Gut microbial diversity is reduced and is associated with colonic inflammation in a piglet model of short bowel syndrome

Abstract

IntroductionShort bowel syndrome (SBS) is the clinical state of malabsorption and malnutrition that occurs following small bowel resection (SBR). 1 Surgical resection of the small bowel may be required for the treatment of a range of conditions including congenital bowel abnormalities and necrotising enterocolitis in children and Crohn disease, trauma and malignancy in adults. Although the underlying reason for SBR between adults and children may differ, the clinical manifestations and consequences of SBS are similar. The symptoms of SBS reflect the loss of absorptive surface area and functional disturbance of the Background and objectives: Following small bowel resection (sBR), the luminal environment is altered, which contributes to clinical manifestations of short bowel syndrome (sBs) including malabsorption, mucosal inflammation and bacterial overgrowth. however, the impact of sBR on the colon has not been well-defined. The aims of this study were to characterize the colonic microbiota following sBR and to assess the impact of sBR on mucosal inflammation in the colon.Results: analysis of the colonic microbiota demonstrated that there was a significant level of dysbiosis both two and six weeks post-sBR, particularly in the phylum Firmicutes, coupled with a decrease in overall bacterial diversity in the colon. This decrease in diversity was associated with an increase in colonic inflammation six weeks post-surgery.Methods: Female (4-week old) piglets (5-6/group) received a 75% sBR, a transection (sham) or no surgery. compositional analysis of the colonic microbiota was performed by high-throughput sequencing, two-and six-weeks post-surgery. The gene expression of the pro-inflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, IL-18 and tumor necrosis factor (TNF)-α in the colonic mucosa was assessed by qRT-pcR and the number of macrophages and percentage inducible nitric oxide synthase (iNOs) staining in the colonic epithelium were quantified by immunohistochemistry.Conclusions: sBR significantly decreased the diversity of the colonic microbiota and this was associated with an increase in colonic mucosal inflammation. This study supports the hypothesis that sBR has a significant impact on the colon and that this may play an important role in defining clinical outcome.

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

“…Surprisingly, we did not find differences in the overall bacterial diversity throughout the GI tract as a result of bowel resection. Recent studies of both porcine model small bowel resection 12 and murine ileocecal resection 18 displayed decreased phylogenetic diversity in the resected area compared to sham-operated animals. However, unlike these studies, we did not use pre-operative antibiotics.…”

“…Antibiotics have been shown to exert profound effects on the gut microbiome 19 and predominantly diminish diversity. 20 Furthermore, in the porcine study, 12 75 % of the small bowel was resected, whereas we removed only 50 %. Because the mice in our study gained weight after a period of intestinal adaptation, it is likely that our model retains sufficient intestinal length to avoid dysbiosis.…”

“…Additionally, a previous study using a porcine model showed only very small differences in the microbiota between sham and non-operated pigs. 12 …”

Why Are Omics Technologies Important to Understanding the Role of Nutrition in Inflammatory Bowel Diseases?

“…A reduction in the diversity of the intestinal microbiota has been associated with intestinal inflammation in animal studies, including mice [86] and pigs [87], and in human studies [88] and, therefore, the maintenance of diversity represents a plausible mechanism by which curcumin may exert its effect. Systems biology approaches on IBD have usefully begun to focus on gut microbial metabolism [89].…”

Mechanisms of intestinal adaptation

“…This topic has been reviewed recently [70]. The role of the microbiome is also being explored experimentally in mouse [71] and piglet [72] models of short bowel syndrome.…”