Cross-Regional View of Functional and Taxonomic Microbiota Composition in Obesity and Post-obesity Treatment Shows Country Specific Microbial Contribution.
ABSTRACT: Gut microbiota has been shown to have an important influence on host health. The microbial composition of the human gut microbiota is modulated by diet and other lifestyle habits and it has been reported that microbial diversity is altered in obese people. Obesity is a worldwide health problem that negatively impacts the quality of life. Currently, the widespread treatment for obesity is bariatric surgery. Interestingly, gut microbiota has been shown to be a relevant factor in effective weight loss after bariatric surgery. Since that the human gut microbiota of normal subjects differs between geographic regions, it is possible that rearrangements of the gut microbiota in dysbiosis context are also region-specific. To better understand how gut microbiota contribute to obesity, this study compared the composition of the human gut microbiota of obese and lean people from six different regions and showed that the microbiota compositions in the context of obesity were specific to each studied geographic location. Furthermore, we analyzed the functional patterns using shotgun DNA metagenomic sequencing and compared the results with other obesity-related metagenomic studies, we observed that microbial contribution to functional pathways were country-specific. Nevertheless, our study showed that although microbial composition of obese patients was country-specific, the overall metabolic functions appeared to be the same between countries, indicating that different microbiota components contribute to similar metabolic outcomes to yield functional redundancy. Furthermore, we studied the microbiota functional changes of obese patients after bariatric surgery, by shotgun metagenomics sequencing and observed that changes in functional pathways were specific to the type of obesity treatment. In all, our study provides new insights into the differences and similarities of obese gut microbiota in relation to geographic location and obesity treatments.
Project description:<h4>Backgruound</h4>Current evidence support that the gut microbiota plays a potential role in obesity. Bariatric surgery can reduce excess weight and decrease the risk of life-threatening weight-related health problems and may also influence gut microbiota. In this study, we aimed to investigate the changes in gut microbiota before and after bariatric surgery and evaluate the association of the gut microbial shift and altered body mass index (BMI) after bariatric surgery.<h4>Methods</h4>Between January 2019 and July 2020, stools from 58 patients scheduled for bariatric surgery were collected. Six months after bariatric surgery, stools from 22 of these patients were re-collected, and the changes in gut microbiota before and after bariatric surgery were evaluated. In addition, the differences in gut microbiota between patients with severe obesity (BMI >35 kg/m2, n=42) and healthy volunteers with normal BMI (18.8 to 22.8 kg/m2, n=41) were investigated.<h4>Results</h4>The gut microbiota of patients who underwent bariatric surgery showed increased α-diversity and differed β-diversity compared with those before surgery. Interestingly, Blautia was decreased and Bacteriodes was increased at the genus level after bariatric surgery. Further, the Blautia/Bacteroides ratio showed a positive correlation with BMI. To validate these results, we compared the gut microbiota from severely obese patients with high BMI with those from healthy volunteers and demonstrated that the Blautia/Bacteroides ratio correlated positively with BMI.<h4>Conclusion</h4>In the gut microbial analysis of patients who underwent bariatric surgery, we presented that the Blautia/Bacteroides ratio had changed after bariatric surgery and showed a positive correlation with BMI.
