Small Bowel Resection Induces Long-Term Changes in the Enteric Microbiota of Mice

Abstract

Purpose The enteric microbiome is known to play a major role in healthy gut homeostasis and several disease states. It may also contribute to both the intestinal recovery and complications that occur in patients with short bowel syndrome. The extent and nature of alterations to the gut microbiota following intestinal resection, however, are not well studied in a controlled setting. The purpose of this investigation is to characterize the effects of massive small bowel resection on the murine enteric microflora. Methods Wild-type C57BL6 mice, following a week of acclamation to a liquid rodent diet, underwent either 50 % proximal small bowel resection (SBR) or a sham operation. Mice were sacrificed, and enteric contents from the small bowel, cecum, and stool were harvested at 7 and 90 days post-operatively. DNA was isolated, and the V3–V5 regions of the 16s rRNA gene amplified and pyrosequenced on a Roche 454 platform. Sequences were clustered into operation taxonomic units and classified. Communities were then analyzed for diversity and phylogenic composition. Results In the long-term group, the microbes inhabiting the ileum of mice undergoing SBR and sham operation differed significantly at the genus level (p<0.001). Small bowel contents collected before and after SBR also differed significantly (p= 0.006). This was driven by an increase in Lactobacillus and decrease in Enterobacteriaceae species in mice undergoing SBR. No difference was seen in the long-term stool or in stool, cecal, or ileal contents in the short-term. No difference in microbial community diversity was found in any group. Conclusion Bowel resection induces long-term changes in the microbial community of the murine ileum, but not at more distal sites of the gastrointestinal tract. The increase in Lactobacillus encountered small bowel of resected mice correlates with limited previous studies. These changes may reflect an adaptive response of the microbiota to maximize energy extraction, but further studies are needed to establish the role played by this altered community.

Liver steatosis induced by small bowel resection is prevented by oral vancomycin

“…This contrasts with an earlier study in which we revealed significant alterations in the microbiota of the small bowel, but not in the feces after SBR 9 . The variations between current and prior studies might be due to altered time of fecal collection (7 and 90 days versus 21 days), small bowel lumen versus passed stool, or different housing conditions from one time of year to another.…”

“…7 Increased abundance of Firmicutes (primarily Gram-positive bacteria) is one of the more prevalent findings involving an obese phenotype 8 . Similar to obesity, we have identified a remarkably similar pattern of increased Firmicutes abundance in the small intestine after SBR 9 . Using our murine SBR model, we have established that mice exhibit a unique body composition profile in which fat is preferentially replaced over lean muscle during recovery.…”

Toll-like receptor 4 is critical for the development of resection-associated hepatic steatosis

“…Vancomycin is not absorbed from the gastrointestinal tract and kills Gram-positive bacteria, which have been described to bloom in the gut of mice after SBR(35) and patients(21, 36) with short gut syndrome. Taken together, the observations of our past and present studies would endorse critical roles for both Gram-negative and positive organisms working synergistically to promote resection-associated steatosis.…”

The role of intestinal bacteria in the development and progression of gastrointestinal tract neoplasms

“…In a mouse model of small bowel resection, changes in the ileal microbial community were observed up to 90 days after surgery [157]. The intestinal microbiota may influence anastomotic leak after gastrointestinal surgery.…”