Distinct patterns in the gut microbiota after surgical or medical therapy in obese patients

Abstract

Bariatric surgery is highly successful in improving health compared to conventional dietary treatments. It has been suggested that the gut microbiota is a relevant factor in weight loss after bariatric surgery. Considering that bariatric procedures cause different rearrangements of the digestive tract, they probably have different effects on the gut microbiota. In this study, we compared the impact of medical treatment, sleeve gastrectomy and Roux-en-Y gastric bypass on the gut microbiota from obese subjects. Anthropometric and clinical parameters were registered before, 6 and 12 months after treatment. Fecal samples were collected and microbiota composition was studied before and six months post treatment using 16S rRNA gene sequencing and qPCR. In comparison to dietary treatment, changes in intestinal microbiota were more pronounced in patients subjected to surgery, observing a bloom in Proteobacteria. Interestingly, Bacteroidetes abundance was largely different after six months of each surgical procedure. Furthermore, changes in weight and BMI, or glucose metabolism, correlated positively with changes in these two phyla in these surgical procedures. These results indicate that distinct surgical procedures alter the gut microbiota differently, and changes in gut microbiota might contribute to health improvement. This study contributes to our understanding of the impact of weight loss surgery on the gut microbiota, and could be used to replicate this effect using targeted therapies.

Keywords: Bariatric surgery; Gastric bypass; Human gut microbiota; Sleeve gastrectomy.

Figure 1. Rarefaction curves and Principal Component Analysis of the gut microbiota composition of the subjects of the study, obtained by 16S rRNA sequencing and QIIME.

(A) rarefaction curves for all samples sequenced, indicating the number of OTUs observed with different sequencing depths; (B–D) 2D-PCoA analysis of gut microbiota composition at time 0 (red squares) compared to 6 months after treatment (blue circles), for medical treatment subjects (MT), Sleeve Gastrectomy (SG) and Roux-en-Y Gastric Bypass (RYGB) groups.

Figure 2. Relative abundance of major bacterial phyla in the gut microbiota of the three groups of the study, before and after each treatment.

(A) average relative abundance of four representative phyla (indicated in the upper part), at time 0 and 6 months, in medical treatment (MT), Sleeve Gastrectomy (SG) or Roux-en-Y Gastric Bypass (RYGB) groups; (B–D) changes in the abundance of each phylum after/before each treatment. The phyla are represented from left to right side as Act (Actinobacteria), Bac (Bacteroidetes), Fir (Firmicutes), Pro (Proteobacteria). Values were expressed as fold change and log(2) normalized; E: Bacteroidetes/Firmicutes ratio at time 0 (red) and 6 months after treatment (light blue) for Medical Treatment (MT), Roux-en-Y gastric bypass (GB) and Sleeve Gastrectomy (SG). Asterisk indicates significant fold change differences (p-value < 0,05).

Figure 3. Changes in major phyla in the gut microbiota after each obesity treatment measured by qPCR.

(A–C) ratio of the abundance of each phylum after/before each treatment for Medical Treatment (A), Roux-en-Y gastric bypass (B) and Sleeve Gastrectomy (C). The changes are represented from left to right side as Act (Actinobacteria), Bac (Bacteroidetes), Fir (Firmicutes), Ent (Enterobacteriales). Values were expressed as fold change and log₂ normalized. (D) Ratio of Bacteroidetes/Firmicutes at time 0 (black) and six months after treatment (grey). Asterisk indicates significant fold change differences (p-value < 0.05).

Figure 4. Gut microbiota comparison across subjects before and after the obesity treatment.

Heatmap of pairwise Spearman Rank correlations for gut microbiota abundance, with other subjects in the study. (A) Pairwise correlations for all subjects before each intervention (Medical Treatment (MT), Roux-en-Y Gastric Bypass (GB) and Sleeve Gastrectomy (SG); numbers indicate subjects); (B) Pairwise correlations for all subjects six months after each treatment. The legend in the bottom indicates the scale of correlation across different gut microbiota compositions.

Figure 5. Correlations between clinical data change and gut microbiota variation.

Heatmap of pairwise Spearman Rank correlation analysis of microbiome changes with changes in clinical markers, considering data after and before the treatment. Data corresponds to subjects on Medical Treatment (A), Roux-en-Y gastric bypass (B) and Sleeve Gastrectomy (C). The phyla are represented from left to right side as Act (Actinobacteria), Fir (Firmicutes), Bac (Bacteroidetes) and Pro (Proteobacteria). Blue denotes a negative correlation while yellow indicates positive correlations. The asterisk denotes significant correlation values (p-value < 0.05).