INTESTINAL RESECTION INDUCES CHANGES IN MICROBIOTA COMPOSITION AND FUNCTION: IMPACT ON THE HOST-MICROBIOTA CROSSTALK

Background: Short bowel syndrome (SBS) represents the most common cause of intestinal failure following massive intestinal resection.After intestinal loss, the remnant bowel undergoes multifactorial compensatory processes termed adaptation.Previous studies have demonstrated the impact of intestinal resection on microbiota composition in the early stage of intestinal adaptation.However, little is known about microbial metabolism after resection.Aim: We aimed to investigate the microbial composition and metabolism alterations following intestinal resection on host-microbiota crosstalk in early and long-term adaptation.Methods: Male C57BL6 mice were subjected to an ileocecal resection (ICR) or a transection (sham).Physiological parameters and intestinal adaptation were analyzed during a time course including a pre-operative time point (pre-op) and at day 3 and week 1, 2, 3 and 8 following surgery.Microbial composition and function analysis were performed using 16S rRNA gene sequencing and PICRUSt metagenomic inference coupled with metabolomics using nuclear magnetic resonance spectroscopy in fecal samples.Results: Features of intestinal adaptation including taller villi (p=0.0001),deeper crypts (p=0.0006),increased intestinal length (p<0.0001) were confirmed in ICR.Microbiota diversity estimated by the number of observed taxa and the Shannon index were significantly reduced in ICR compared to pre-op and sham (p<0.001).In addition, drastic microbial community changes, characterized by a decrease in Bacteroidetes and an increase in Firmicutes and Actinobacteria, occurred in ICR after a week and were sustained overtime compared to sham.Interestingly, changes in fecal microbial composition were associated with alterations in microbial metabolism.As a consequence, microbial-derived short-chain fatty acids, were significantly reduced after a week and remained lower in ICR compared to sham and pre-op.In contrast, ICR mice exhibited higher lactate concentrations after 2 weeks and onward (p=0.0002).Fecal metabolome included important alterations in protein metabolism with a significant increase in branched-chain amino acids (AA) and aromatic AA correlated with altered inferred microbial AA metabolism gene.During the adaptation process, we also observed a significantly lower body weight gain in ICR compared to sham associated with changes in body composition.Early adaptive responses in ICR mice were correlated with early reductions in fat mass and increases in lean mass after 1, 2 and 3 weeks post-surgery.Conclusion: This study supports the hypothesis that ICR not only affects microbiota composition but also microbial metabolism which can consequently affects the host metabolism.Further integrative analysis will provide new insight to understanding altered host-microbiota interactions in the adaptive responses following intestinal resection.