Dysbiosis and reduced small intestinal function are required to induce intestinal insufficiency in mice

Abstract

Extensive bowel resection can lead to short bowel syndrome and intestinal failure. Resection-induced dysbiosis may be related to the specific anatomic site of resection and influences the disease progression. While patients with end-jejunostomy are at high risk for intestinal failure, preservation of the ileocecal valve and colon counteracts this risk. The present study investigated the role of the cecum in maintaining microbial homeostasis after different types of small bowel resection. Male C57BL6/J mice were anesthetized by intraperitoneal injection of ketamine/xylazine and received extended ileocecal resection (extended ICR), limited ileocecal resection (limited ICR) or mid small bowel resection (SBR). Stool samples were collected before surgery and between postoperative days 2-7, for 16S rRNA gene sequencing. Only extended ICR, but neither limited ICR nor SBR, induced intestinal insufficiency. α-diversity was reduced in both ICR variants, but not after SBR. All resections resulted in an increase in Proteobacteria. Pathobionts, such as Clostridia, Shigella, and Enterococcus, increased after SBR while Muribaculaceae, Lactobacillus, and Lachnospiraceae decreased. Limited ICR resulted in an increase of members of the Clostridium sensu stricto group, Terrisporobacter and Enterococcus and a decrease of Muribaculaceae. The increase of Enterococcus was even more pronounced after extended ICR while Muribaculaceae and Akkermansia were dramatically reduced. Both ICR variants caused a decrease of steroid biosynthesis and glycosaminoglycan degradation associated pathways, suggesting altered bile acid transformation and mucus utilization

Changes in HLA-B27 Transgenic Rat Fecal Microbiota Following Tofacitinib Treatment and Ileocecal Resection Surgery: Implications for Crohn’s Disease Management

“…This was previously documented in both wild-type and colitis-susceptible IL-10−/− mice subjected to ICR [53,54]. The resection-induced dysbiosis in our study was highly similar to that recently reported in mice [13] and could define a signature of specific taxa. Indeed, analogous changes were measured in three distinct resection models and showed reduced diversity and a dramatic decrease in Muribaculaceae and Akkermansia, two mucus-degrading species [55], which was offset by an increase in Proteobacteria (mostly the aerotolerant E. coli) and Firmicutes, including Clostridiaceae, in both limited ICR, extended ICR and even small bowel resection (SBR) experimental models.…”

“…The physiopathology-sustaining postoperative recurrences of Crohn's disease remain unknown, although interactions between the enteric and systemic immune system and the gut microbiota at mucosal sites are highly suggested [8,9]. Additionally, it is also well established that overall intestinal surgeries, including ileocecal resection and colorectal surgery, can strongly modify the gut microbiome structure and affect its functionality [10][11][12][13][14]. Collectively, gut microbiota perturbation is thus central in (i) the contribution of the clinical parameters of Crohn's disease (initiation, maintenance and perpetration of inflammation); (ii) the postoperative recurrence of the disease, defining resilience and remission following surgical intervention; and (iii) drug-based therapeutic responses, considering bidirectional interactions between microbes and active molecules.…”

Metabolomic Alterations of Volatile Organic Compounds and Bile Acids as Biomarkers of Microbial Shifts in a Murine Model of Short Bowel Syndrome

“…Microbial analysis of stool samples collected between postoperative days 2 and 7 in mice undergoing small bowel resection has revealed a reduction in alpha diversity and an increase in Proteobacteria; pathobionts such as Clostridia, Shigella and Enterococcus increased after small bowel resection while Muribaculaceae, Lactobacillus and Lachnospiraceae decreased [60]. In our study, the most profound alterations were found in the colon, with SBS causing increases in Faecalibaculum and Escherichia-Shigella and decreases in Ruminococcaceae.…”

“…A major factor influencing its outcome is the absence or presence of the ileocecal valve [58,59]. Berlin and coworkers examined microbial changes of stool samples in a comparison of mice undergoing 50% small bowel resection leaving the ileocecal junction intact (comparable to our method), limited ileocecal resection and extended ileocecal resection [60]. Alpha diversity as assessed by the Shannon index remained stable following 50% small bowel resection at postoperative day 5 and was profoundly decreased following the methods associated with resection of the ileocecal valve.…”

“…The mass spectrometer was operated in selected ion monitoring (SIM) mode, targeting specific m/z values (60,63,73,74,76,79 and 80) at their respective retention times. Quantification of acetic (C2), propionic (C3), butyric (C4), valeric (C5) and hexanoic (C6) acids was conducted through single-point calibration in comparison to their respective internal standards.…”