Microbiota Transplant Therapy Significantly Reduces Pathogenic Intestinal Bacteria Following Colorectal Surgery

Authors:
Alexander Troester, Christopher Staley, Cyrus Jahansouz, Harika Nalluri-Butz, Julia Frebault, Paolo Goffredo, Sonja Boatman, Wolfgang Gaertner

Body of Abstract:
Background
Bowel preparation (BP) and surgery deplete both pathogenic and beneficial gut microbiota, leaving the early postoperative landscape susceptible to colonization by these harmful strains. In fact, infectious complications after colorectal surgery have been linked to pathogenic organisms such as Streptococcus and Enterococcus. Microbiota Transplant Therapy (MTT) effectively restores gut microbiota diversity and its vital functions, but no protocols exist for reintroduction following BP. Therefore, we secured FDA approval (IND 28152) for a novel postoperative MTT protocol designed to effectively reintroduce a diversified microbiota. We hypothesize that this diversified MTT reintroduction would cause Streptococcus and Enterococcus abundance to be significantly reduced.
Methods
Seven patients underwent mechanical BP with oral antibiotics plus perioperative parenteral antibiotics followed by sigmoidectomy for diverticulitis. MTT 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 characterized 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 an identical operation with the same perioperative management and similar longitudinal fecal sampling.
Results
Zero patients suffered infectious or surgical complications. Baseline microbial community structure was comparable between the two groups (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; Figure 1A) and POD30 samples (R=0.44, p<0.01). Specifically, at POD10-14, Streptococcus relative abundance was significantly reduced in the MTT group at POD10-14 (p=0.005; Figure 1B), while a reduction in Enterococcus approached significance by POD30 (p=0.061; Figure 1C). Conclusions MTT following sigmoidectomy for diverticulitis effectively restored microbial diversity and reduced the relative abundance of known pathogenic bacteria. These preliminary findings suggest that MTT represents a promising intervention warranting clinical trial investigation.