QS116 - Microbiota Transplant Therapy Effectively Reconstitutes the Gut Microbiome After Colorectal Surgery

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Purpose/Background: Complications such as anastomotic leak, surgical site infection, and delayed return of bowel function remain major sources of morbidity, mortality, and healthcare costs after colorectal operations. The gut microbiota is crucial for metabolism and wound healing, but can harbor pathogenic organisms such as Enterococcus and Streptococcus that have been linked to anastomotic leak. While bowel preparation (BP), including mechanical purging and antibiotics, effectively reduces pathogens before surgery, it also eliminates beneficial microbes. Microbiota Transplant Therapy (MTT) has proven to be the most effective method for restoring gut microbiota and its essential functions. Currently, no protocols exist for reintroducing these beneficial microbes following BP. Our institution has secured FDA approval (IND 28152) for a novel postoperative MTT protocol aimed at early reintroduction of a diverse, healthy microbiota. We hypothesized that this approach would accelerate and improve gut recovery and function in patients undergoing minimally invasive (MIS) sigmoidectomy for medically refractory and complicated diverticulitis.

Methods/Interventions: Seven patients underwent mechanical BP with oral antibiotics (Neomycin/Metronidazole) plus perioperative parenteral antibiotics followed by MIS sigmoidectomy with primary anastomosis. MTT, consisting of a 35mL solution from a healthy donor, was administered via post-pyloric nasojejunal feeding tube 48 hours after completing perioperative parenteral antibiotics. Fecal samples were collected pre-BP, within 24 hours after transplantation, postoperative day (POD) 10-14, and POD30. 16S rRNA gene-based amplicon sequencing and targeted metabolomics were performed to characterize the taxonomic profiles of gut microbiota. Alpha and beta diversity statistics were calculated in mothur. SourceTracker assessed the similarity of postoperative composition to patients’ own preoperative microbiota. MTT patients were compared to a control group of 9 patients who underwent MIS sigmoidectomy with primary anastomosis for diverticulitis with the same perioperative management and similar longitudinal fecal sampling.

Results/Outcomes: Zero patients suffered infectious or surgical complications. No differences were observed in the Shannon index at baseline (Tukey’s post-hoc p=0.99), however, diversity was significantly lower in the control cohort at POD10-14 following surgery (Figure 1A). Similarly, microbial community structure was comparable between the two groups at baseline (analysis of similarity [ANOSIM] R=0.20, p=0.06), but significant differences in community structure were observed in POD10-14 (ANOSIM R=0.18, p=0.04) and POD30 samples (R=0.44, p< 0.01; Figure 1B). MTT patient samples shared similar trajectories on principal coordinate analysis immediately following surgery before returning to a composition similar to baseline within two weeks. In contrast, control patients tended to drift away from baseline, corresponding to increases in relative abundances of Streptococcus in the weeks immediately following surgery (Figure 1C).

Conclusion/Discussion: In this early case series, MTT after MIS sigmoidectomy for diverticulitis effectively restored microbial diversity and community structure when compared to patients who underwent MIS sigmoidectomy without MTT. These preliminary findings provide a strong foundation for initiating a clinical trial to evaluate and compare the efficacy of gut microbial reconstitution after colorectal surgery.