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Journal ArticleDOI

Differential Changes in Gut Microbiota After Gastric Bypass and Sleeve Gastrectomy Bariatric Surgery Vary According to Diabetes Remission

01 Apr 2017-Obesity Surgery (Springer US)-Vol. 27, Iss: 4, pp 917-925
TL;DR: Overall, RYGB produces greater and more predicted favourable changes in gut microbiota functional capacity than SG, and is likely to be associated with remission of type 2 diabetes after distinct types of bariatric surgery.
Abstract: It is unclear whether specific gut microbiota is associated with remission of type 2 diabetes (T2D) after distinct types of bariatric surgery. The aim of this study is to examine gut microbiota changes after laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery in obese patients with T2D. Whole-metagenome shotgun sequencing of DNA fragments using Illumina HiSeq2000 was obtained from stool samples collected from 14 obese T2D patients pre-operatively (while on very low calorie diet) and 1 year after randomisation to laparoscopic SG (n = 7) or RYGB (n = 7). Resulting shotgun reads were annotated with Kyoto Encyclopedia of Genes and Genomes (KEGG). Body weight reduction and dietary change was similar 1 year after both surgery types. Identical proportions (n = 5/7) achieved diabetes remission (HbA1c < 48 mmol/mol without medications) 1 year after RYGB and SG. RYGB resulted in increased Firmicutes and Actinobacteria phyla but decreased Bacteroidetes phyla. SG resulted in increased Bacteroidetes phyla. Only an increase in Roseburia species was observed among those achieving diabetes remission, common to both surgery types. KEGG Orthology and pathway analysis predicted contrasting and greater gut microbiota metabolism changes after diabetes remission following RYGB than after SG. Those with persistent diabetes post-operatively had higher Desulfovibrio species pre-operatively. Overall, RYGB produces greater and more predicted favourable changes in gut microbiota functional capacity than SG. An increase in Roseburia species was the only compositional change common to both types of surgery among those achieving diabetes remission.
Citations
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Journal ArticleDOI
TL;DR: Evidence from 42 human studies reporting microbial associations with disease, and supporting preclinical studies or clinical trials using treatments with probiotics are identified, found the genera of Bifidobacterium, Bacteroides, Faecalibacteriaium, Akkermansia and Roseburia were negatively associated with T2D, while theGenera of Ruminococcus, Fusobacteria, and Blautia were positively associated withT2D.

762 citations


Cites background from "Differential Changes in Gut Microbi..."

  • ...Finally, it was also shown that another species of this genus, Faecalibacterium cf, was associated with remission of diabetes after bariatric surgery [11]....

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  • ...Accordingly, in investigations that analyzed this genus on the species level, Bacteroides intestinalis, Bacteroides 20 3 and Bacteroides vulgatus were decreased in T2D patients and Bacteroides stercoris were enriched after sleeve gastrectomy (SG) surgery in T2D patients with diabetes remission [5,11,17,24]....

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  • ...dentium and disease in patients treated with metformin or after undergoing gastric bypass surgery [6,11]....

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  • ...Accordingly, investigations that were able to assign Roseburia to a species level also reported a negative association with disease for Roseburia inulinivorans, Roseburia_272, and one unclassified OTU from this genus [11,17,24]....

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  • ...SR1/5 enriched by metformin treatment [6], another found Ruminococcus bromii enriched and Ruminococcus torques decreased after bariatric surgery and diabetes remission [11]....

