydii and S. enterica, as well as a decline in butyrate formation produced by Firmicutes, such as F. prausnitzii, C. comes and A. caccae, induced by RYGB. These results may have long-term harmful effects on host health, with the potential risk of intestinal inflammation and colorectal carcinomas [11]. For this reason, the indication of RYGB in the elderly needs careful thought and a full evaluation of the risks and benefits of the surgery, especially as the results of research remain controversial.…”

“…Evidence has shown that modifications in the intestinal microbiota induced by RYGB and VG contributes to the reduction of weight and adipose tissue in the host, however, there is considerable change in the genera colonizing the intestine, which can trigger inflammatory and carcinogenic processes in the long term [11]. On the other hand, a diet rich in probiotics may aid in the restoration of beneficial microbiota and overall health of the elderly.…”

Does gastric bypass surgery change body weight set point?

“…The gut microbiome changes after gastric bypass surgery in humans, [66][67][68] rats 69 and mice, 70 and a recent transplant study in mice suggests that the changes in gut microbiome are responsible for at least some effects on body weight. 70 The signaling pathways leading from the microbiota in the intestinal lumen to reduced body weight are not known (Figure 3).…”