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Impact of ileocecal resection and concomitant antibiotics on the microbiome of the murine jejunum and colon.

ABSTRACT: Ileocecal resection (ICR) is a commonly required surgical intervention in unmanageable Crohn's disease and necrotizing enterocolitis. However, the impact of ICR, and the concomitant doses of antibiotic routinely given with ICR, on the intestinal commensal microbiota has not been determined. In this study, wild-type C57BL6 mice were subjected to ICR and concomitant single intraperitoneal antibiotic injection. Intestinal lumen contents were collected from jejunum and colon at 7, 14, and 28 days after resection and compared to non-ICR controls. Samples were analyzed by 16S rRNA gene pyrosequencing and quantitative PCR. The intestinal microbiota was altered by 7 days after ICR and accompanying antibiotic treatment, with decreased diversity in the colon. Phylogenetic diversity (PD) decreased from 11.8 ± 1.8 in non-ICR controls to 5.9 ± 0.5 in 7-day post-ICR samples. There were also minor effects in the jejunum where PD values decreased from 8.3 ± 0.4 to 7.5 ± 1.4. PCoA analysis indicated that bacterial populations 28 days post-ICR differed significantly from non-ICR controls. Moreover, colon and jejunum bacterial populations were remarkably similar 28 days after resection, whereas the initial communities differed markedly. Firmicutes and Bacteroidetes were the predominant phyla in jejunum and colon before ICR; however, Firmicutes became the vastly predominant phylum in jejunum and colon 28 days after ICR. Although the microbiota returned towards a homeostatic state, with re-establishment of Firmicutes as the predominant phylum, we did not detect Bacteroidetes in the colon 28 days after ICR. In the jejunum Bacteroidetes was detected at a 0.01% abundance after this time period. The changes in jejunal and colonic microbiota induced by ICR and concomitant antibiotic injection may therefore be considered as potential regulators of post-surgical adaptive growth or function, and in a setting of active IBD, potential contributors to post-surgical pathophysiology of disease recurrence.

SUBMITTER: Devine AA

PROVIDER: S-EPMC3754918 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Impact of ileocecal resection and concomitant antibiotics on the microbiome of the murine jejunum and colon.

Devine Anthony A AA Gonzalez Antonio A Speck K Elizabeth KE Knight Rob R Helmrath Michael M Lund P Kay PK Azcarate-Peril M Andrea MA

PloS one 20130827 8

Ileocecal resection (ICR) is a commonly required surgical intervention in unmanageable Crohn's disease and necrotizing enterocolitis. However, the impact of ICR, and the concomitant doses of antibiotic routinely given with ICR, on the intestinal commensal microbiota has not been determined. In this study, wild-type C57BL6 mice were subjected to ICR and concomitant single intraperitoneal antibiotic injection. Intestinal lumen contents were collected from jejunum and colon at 7, 14, and 28 days af ...[more]

PMID: 24015295

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Project description:Gastrointestinal surgery imparts dramatic and lasting imbalances, or dysbiosis, to the composition of finely tuned microbial ecosystems. The aim of the present study was to use a mouse ileocecal resection (ICR) model to determine if tributyrin (TBT) supplementation could prevent the onset of microbial dysbiosis or alternatively enhance the recovery of the gut microbiota and reduce gastrointestinal inflammation. Male wild-type (129 s1/SvlmJ) mice aged 8-15 weeks were separated into single cages and randomized 1:1:1:1 to each of the four experimental groups: control (CTR), preoperative TBT supplementation (PRE), postoperative TBT supplementation (POS), and combined pre- and postoperative supplementation (TOT). ICR was performed one week from baseline assessment with mice assessed at 1, 2, 3, and 4 weeks postoperatively. Primary outcomes included evaluating changes to gut microbial communities occurring from ICR to 4 weeks. A total of 34 mice that underwent ICR (CTR n = 9; PRE n = 10; POS n = 9; TOT n = 6) and reached the primary endpoint were included in the analysis. Postoperative TBT supplementation was associated with an increased recolonization and abundance of anaerobic taxa including Bacteroides thetaiotomicorn, Bacteroides caecimuris, Parabacteroides distasonis, and Clostridia. The microbial recolonization of PRE mice was characterized by a bloom of aerotolerant organisms including Staphylococcus, Lactobacillus, Enteroccaceae, and Peptostreptococcacea. PRE mice had a trend towards decreased ileal inflammation as evidenced by decreased levels of IL-1β (p = 0.09), IL-6 (p = 0.03), and TNF-α (p < 0.05) compared with mice receiving TBT postoperatively. In contrast, POS mice had trends towards reduced colonic inflammation demonstrated by decreased levels of IL-6 (p = 0.07) and TNF-α (p = 0.07). These changes occurred in the absence of changes to fecal short-chain fatty acid concentrations or histologic injury scoring. Taken together, the results of our work demonstrate that the timing of tributyrin supplementation differentially modulates gastrointestinal inflammation and gut microbial recolonization following murine ICR.

Project description:BackgroundPatients with Crohn's disease suffer from a higher rate of anastomotic leakages after ileocecal resection than patients without Crohn's disease. Our hypothesis was that microscopic inflammation at the resection margins of ileocecal resections in Crohn's disease increases the rate of anastomotic leakages.Patients and methodsIn a retrospective cohort study, 130 patients with Crohn's disease that underwent ileocecal resection between 2015 and 2019, were analyzed. Anastomotic leakage was the primary outcome parameter. Inflammation at the resection margin was characterized as "inflammation at proximal resection margin", "inflammation at distal resection margin" or "inflammation at both ends".Results46 patients (35.4%) showed microscopic inflammation at the resection margins. 17 patients (13.1%) developed anastomotic leakage. No difference in the rate of anastomotic leakages was found for proximally affected resection margins (no anastomotic leakage vs. anastomotic leakage: 20.3 vs. 35.3%, p = 0.17), distally affected resection margins (2.7 vs. 5.9%, p = 0.47) or inflammation at both ends (9.7 vs. 11.8%, p = 0.80). No effect on the anastomotic leakage rate was found for preoperative hemoglobin concentration (no anastomotic leakage vs. anastomotic leakage: 12.3 vs. 13.5 g/dl, p = 0.26), perioperative immunosuppressive medication (62.8 vs. 52.9%, p = 0.30), BMI (21.8 vs. 22.4 m2/kg, p = 0.82), emergency operation (21.2 vs. 11.8%, p = 0.29), laparoscopic vs. open procedure (p = 0.58), diverting ileostomy (31.9 vs. 57.1%, p = 0.35) or the level of surgical training (staff surgeon: 80.5 vs. 76.5%, p = 0.45).ConclusionMicroscopic inflammation at the resection margins after ileocecal resection in Crohn's disease is common. Histologically inflamed resection margins do not appear to affect the rate of anastomotic leakages. Our data suggest that there is no need for extensive resections or frozen section to achieve microscopically inflammation-free resection margins.

Dataset Information

Impact of ileocecal resection and concomitant antibiotics on the microbiome of the murine jejunum and colon.

Publications

Impact of ileocecal resection and concomitant antibiotics on the microbiome of the murine jejunum and colon.

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