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Journal ArticleDOI
TL;DR: While the field of gut microbiome and its role in obesity is early in its stage of development, it holds a promising future in providing us with novel therapeutic targets that may restore the gut microbiome to a healthy state and help in the prevention and treatment of obesity.
Abstract: Obesity is a complex metabolic disease caused, in part, by the interaction between an individual's genetics, metabolism, and environment. Emerging evidence supports the role of gut microbiota in mediating the interaction between the host and environment by extracting energy from food otherwise indigestible by the host and producing metabolites and cytokines that affect host metabolism. Furthermore, gut microbial imbalance or dysbiosis has been shown in metabolic diseases including obesity, and recent studies are beginning to unravel the mechanisms involved. The gut microbiota affects host metabolism and obesity through several pathways involving gut barrier integrity, production of metabolites affecting satiety and insulin resistance, epigenetic factors, and metabolism of bile acids and subsequent changes in metabolic signaling. While the field of gut microbiome and its role in obesity is early in its stage of development, it holds a promising future in providing us with novel therapeutic targets that may restore the gut microbiome to a healthy state and help in the prevention and treatment of obesity.

164 citations

Journal ArticleDOI
TL;DR: Results show that restrictive diets and bariatric surgery reduce microbial abundance and promote changes in microbial composition that could have long‐term detrimental effects on the colon, in contrast, prebiotics might restore a healthy microbiome and reduce body fat.
Abstract: Imbalances in the gut microbiota, the bacteria that inhabit the intestines, are central to the pathogenesis of obesity This systematic review assesses the association between the gut microbiota and weight loss in overweight/obese adults and its potential manipulation as a target for treating obesity This review identified 43 studies using the keywords 'overweight' or 'obesity' and 'microbiota' and related terms; among these studies, 17 used dietary interventions, 11 used bariatric surgery and 15 used microbiota manipulation The studies differed in their methodologies as well as their intervention lengths Restrictive diets decreased the microbiota abundance, correlated with nutrient deficiency rather than weight loss and generally reduced the butyrate producers Firmicutes, Lactobacillus sp and Bifidobacterium sp The impact of surgical intervention depended on the given technique and showed a similar effect on butyrate producers, in addition to increasing the presence of the Proteobacteria phylum, which is related to changes in the intestinal absorptive surface, pH and digestion time Probiotics differed in strain and duration with diverse effects on the microbiota, and they tended to reduce body fat Prebiotics had a bifidogenic effect and increased butyrate producers, likely due to cross-feeding interactions, contributing to the gut barrier and improving metabolic outcomes All of the interventions under consideration had impacts on the gut microbiota, although they did not always correlate with weight loss These results show that restrictive diets and bariatric surgery reduce microbial abundance and promote changes in microbial composition that could have long-term detrimental effects on the colon In contrast, prebiotics might restore a healthy microbiome and reduce body fat

143 citations


Cites background or methods from "Differential Changes in Gut Microbi..."

  • ...Two studies compared different surgical interventions for weight loss (44,48)....

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  • ...Inflammatory markers were positively correlated with Propionibacterium (44) and negatively correlated with F. prausnitzii (38)....

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  • ...Inflammatory markers were positively correlated with Propionibacterium (44) and negatively correlated with F....

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  • ...Abbreviations: BF, body fat; BIB, bilio-intestinal bypass; BMI, body mass index; BP, blood pressure; BW, body weight; CRC, colorectal cancer; DBP, diastolic blood pressure; DGGE, denaturing gradient gel electrophoresis; F/B ratio, Firmicutes to Bacteroidetes ratio; FBG, fasting blood glucose; FBI, fasting blood insulin; FISH, fluorescence in situ hybridization; GB, gastric banding; LSG, laparoscopic sleeve gastrectomy; NRCT, non-randomized clinical trial; qPCR, quantitative polymerase chain reaction; RCT, randomized clinical Trial; RoB, risk of bias [Cochrane Collaboration’s tool]; RoBANS, risk of bias assessment tool for nonrandomized studies; RYGB, Roux-en-Y gastric bypass; SBP, systolic blood pressure; SCFA, short-chain fatty acids; SD, standard deviation; TC, total cholesterol; TG, triglycerides; T2DM, type 2 diabetes mellitus; VBG, vertical banded gastroplasty; WC, waist circumference....

