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



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.



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.



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.



Current controlled trials (ID NCT00810823 , NCT01579981 , and NCT01993511 ).
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
Albert
A
Palleja
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.|Danish Diabetes Academy, 5000, Odense, Denmark.
Alireza
A
Kashani
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
Kristine H
KH
Allin
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
Trine
T
Nielsen
BGI-Shenzhen, Shenzhen, 518083, China.
Chenchen
C
Zhang
BGI-Shenzhen, Shenzhen, 518083, China.
Yin
Y
Li
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
Thorsten
T
Brach
BGI-Shenzhen, Shenzhen, 518083, China.
Suisha
S
Liang
BGI-Shenzhen, Shenzhen, 518083, China.
Qiang
Q
Feng
Department of Endocrinology, Hvidovre Hospital, 2650, Hvidovre, Denmark.
Nils Bruun
NB
Jørgensen
Department of Endocrinology, Hvidovre Hospital, 2650, Hvidovre, Denmark.
Kirstine N
KN
Bojsen-Møller
Department of Endocrinology, Hvidovre Hospital, 2650, Hvidovre, Denmark.
Carsten
C
Dirksen
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
Kristoffer S
KS
Burgdorf
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.|Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, 2200, Copenhagen, Denmark.
Jens J
JJ
Holst
Department of Endocrinology, Hvidovre Hospital, 2650, Hvidovre, Denmark.
Sten
S
Madsbad
BGI-Shenzhen, Shenzhen, 518083, China.|iCarbonX, Shenzhen, 518083, China.|Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 10083, China.|Department of Biology, University of Copenhagen, 2200, Copenhagen, Denmark.
Jun
J
Wang
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark. oluf@sund.ku.dk.
Oluf
O
Pedersen
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark. torben.hansen@sund.ku.dk.|Faculty of Health Sciences, University of Southern Denmark, 5000, Odense, Denmark. torben.hansen@sund.ku.dk.
Torben
T
Hansen
The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200, Copenhagen, Denmark. arumugam@sund.ku.dk.
Manimozhiyan
M
Arumugam
D000713:Anastomosis, Roux-en-Y; D001419:Bacteria / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D044822:Biodiversity; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D056186:Metagenomics; D009767:Obesity, Morbid / Q000382:microbiology* / Q000601:surgery*; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D015431:Weight Loss