Alterations of Gut Microbiota After Biliopancreatic Diversion with Duodenal Switch in Wistar Rats

Paulette Mukorako, Carlos Lopez, Elena-Dana Baraboi, Marie-Claude Roy, Julie Plamondon, Natacha Lemoine, Laurent Biertho, Thibault V. Varin, André Marette, Denis Richard

The biliopancreatic diversion with duodenal switch (BPD/DS) represents the most effective surgical procedure for the treatment of severe obesity and associated type 2 diabetes. The mechanisms whereby BPD/DS exerts its positive metabolic effects have however yet to be fully delineated. The objective of this study was to distinguish the effects of the two components of BPD/DS, namely the sleeve gastrectomy (SG) and the DS derivation, on gut microbiota, and to appraise whether changes in microbial composition are linked with surgery-induced metabolic benefits. BPD/DS, DS, and SG were performed in Wistar rats fed a standard chow diet. Body weight and energy intake were measured daily during 8 weeks post-surgery, at which time glucagon-like peptide 1 (GLP-1), peptide tyrosine tyrosine (PYY), insulin, and glucose were measured. Fecal samples were collected prior to surgery and at 2 and 8 weeks post-surgery. Intraluminal contents of the alimentary, biliopancreatic, and common limbs (resulting from BPD/DS) were taken from the proximal portion of each limb. Fecal and small intestinal limb samples were analyzed by 16S ribosomal RNA gene sequencing. BPD/DS and DS led to lower digestible energy intake (P = 0.0007 and P = 0.0002, respectively), reduced weight gain (P < 0.0001) and body fat mass (P < 0.0001), improved glucose metabolism, and increased GLP-1 (P = 0.0437, SHAM versus DS) and PYY levels (P < 0.0001). These effects were associated with major alterations of both the fecal and small intestinal microbiota, as revealed by significant decrease in bacterial richness and diversity at 2 (P < 0.0001, Chao1 index; P < 0.0001, Shannon index) and 8 weeks (P = 0.0159, SHAM versus DS, Chao1 index; P = 0.0219, SHAM versus DS, P = 0.0472, SHAM versus BPD/DS, Shannon index) post-surgery in BPD/DS and DS, and increased proportions of Bifidobacteriales (a 60% increase in both groups) but reduced Clostridiales (a 50% decrease and a 90% decrease respectively), which were mostly accounted at the genus level by higher relative abundance of Bifidobacterium in both the fecal and intestinal limb samples, as well as reduced abundance of Peptostreptococcaceae and Clostridiaceae in the small intestine. Those effects were not seen in SG rats. The metabolic benefits following BPD/DS are seemingly due to the DS component of the surgery. Furthermore, BPD/DS causes marked alterations in fecal and small intestinal microbiota resulting in reduced bacterial diversity and richness. Our data further suggest that increased abundance of Bifidobacterium and reduced level of two Clostridiales species in the gut microbiota might contribute to the positive metabolic outcomes of BPD/DS.