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  • ...Damms-Machado et al. (41) reported that LSG promoted more profound changes in the gut microbiota composition than a very-low-calorie diet, despite producing similar weight loss....

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Journal ArticleDOI
TL;DR: There is strong evidence to support a considerable alteration of the gut microbiome after bariatric surgery and the mechanisms that link the gut microbiota and metabolic alterations in human metabolism.
Abstract: Objective Bariatric surgery is recommended for patients with obesity and type 2 diabetes. Recent evidence suggested a strong connection between gut microbiota and bariatric surgery. Design Systematic review. Methods The PubMed and OVID EMBASE were used, and articles concerning bariatric surgery and gut microbiota were screened. The main outcome measures were alterations of gut microbiota after bariatric surgery and correlations between gut microbiota and host metabolism. We applied the system of evidence level to evaluate the alteration of microbiota. Modulation of short-chain fatty acid and gut genetic content was also investigated. Results Totally 12 animal experiments and 9 clinical studies were included. Based on strong evidence, 4 phyla (Bacteroidetes, Fusobacteria, Verrucomicrobia and Proteobacteria) increased after surgery; within the phylum Firmicutes, Lactobacillales and Enterococcus increased; and within the phylum Proteobacteria, Gammaproteobacteria, Enterobacteriales Enterobacteriaceae and several genera and species increased. Decreased microbial groups were Firmicutes, Clostridiales, Clostridiaceae, Blautia and Dorea. However, the change in microbial diversity is still under debate. Faecalibacterium prausnitzii, Lactobacillus and Coprococcus comes are implicated in many of the outcomes, including body composition and glucose homeostasis. Conclusions There is strong evidence to support a considerable alteration of the gut microbiome after bariatric surgery. Deeper investigations are required to confirm the mechanisms that link the gut microbiome and metabolic alterations in human metabolism.

142 citations

Journal ArticleDOI
TL;DR: The metabolic benefits of gastric bypass surgery and diet were similar and were apparently related to weight loss itself, with no evident clinically important effects independent of weight loss.
Abstract: Background Some studies have suggested that in people with type 2 diabetes, Roux-en-Y gastric bypass has therapeutic effects on metabolic function that are independent of weight loss. Meth...

137 citations

References
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Journal ArticleDOI
TL;DR: The command-line tool cutadapt is developed, which supports 454, Illumina and SOLiD (color space) data, offers two adapter trimming algorithms, and has other useful features.
Abstract: When small RNA is sequenced on current sequencing machines, the resulting reads are usually longer than the RNA and therefore contain parts of the 3' adapter. That adapter must be found and removed error-tolerantly from each read before read mapping. Previous solutions are either hard to use or do not offer required features, in particular support for color space data. As an easy to use alternative, we developed the command-line tool cutadapt, which supports 454, Illumina and SOLiD (color space) data, offers two adapter trimming algorithms, and has other useful features. Cutadapt, including its MIT-licensed source code, is available for download at http://code.google.com/p/cutadapt/

20,255 citations


"Differential Changes in Gut Microbi..." refers methods in this paper

  • ...All reads were quality trimmed using Cutadapt (minimum Phred score 20, minimum read length 50 bp) [20]....

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Journal ArticleDOI
TL;DR: UCLUST is a new clustering method that exploits USEARCH to assign sequences to clusters and offers several advantages over the widely used program CD-HIT, including higher speed, lower memory use, improved sensitivity, clustering at lower identities and classification of much larger datasets.
Abstract: Motivation: Biological sequence data is accumulating rapidly, motivating the development of improved high-throughput methods for sequence classification. Results: UBLAST and USEARCH are new algorithms enabling sensitive local and global search of large sequence databases at exceptionally high speeds. They are often orders of magnitude faster than BLAST in practical applications, though sensitivity to distant protein relationships is lower. UCLUST is a new clustering method that exploits USEARCH to assign sequences to clusters. UCLUST offers several advantages over the widely used program CD-HIT, including higher speed, lower memory use, improved sensitivity, clustering at lower identities and classification of much larger datasets. Availability: Binaries are available at no charge for non-commercial use at http://www.drive5.com/usearch Contact: [email protected] Supplementary information:Supplementary data are available at Bioinformatics online.

