Multiphasic analysis of the temporal development of the distal gut microbiota in patients following ileal pouch anal anastomosis

Abstract

BackgroundThe indigenous gut microbiota are thought to play a crucial role in the development and maintenance of the abnormal inflammatory responses that are the hallmark of inflammatory bowel disease. Direct tests of the role of the gut microbiome in these disorders are typically limited by the fact that sampling of the microbiota generally occurs once disease has become manifest. This limitation could potentially be circumvented by studying patients who undergo total proctocolectomy with ileal pouch anal anastomosis (IPAA) for the definitive treatment of ulcerative colitis. A subset of patients who undergo IPAA develops an inflammatory condition known as pouchitis, which is thought to mirror the pathogenesis of ulcerative colitis. Following the development of the microbiome of the pouch would allow characterization of the microbial community that predates the development of overt disease.ResultsWe monitored the development of the pouch microbiota in four patients who underwent IPAA. Mucosal and luminal samples were obtained prior to takedown of the diverting ileostomy and compared to samples obtained 2, 4 and 8 weeks after intestinal continuity had been restored. Through the combined analysis of 16S rRNA-encoding gene amplicons, targeted 16S amplification and microbial cultivation, we observed major changes in structure and function of the pouch microbiota following ileostomy. There is a relative increase in anaerobic microorganisms with the capacity for fermentation of complex carbohydrates, which corresponds to the physical stasis of intestinal contents in the ileal pouch. Compared to the microbiome structure encountered in the colonic mucosa of healthy individuals, the pouch microbial community in three of the four individuals was quite distinct. In the fourth patient, a community that was much like that seen in a healthy colon was established, and this patient also had the most benign clinical course of the four patients, without the development of pouchitis 2 years after IPAA.ConclusionsThe microbiota that inhabit the ileal-anal pouch of patients who undergo IPAA for treatment of ulcerative colitis demonstrate significant structural and functional changes related to the restoration of fecal flow. Our preliminary results suggest once the pouch has assumed the physiologic role previously played by the intact colon, the precise structure and function of the pouch microbiome, relative to a normal colonic microbiota, will determine if there is establishment of a stable, healthy mucosal environment or the reinitiation of the pathogenic cascade that results in intestinal inflammation.

The role of the microbiome in human health and disease: an introduction for clinicians

“…Multiple studies show that the intestinal microbiota of patients with IBD is distinct from that of people without IBD. [59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78] Studies of IBD were some of the first studies of disease that extensively used culture independent characterization of the intestinal microbiota to show an association between disease and an altered microbial community. Early studies used both 16S based sequencing methods and fluorescent in situ hybridization to show that the community structure found in patients with disease was distinct from that of controls.…”

Intestinal microbiota, fecal microbiota transplantation, and inflammatory bowel disease

“…122 Like UC itself, however, patients with pouchitis may have a pouch microbiota that is distinct from that of patients without active inflammation. 122,123 Although this suggests that FMT may also be a treatment of pouchitis, small studies have failed to demonstrate remission following FMT. 124 One key limitation in FMT for pouchitis is the size of the pouch, which may limit engraftment of a donor microbiota.…”

The microbiota in inflammatory bowel disease

“…Regression in life expectancy in the twenty-first century is predicted if the rate of obesity remains unchecked [63]. Malnutrition has long been recognized as a complication of IBD.…”