Gut microbiome and plasma metabolome alterations in ileostomy and after closure of ileostomy

ABSTRACT A temporary loop ileostomy is a routine procedure for protecting the anastomosis in patients undergoing radical resection of rectal cancer. Fecal diversion by a diverting ileostomy may induce microbiota dysbiosis in the defunctioned colon; however, data on temporal and spatial microbiome and metabolome changes in these patients are sparse. Thirty patients who underwent ileostomy closure were enrolled. Fecal and plasma samples were collected successively before ileostomy closure, at the first postoperative defecation, and 1 month postoperatively. The 16S rRNA gene sequencing was used to assess changes in gut microbes, and metabolic components in the plasma were analyzed using global untargeted metabolomics. Advanced data analysis methods were used to examine the differences and correlations between flora and metabolites. The gut microbiota in the ileostomy effluent and defunctioned colon had lesser species diversity and richness, with an abundance of aerobic, gram-negative, and potentially pathogenic bacteria. After the intestinal continuity was restored with routine meal feeding, the gut microbes recovered to a standard composition within 1 month. Moreover, xanthine, traumatic acid, L-glutamine, and norepinephrine levels increased markedly in patients with ileostoma. The ileostomy closure reversed the ileostomy-associated metabolic alterations, including an increased abundance of L-leucine, creatine, and 2-ketobutyric acid. Furthermore, Agathobacter and Peptostreptococcus were most closely associated with the reconstruction of postoperative gut microbes. We described a spatiotemporal map of the intestinal microbial ecological reconstruction and metabolic recovery before and after ileostomy reversal for perioperative intervention in patients with ileostomy closure surgery. IMPORTANCE In this paper, the changes in the intestinal microbiome and plasma metabolome before and after temporary ileostomy were reported for the first time, and the dynamic changes in intestinal contents were described. At the same time, the key bacterial genera involved in the reestablishment of microflora after the restoration of intestinal continuity were found, and the key relationship between them and plasma metabolites was also found. More importantly, we found that patients with ileal fistula may be at risk of metabolic imbalance and that this particular metabolic state may potentially affect the course of tumor treatment. Finally, the samples in this study were obtained in their natural state and can be easily applied to the clinic to avoid unnecessary invasive examinations.