Project description:OBJECTIVES:Decreased gut microbial gene richness (MGR) and compositional changes are associated with adverse metabolism in overweight or moderate obesity, but lack characterisation in severe obesity. Bariatric surgery (BS) improves metabolism and inflammation in severe obesity and is associated with gut microbiota modifications. Here, we characterised severe obesity-associated dysbiosis (ie, MGR, microbiota composition and functional characteristics) and assessed whether BS would rescue these changes. DESIGN:Sixty-one severely obese subjects, candidates for adjustable gastric banding (AGB, n=20) or Roux-en-Y-gastric bypass (RYGB, n=41), were enrolled. Twenty-four subjects were followed at 1, 3 and 12 months post-BS. Gut microbiota and serum metabolome were analysed using shotgun metagenomics and liquid chromatography mass spectrometry (LC-MS). Confirmation groups were included. RESULTS:Low gene richness (LGC) was present in 75% of patients and correlated with increased trunk-fat mass and comorbidities (type 2 diabetes, hypertension and severity). Seventy-eight metagenomic species were altered with LGC, among which 50% were associated with adverse body composition and metabolic phenotypes. Nine serum metabolites (including glutarate, 3-methoxyphenylacetic acid and L-histidine) and functional modules containing protein families involved in their metabolism were strongly associated with low MGR. BS increased MGR 1?year postsurgery, but most RYGB patients remained with low MGR 1?year post-BS, despite greater metabolic improvement than AGB patients. CONCLUSIONS:We identified major gut microbiota alterations in severe obesity, which include decreased MGR and related functional pathways linked with metabolic deteriorations. The lack of full rescue post-BS calls for additional strategies to improve the gut microbiota ecosystem and microbiome-host interactions in severe obesity. TRIAL REGISTRATION NUMBER:NCT01454232.
Project description:Obesity is one of the main worldwide public health concerns whose clinical management demands new therapeutic approaches. Bariatric surgery is the most efficient treatment when other therapies have previously failed. Due to the role of gut microbiota in obesity development, the knowledge of the link between bariatric surgery and gut microbiota could elucidate new mechanistic approaches. This study aims to evaluate the long-term effects of bariatric surgery in the faecal metagenome and metabolome of patients with severe obesity. Faecal and blood samples were collected before and four years after the intervention from patients with severe obesity. Biochemical, metagenomic and metabolomic analyses were performed and faecal short-chain fatty acids were measured. Bariatric surgery improved the obesity-related status of patients and significantly reshaped gut microbiota composition. Moreover, this procedure was associated with a specific metabolome profile characterized by a reduction in energetic and amino acid metabolism. Acetate, butyrate and propionate showed a significant reduction with bariatric surgery. Finally, correlation analysis suggested the existence of a long-term compositional and functional gut microbiota profile associated with the intervention. In conclusion, bariatric surgery triggered long-lasting effects on gut microbiota composition and faecal metabolome that could be associated with the remission of obesity.
Project description:Bariatric surgery is currently the most effective procedure for the treatment of obesity. Given the role of the gut microbiota in regulating host metabolism and adiposity, we investigated the long-term effects of bariatric surgery on the microbiome of patients randomized to Roux-en-Y gastric bypass or vertical banded gastroplasty and matched for weight and fat mass loss. The two surgical procedures induced similar and durable changes on the gut microbiome that were not dependent on body mass index and resulted in altered levels of fecal and circulating metabolites compared with obese controls. By colonizing germ-free mice with stools from the patients, we demonstrated that the surgically altered microbiota promoted reduced fat deposition in recipient mice. These mice also had a lower respiratory quotient, indicating decreased utilization of carbohydrates as fuel. Our results suggest that the gut microbiota may play a direct role in the reduction of adiposity observed after bariatric surgery.
Project description:Bariatric surgery is often the preferred method to resolve obesity and diabetes, with ∼800,000 cases worldwide yearly and high outcome variability. The ability to predict the long-term body mass index (BMI) change following surgery has important implications for individuals and the health care system in general. Given the tight connection between eating habits, sugar consumption, BMI, and the gut microbiome, we tested whether the microbiome before any treatment is associated with different treatment outcomes, as well as other intakes (high-density lipoproteins [HDL], triglycerides, etc.). A projection of the gut microbiome composition of obese (sampled before and after bariatric surgery) and lean patients into principal components was performed, and the relation between this projection and surgery outcome was studied. The projection revealed three different microbiome profiles belonging to lean, obese, and obese individuals who underwent bariatric surgery, with the postsurgery microbiome more different from the lean microbiome than the obese microbiome. The same projection allowed for a prediction of BMI loss following bariatric surgery, using only the presurgery microbiome. The microbial changes following surgery were an increase in the relative abundance of <i>Proteobacteria</i> and <i>Fusobacteria</i> and a decrease in <i>Firmicutes</i>. The gut microbiome can be decomposed into main components depicting the patient's development and predicting in advance the outcome. Those may be translated into the better clinical management of obese individuals planning to undergo metabolic surgery. <b>IMPORTANCE</b> BMI and diabetes can affect the gut microbiome composition. Bariatric surgery has large variabilities in the outcome. The microbiome was previously shown to be a good predictor for multiple diseases. We analyzed here the gut microbiome before and after bariatric surgery and showed the following. (i) The microbiome before surgery can be used to predict surgery outcomes. (ii) The postsurgery microbiome drifts further away from the lean microbiome than the microbiome of the presurgery obese patients. These results can lead to a microbiome-based presurgery decision whether to perform surgery.
