Dataset Information

Prebiotic Supplementation Following Ileocecal Resection in a Murine Model is Associated With a Loss of Microbial Diversity and Increased Inflammation.

ABSTRACT: Background:Individuals with Crohn's disease frequently require ileocecal resection (ICR), and inflammation often recurs in the neoterminal ileum following surgery. Fructooligosaccharide (FOS) is a fermentable prebiotic that stimulates the growth of bifidobacteria and may promote anti-inflammatory activity. The aim of this study was to determine if supplementation of a postICR diet with FOS in a mouse model would be effective in stimulating the growth of bifidobacteria and reducing systemic and local inflammation. Methods:ICR was performed in IL10-/- mice (129S1/SvlmJ) with colitis. Following surgery, nonICR control and ICR mice were fed a chow diet ± 10% FOS for 28 days. Serum, colon, and terminal ileum (TI) were analyzed for cytokine expression by MesoScale discovery platform. DNA extracted from stool was analyzed using 16s rRNA sequencing and qPCR. Expression of occludin and ZO1 was assessed using qPCR. Short-chain fatty acid (SCFA) concentrations were assessed using gas chromatography. Results:ICR led to increased systemic inflammation (P < 0.05) and a significant decline in fecal microbial diversity (P < 0.05). Mice on the FOS diet had a greater reduction in microbial diversity and also had worsened inflammation as evidenced by increased serum IL-6 (P < 0.05) and colonic IFN? and TNF? (P < 0.05). Expression of occludin and ZO1 were significantly reduced in FOS-supplemented mice. There was a correlation between loss of diversity and the bifidogenic effectiveness of FOS (r = -0.61, P < 0.05). Conclusions:FOS-supplementation of a postICR diet resulted in a decrease in fecal bacterial diversity, reduction in barrier function, and increased gut inflammation.

SUBMITTER: Laffin M

PROVIDER: S-EPMC6176898 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Prebiotic Supplementation Following Ileocecal Resection in a Murine Model is Associated With a Loss of Microbial Diversity and Increased Inflammation.

Laffin Michael M Perry Troy T Park Heekuk H Hotte Naomi N Fedorak Richard N RN Thiesen Aducio A Dicken Bryan B Madsen Karen L KL

Inflammatory bowel diseases 20171201 1

<h4>Background</h4>Individuals with Crohn's disease frequently require ileocecal resection (ICR), and inflammation often recurs in the neoterminal ileum following surgery. Fructooligosaccharide (FOS) is a fermentable prebiotic that stimulates the growth of bifidobacteria and may promote anti-inflammatory activity. The aim of this study was to determine if supplementation of a postICR diet with FOS in a mouse model would be effective in stimulating the growth of bifidobacteria and reducing system ...[more]

PMID: 29272494

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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.

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Project description:Aims Gut microbiota-mediated inflammation promotes obesity-associated low-grade inflammation, which represents a hallmark of the metabolic syndrome (MetS). Lifestyle-induced weight loss (WL) is regarded as an efficient therapy to reverse MetS and to prevent disease progression. The objective of this study was to investigate if lifestyle-induced WL modulates the gut microbiome and its interaction with the host. Methods We analyzed and compared the fecal metaproteome of 33 individuals with MetS in a longitudinal study before and after lifestyle-induced WL in a well-defined cohort (ICTRP Trial Number: U1111-1158-3672). Results The 6-month WL intervention resulted in reduced BMI (-13.9%), increased insulin sensitivity (HOMA-IR; -53.70%) and reduced levels of circulating CRP (-66.86%), indicating MetS reversal. The metaprotein spectra of the host revealed a decrease of human proteins associated with gut inflammation and reduced abundance of human pancreatic alpha-amylase. Surprisingly, taxonomic analysis of the fecal metaproteome revealed only minor changes in the bacterial composition with an increase of low-abundant families (Desulfovibrionaceae, Leptospiraceae, Syntrophomonadaceae, Thermotogaceae, Verrucomicrobiaceae). Yet, we detected increased abundance of microbial metaprotein spectra that correspond to enhanced hydrolysis of complex carbohydrates (endoglucanase A, β-1,4-mannooligosaccharide phosphorylase, galactokinase, 5-keto-D-gluconate 5-reductase), indicating functional changes of the gut microbiome. Conclusions Our results indicate that lifestyle induced WL may improve interaction between the gut microbiome and the host in individuals with MetS, while bacterial composition remained almost stable. Metaproteome analysis of host proteins reveals reduced gut inflammation whereas microbial metaprotein spectra indicate functional changes towards degradation of complex carbohydrates. The filenames correspond to the ID of the patient (1-33), whereas “C” corresponds to baseline and “ABC” to weight loss.

Dataset Information

Prebiotic Supplementation Following Ileocecal Resection in a Murine Model is Associated With a Loss of Microbial Diversity and Increased Inflammation.

Publications

Prebiotic Supplementation Following Ileocecal Resection in a Murine Model is Associated With a Loss of Microbial Diversity and Increased Inflammation.

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