Targeting the gut microbiota to improve patient outcomes following stoma reversal surgery

Southern, Ella and Rigby, Rachael and Worthington, John (2025) Targeting the gut microbiota to improve patient outcomes following stoma reversal surgery. Masters thesis, Lancaster University.

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Abstract

Temporary faecal diversion by loop ileostomy disrupts the sensitive intestinal environment, resulting in significant atrophy and rendering the downstream bowel defunctioned. Upon stoma reversal, 40% of patients experience morbidities such as intestinal inflammation and reduced bowel function associated with poor intestinal restoration. Strategies to improve epithelial repair following loop ileostomy remain underexplored, with probiotics, synbiotics, and mechanical stimulation providing limited improvements. Here, the impact of prebiotic stimulation of the defunctioned ileum was investigated by assessing changes to the epithelial morphology, immune cell populations, and bacterial composition. Two patient cohorts were studied: an unfed group (n=35), who did not receive pre-operative enteral feeding, and a prebiotic-fed group (n=5), who received Orafti® Synergy1 (inulin-oligofructose) diluted in Ensure® nutrient shake via a stoma feeding tube for 2-27 days before reversal. Full-thickness samples were obtained from proximal (functional) and distal (defunctioned) ileal segments at reversal. Tissues were analysed by histology, flow cytometry, and phylum-specific 16S rDNA qPCR. Faecal diversion did not alter macrophage, T helper, or TLR5+ cell frequencies in the lamina propria, but was associated with an increase in CD11c+ dendritic cells, which may reflect an anti-inflammatory response. Morphological analyses revealed that prebiotic feed significantly increased crypt depth in the defunctioned ileum compared with unfed tissue (p=0.0365), suggesting increased epithelial cell proliferation. Compared with the unfed bowel, villus height was no longer atrophied, indicating that villus restoration was underway. Interestingly, CD11c+ dendritic cells were reduced after prebiotic feeding, perhaps suggesting a return toward immune homeostasis. Phylum-specific microbial profiling revealed a significant increase in Firmicutes abundance in prebiotic-fed ileum, consistent with a shift toward eubiosis. Future species-level analysis via 16S sequencing is required to confirm microbial restoration and validate the link to epithelial outcomes. Collectively, these findings conclude that enteral prebiotic feeding may partially restore microbiota, promote epithelial renewal, and modulate immune cell populations. This highlights the therapeutic potential of prebiotic stoma feeding in improving mucosal health before ileostomy reversal, with implications for reducing postoperative complications. Future work should explore optimal feeding time and investigate species-level microbial changes by 16S sequencing.