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

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 ).

Figures

Fig. 1

Metabolic and microbial diversity improvements during a 1-year period after RYGB. Box plots represent features measured at the three different time points. Lines connect the measures from the same subject. For each pairwise comparison between time points, the P value of the Wilcoxon signed-rank test (P), the difference between the medians (Δ), and difference between medians normalized by time difference (Δ′) are denoted. a Host metabolism improvements. Postprandial glucose and GLP-1 levels were calculated as area under the curve during a standardized meal test. b Microbial species diversity improvements

Fig. 2

Gut microbial community differences induced by RYGB. Principal component analysis based on log transformed mOTU species abundances shows a clear separation between pre-RYGB and post-RYGB fecal samples. The variation explained by each component is shown on its axis. MO months, Y year

Fig. 3

Changes in individual gut microbial species following RYGB. Median fold changes in relative abundances of 31 mOTU species that changed between baseline and 3 months (3MO, bottom panel), and 16 among these that changed between baseline and 1 year (1Y, top panel) after RYGB. For each bacterial species, the cloud of circles represents all fold changes calculated when excluding one other species from the abundance table. The horizontal grey lines at −1 and 1 mark when the microbes halved or doubled their relative abundance. Exclusion of Prevotella copri substantially altered the fold change for many species and the corresponding fold change is denoted as an empty triangle. The colored band in each panel shows the statistical significance of Wilcoxon signed-rank tests after our compositionality test. Asterisks mark species that have already been reported in previous studies

Fig. 4

Microbial functional changes following RYGB. Box plots represent fold changes (log2) in the 53 KEGG modules that increased in relative abundance between baseline and 3 months (3MO, left panel) and 44 among these that increased between baseline and 1 year (1Y, right panel) after RYGB. The different KEGG functional categories are represented by different colors and grouped together when possible with corresponding labels at the right side of the plot. PTS phosphotransferase systems, GABA gamma-aminobutyric acid

Fig. 5

A model of gut microbial changes following RYGB. Blue boxes show inferred changes in microbial features (functional potential or taxonomic), while green boxes show the effects induced by RYGB either in the gut or in the host metabolism. Black boxes indicate hypotheses based on our data or other studies. Arrows connect shifts that are related. Since we did not measure inflammation markers we do not report an increase or decrease in inflammation, but we connect it to an observed change based on existing literature. All features shown here exhibited changes 3 months after RYGB and most maintained the changes up to 1 year after RYGB. Asterisks denote features that did not maintain the changes 1 year after RYGB