Roux-en-Y gastric bypass surgery of morbidly obese patients induces swift and persistent changes of the individual gut microbiota

Albert Pallejá(Novo Nordisk Foundation), Alireza Kashani(University of Copenhagen), Kristine H. Allin(University of Copenhagen), Trine Nielsen(University of Copenhagen), Chenchen Zhang(BGI Group (China)), Yin Li(BGI Group (China)), Thorsten Brach(University of Copenhagen), Suisha Liang(BGI Group (China)), Qiang Feng(BGI Group (China)), Nils B. Jørgensen(Hvidovre Hospital), Kirstine N. Bojsen‐Møller(Hvidovre Hospital), Carsten Dirksen(Hvidovre Hospital), Kristoffer Sølvsten Burgdorf(University of Copenhagen), Jens J. Holst(Novo Nordisk Foundation), Sten Madsbad(Hvidovre Hospital), Jun Wang(China Agricultural University), Oluf Pedersen(University of Copenhagen), Torben Hansen(University of Southern Denmark), Manimozhiyan Arumugam(University of Copenhagen)
Genome Medicine
June 15, 2016
Cited by 312Open Access
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Abstract

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is an effective means to achieve sustained weight loss for morbidly obese individuals. Besides rapid weight reduction, patients achieve major improvements of insulin sensitivity and glucose homeostasis. Dysbiosis of gut microbiota has been associated with obesity and some of its co-morbidities, like type 2 diabetes, and major changes of gut microbial communities have been hypothesized to mediate part of the beneficial metabolic effects observed after RYGB. Here we describe changes in gut microbial taxonomic composition and functional potential following RYGB. METHODS: We recruited 13 morbidly obese patients who underwent RYGB, carefully phenotyped them, and had their gut microbiomes quantified before (n = 13) and 3 months (n = 12) and 12 months (n = 8) after RYGB. Following shotgun metagenomic sequencing of the fecal microbial DNA purified from stools, we characterized the gut microbial composition at species and gene levels followed by functional annotation. RESULTS: In parallel with the weight loss and metabolic improvements, gut microbial diversity increased within the first 3 months after RYGB and remained high 1 year later. RYGB led to altered relative abundances of 31 species (P < 0.05, q < 0.15) within the first 3 months, including those of Escherichia coli, Klebsiella pneumoniae, Veillonella spp., Streptococcus spp., Alistipes spp., and Akkermansia muciniphila. Sixteen of these species maintained their altered relative abundances during the following 9 months. Interestingly, Faecalibacterium prausnitzii was the only species that decreased in relative abundance. Fifty-three microbial functional modules increased their relative abundance between baseline and 3 months (P < 0.05, q < 0.17). These functional changes included increased potential (i) to assimilate multiple energy sources using transporters and phosphotransferase systems, (ii) to use aerobic respiration, (iii) to shift from protein degradation to putrefaction, and (iv) to use amino acids and fatty acids as energy sources. CONCLUSIONS: Within 3 months after morbidly obese individuals had undergone RYGB, their gut microbiota featured an increased diversity, an altered composition, an increased potential for oxygen tolerance, and an increased potential for microbial utilization of macro- and micro-nutrients. These changes were maintained for the first year post-RYGB. TRIAL REGISTRATION: Current controlled trials (ID NCT00810823 , NCT01579981 , and NCT01993511 ).


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