17,301 citations


"Differential Changes in Gut Microbi..." refers background or methods in this paper

  • ...Microbiota functional profiles were identified using USEARCH [21] and HUMANn (v99b) against Kyoto Encyclopedia of Genes and Genomes (KEGG) database (v44) [22], to obtain relative gene abundance and KEGG pathways which were differentially abundant among samples from SG vs RYGB or those with diabetes remission vs non-remission groups....

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  • ...Microbiota functional profiles were identified using USEARCH [21] and HUMANn (v99b) against Kyoto Encyclopedia of Genes and Genomes (KEGG) database (v44) [22], to obtain relative gene abundance and KEGG pathways which were differentially abundant among samples from SG vs RYGB or those with diabetes remission vs non-remission groups....

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  • ...0 [21] and reported as relative abundance in each sample....

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Journal ArticleDOI
21 Dec 2006-Nature
TL;DR: It is demonstrated through metagenomic and biochemical analyses that changes in the relative abundance of the Bacteroidetes and Firmicutes affect the metabolic potential of the mouse gut microbiota and indicates that the obese microbiome has an increased capacity to harvest energy from the diet.
Abstract: The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.

10,126 citations

Journal ArticleDOI
TL;DR: A new method for metagenomic biomarker discovery is described and validates by way of class comparison, tests of biological consistency and effect size estimation to address the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities.
Abstract: This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.

9,057 citations


"Differential Changes in Gut Microbi..." refers methods in this paper

  • ...Statistical Analysis Statistically significant differences were analysed using software LefSe [23]....

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  • ...Linear discriminant analysis (LDA) effect size (LefSe) was used to identify significant differences in relative abundances of gut microbiota phyla, genera and species between pre- and post-operative samples at 1 year after RYGB or SG....

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Journal ArticleDOI
22 Jan 2009-Nature
TL;DR: The faecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers are characterized to address how host genotype, environmental exposure and host adiposity influence the gut microbiome.
Abstract: The human distal gut harbours a vast ensemble of microbes (the microbiota) that provide important metabolic capabilities, including the ability to extract energy from otherwise indigestible dietary polysaccharides. Studies of a few unrelated, healthy adults have revealed substantial diversity in their gut communities, as measured by sequencing 16S rRNA genes, yet how this diversity relates to function and to the rest of the genes in the collective genomes of the microbiota (the gut microbiome) remains obscure. Studies of lean and obese mice suggest that the gut microbiota affects energy balance by influencing the efficiency of calorie harvest from the diet, and how this harvested energy is used and stored. Here we characterize the faecal microbial communities of adult female monozygotic and dizygotic twin pairs concordant for leanness or obesity, and their mothers, to address how host genotype, environmental exposure and host adiposity influence the gut microbiome. Analysis of 154 individuals yielded 9,920 near full-length and 1,937,461 partial bacterial 16S rRNA sequences, plus 2.14 gigabases from their microbiomes. The results reveal that the human gut microbiome is shared among family members, but that each person's gut microbial community varies in the specific bacterial lineages present, with a comparable degree of co-variation between adult monozygotic and dizygotic twin pairs. However, there was a wide array of shared microbial genes among sampled individuals, comprising an extensive, identifiable 'core microbiome' at the gene, rather than at the organismal lineage, level. Obesity is associated with phylum-level changes in the microbiota, reduced bacterial diversity and altered representation of bacterial genes and metabolic pathways. These results demonstrate that a diversity of organismal assemblages can nonetheless yield a core microbiome at a functional level, and that deviations from this core are associated with different physiological states (obese compared with lean).

6,970 citations

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