Project description:BACKGROUND:Some of the metabolic effects of bariatric surgery may be mediated by the gut microbiome. OBJECTIVES:To study the effect of bariatric surgery on changes to gut microbiota composition and bacterial pathways, and their relation to metabolic parameters after bariatric surgery. SETTINGS:University hospitals in the United States and Spain. METHODS:Microbial diversity and composition by 16 S rRNA sequencing, putative bacterial pathways, and targeted circulating metabolites were studied in 26 individuals with severe obesity, with and without type 2 diabetes, before and at 3, 6, and 12 months after either gastric bypass or sleeve gastrectomy. RESULTS:Bariatric surgery tended to increase alpha diversity, and significantly altered beta diversity, microbiota composition, and function up to 6 months after surgery, but these changes tend to regress to presurgery levels by 12 months. Twelve of 15 bacterial pathways enriched after surgery also regressed to presurgery levels at 12 months. Network analysis identified groups of bacteria significantly correlated with levels of circulating metabolites over time. There were no differences between study sites, surgery type, or diabetes status in terms of microbial diversity and composition at baseline and after surgery. CONCLUSIONS:The association among changes in microbiome with decreased circulating biomarkers of inflammation, increased bile acids, and products of choline metabolism and other bacterial pathways suggest that the microbiome partially mediates improvement of metabolism during the first year after bariatric surgery.
Project description:<h4>Aim</h4>To explore how bariatric surgery (BS) modified the obesity-associated gut microbiome, the host metabolome, and their interactions in obese Korean patients.<h4>Materials and methods</h4>Stool and fasting blood samples were obtained before and 1, 3, 6, and 12 months after BS from 52 patients enrolled in the Korean Obesity Surgical Treatment Study. We analysed the gut microbiome by 16S rRNA gene sequencing and the serum metabolome, including bile acids, by nuclear magnetic resonance spectroscopy and ultrahigh-performance liquid chromatography/triple quadrupole mass spectrometry.<h4>Results</h4>Stool metagenomics showed that 27 microbiota were enriched and 14 microbiota were reduced after BS, whereas the abundances and diversity of observed features were increased. The levels of branched-chain amino acids and metabolites of energy metabolism in serum were decreased after surgery, whereas the levels of metabolites related to microbial metabolism, including dimethyl sulphone, glycine, and secondary bile acids, were increased in the serum samples. In addition, we found notable mutual associations among metabolites and gut microbiome changes attributed to BS.<h4>Conclusions</h4>Changes in the gut microbiome community and systemic levels of amino acids and sugars were directly derived from anatomical changes in the gastrointestinal tract after BS. We hypothesized that the observed increases in microbiome-related serum metabolites were a result of complex and indirect changes derived from BS. Ethnic-specific environmental or genetic factors could affect Korean-specific postmetabolic modification in obese patients who undergo BS.
