Chronic mesenteric ischemia-induced intestinal dysbiosis resolved after revascularization

Abstract

Objective: Chronic mesenteric ischemia (CMI) is a debilitating condition arising from intestinal malperfusion from mesenteric artery stenosis or occlusion. Mesenteric revascularization has been the standard of care but can result in substantial morbidity and mortality. Most of the perioperative morbidity has been secondary to postoperative multiple organ dysfunction, potentially from ischemia–reperfusion injury. The intestinal microbiome is a dense community of microorganisms in the gastrointestinal tract that help regulate pathways ranging from nutritional metabolism to the immune response. We hypothesized that patients with CMI will have microbiome perturbations that contribute to this inflammatory response and could potentially normalize in the postoperative period. Methods: We performed a prospective study of patients with CMI who had undergone mesenteric bypass and/or stenting from 2019 to 2020. Stool samples were collected at three time points: preoperatively at the clinic, perioperatively within 14 days after surgery, and postoperatively at the clinic at >30 days after revascularization. Stool samples from healthy controls were used for comparison. The microbiome was measured using 16S rRNA sequencing on an Illumina-MiSeq sequence platform and analyzed using the QIIME2 (quantitative insights into microbial ecology 2)–DADA2 bioinformatics pipeline with the Silva database. Beta-diversity was analyzed using a principal coordinates analysis and permutational analysis of variance. Alpha-diversity (microbial richness and evenness) was compared using the nonparametric Mann-Whitney U test. Microbial taxa unique to CMI patients vs controls were identified using linear discriminatory analysis effect size analysis. P < .05 was considered statistically significant. Results: Eight patients with CMI had undergone mesenteric revascularization (25% men; average age, 71 years). Nine healthy controls were also analyzed (78% men; average age, 55 years). Bacterial alpha-diversity (number of operational taxonomic units) was dramatically reduced preoperatively compared with that of the controls (P = .03). However, revascularization partially restored the species richness and evenness in the perioperative and postoperative phases. Beta-diversity was only different between the perioperative and postoperative groups (P = .03). Further analyses revealed increased abundance of Bacteroidetes and Clostridia taxa preoperatively and perioperatively compared with the controls, which was reduced during the postoperative period. Conclusions: The results from the present study have shown that patients with CMI have intestinal dysbiosis that resolves after revascularization. The intestinal dysbiosis is characterized by the loss of alpha-diversity, which is restored perioperatively and maintained postoperatively. This microbiome restoration demonstrates the importance of intestinal perfusion to sustain gut homeostasis and suggests that microbiome modulation could be a possible intervention to ameliorate acute and subacute postoperative outcomes in these patients.

Keywords

• Chronic mesenteric ischemia
• Microbiota
• Revascularization