Improving operative outcomes in patients with stomas

ABSTRACT Stoma formation diverts the flow of faeces to an opening on the skin, away from a section of bowel. Stomas are used to reduce the risks of bowel surgery and their effects are thought to be temporary and benign. However, negative effects [e.g. diversion colitis (inflammation in the excluded segment), poor quality of life, and an unclear effect on homeostasis] occur. We investigated these changes and whether distal feeding (DF) – the introduction of nutrition directly into the defunctioned bowel prior to stoma reversal – could mitigate these effects. A series of clinical, qualitative, immunological, metabolomic and microbiomic experiments conducted across 133 patients identified consistent changes in immune and microbiome response which differed according to stoma formation and underlying disease process [colorectal cancer (CRC) with or without chemotherapy, intestinal failure (IF)], including a unique immune signature in circulating memory T-cell homing in stoma patients. DF induced the proliferation and altered homing of memory T cells, particularly in patients who had received chemotherapy. DF led to changes in serum metabolites, increased circulating markers of gut health (citrulline, serotonin), and modified the faecal microbiota. DF also promoted a faster return of bowel function and earlier hospital discharge in patients with CRC, while in IF it accelerated intestinal autonomy from parenteral nutrition. This in-depth analysis of sequential experiments characterises gut homeostasis and post-operative systemic immunity after stoma formation in CRC and IF patients, and quantifies and explains the benefit of DF in these groups. This research program has wide-ranging implications for patients worldwide with stomas. Given its simplicity, affordability and wide applicability, DF has the potential to become a transformative adjunct in surgical recovery and improved long-term gut health in patients with stomas.