Project description:<h4>Background</h4>Few studies have assessed differences in the gut microbiota composition after bariatric surgery in the long term or whether differences are correlated with remission of type 2 diabetes.<h4>Objectives</h4>This observational study assessed differences in the gut microbiota between individuals at up to 13 years after surgery and a comparison group of individuals with severe obesity. The relationship between type 2 diabetes remission and the gut microbiota was also assessed.<h4>Setting</h4>University.<h4>Methods</h4>Stool samples were collected from individuals completing bariatric surgery (surgery group; n = 16) and individuals with severe obesity that did not receive surgery (nonsurgery group; n = 19) as part of the 12-year follow-up in the Utah Obesity Study. Metabolic health data were collected at baseline and the follow-up examination. The gut microbiota was quantified by sequencing the V4 region of the 16 S rRNA gene. Significant differences in microbiota composition with surgery and other covariates were determined by Unifrac distance analysis and permutational multivariate analysis of variance. Significant differences in the relative abundance of individual bacterial taxa were assessed using analysis of composition of microbiomes software.<h4>Results</h4>The surgery group had higher relative abundances of Verrucomicrobiaceae (5.7 ± 1.3% versus 1.1 ± .3%) and Streptococcaceae (6.3 ± 1.0% versus 3.2 ± .8%), but lower relative abundances of Bacteroidaceae (8.8 ± 1.8% versus 18.6 ± 2.3%) 10.6 years after surgery. In a small subset of 8 individuals, a higher relative abundance of Akkermansia muciniphila was correlated with type 2 diabetes remission.<h4>Conclusions</h4>Differences in the gut microbiota are evident a decade after bariatric surgery compared with individuals with severe obesity that did not undergo surgery. The observed long-term differences are consistent with previous findings.
Project description:The modulation of the gut microbiota was recently deemed one of the mechanisms responsible for the excellent outcomes of bariatric surgery. However, to date, only few studies have assessed this, and they have high heterogeneity. In the present study, next-generation 16S ribosomal DNA amplicon sequencing was used to characterize the gut microbiota of healthy volunteers, as well as patients prior to and after sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). Significant differences in ? diversity, ? diversity and species were identified between the different groups/time-points. The results demonstrated excellent outcomes of SG and RYGB. The ? diversity was lower in healthy volunteers compared with that in morbidly obese patients with or without type 2 diabetes mellitus. At 3 months after SG, the ? diversity was increased and the ? diversity was decreased. The abundance of certain species changed significantly after SG and RYGB. It was also revealed that the abundance of certain microbes was significantly correlated with the body mass index, fasting blood glucose and glycosylated haemoglobin. It may be concluded that bariatric surgery may cause obvious alterations in the gut microbiota and compared with healthy volunteers and obese patients without bariatric surgery, the microbiota composition of post-bariatric surgery has unique characteristics. However, studies with a larger cohort and longer follow-up may be required to confirm these results.
Project description:Obesity levels, especially in children, have dramatically increased over the last few decades. Recently, several studies highlighted the involvement of gut microbiota in the pathophysiology of obesity. We investigated the composition of gut microbiota in obese adolescents and adults compared to age-matched normal weight (NW) volunteers in order to assemble age- and obesity-related microbiota profiles. The composition of gut microbiota was analyzed by 16S rRNA-based metagenomics. Ecological representations of microbial communities were computed, and univariate, multivariate, and correlation analyses performed on bacterial profiles. The prediction of metagenome functional content from 16S rRNA gene surveys was carried out. Ecological analyses revealed a dissimilarity among the subgroups, and resultant microbiota profiles differed between obese adolescents and adults. Using statistical analyses, we assigned, as microbial markers, Faecalibacterium prausnitzii and Actinomyces to the microbiota of obese adolescents, and Parabacteroides, Rikenellaceae, Bacteroides caccae, Barnesiellaceae, and Oscillospira to the microbiota of NW adolescents. The predicted metabolic profiles resulted different in adolescent groups. Particularly, biosynthesis of primary bile acid and steroid acids, metabolism of fructose, mannose, galactose, butanoate, and pentose phosphate and glycolysis/gluconeogenesis were for the majority associated to obese, while biosynthesis and metabolism of glycan, biosynthesis of secondary bile acid, metabolism of steroid hormone and lipoic acid were associated to NW adolescents. Our study revealed unique features of gut microbiota in terms of ecological patterns, microbial composition and metabolism in obese patients. The assignment of novel obesity bacterial markers may open avenues for the development of patient-tailored treatments dependent on age-related microbiota profiles.