EPD515 - New Jersey Society of Colon and Rectal Surgeons Best ePoster Award: Microbiota Transplant Therapy Reconstitutes the Gut Microbiome Composition and Function After Colorectal Surgery

ePoster of Distinction Presenter(s)

• SB

  Sonja Boatman, MD (she/her/hers)

  Resident
  Universit of Minnesota
  University of Minnesota
  Minneapolis, MN, United States

  All of the relevant financial relationships listed below have been mitigated.
  This individual has no financial relationships with ineligible companies.

Author(s)

• 

  Alexander M. Troester, MD (he/him/his)

  General Surgery Resident
  University of Minnesota
  University of Minnesota
  Minneapolis, MN, United States

  Disclosure information not submitted.
• 

  Julia Frebault, MD (she/her/hers)

  General Surgery Research Resident
  University of Minnesota
  University of Minnesota
  Minneapolis, MN, United States

  Disclosure information not submitted.
• MH

  Max G. Hill, BS

  Research Assistant
  UMN Department of Surgery
  St. Paul, Minnesota, United States

  Disclosure information not submitted.
• CB

  Catherine Beauharnais, MD, MPH, MS

  Fellow
  University of Minnesota
  University of Minnesota
  Minneapolis, MN, United States

  Disclosure information not submitted.
• HN

  Harika Nalluri-Butz, MD

  Assistant Professor
  University of Minnesota
  Minneapolis, Minnesota, United States

  Disclosure information not submitted.
• 

  Paolo Goffredo, MD (he/him/his)

  Assistant Professor
  University of Minnesota
  Minneapolis, MN, United States

  All of the relevant financial relationships listed below have been mitigated.
  This individual has no financial relationships with ineligible companies.
• 

  Wolfgang Gaertner, MD, MSc, MBA

  Professor and Chief, Colon & Rectal Surgery
  University of Minnesota
  University of Minnesota
  Minneapolis, MN, United States

  All of the relevant financial relationships listed below have been mitigated.
  This individual has no relevant relationships with ineligible companies.
• CS

  Christopher Staley, n/a

  Associate Professor
  University of Minnesota
  Minneapolis, Minnesota, United States

  Disclosure information not submitted.

Senior Author(s)

• 

  Cyrus Jahansouz, MD

  Assistant Professor
  University of Minnesota
  University of Minnesota
  Minneapolis, Minnesota, United States

  All of the relevant financial relationships listed below have been mitigated.
  This individual has no financial relationships with ineligible companies.

Purpose/Background: Preoperative bowel preparation (BP), consisting of mechanical BP and oral antibiotics (OA), is an intervention that leads to the elimination of both pathogenic and beneficial microbes. These disruptions of the gut microbiome have been linked to complications after colorectal surgery, such as anastomotic leak and surgical site infections. Short-chain fatty acids (SCFA) are microbial metabolites that are crucial in regulation of colonocyte inflammation and immune function, as well as wound healing. Our group previously demonstrated successful restoration of healthy gut microbiota via a novel postoperative microbiota transplant therapy (MTT) protocol in a cohort of patients undergoing minimally invasive sigmoidectomy. Here, we report on longitudinal microbiome engraftment in an expanded cohort of patients. We additionally hypothesized that MTT recipients would have greater SCFA production compared to the control group, indicative of restored microbiota function after MTT.

Methods/Interventions: Twelve patients who underwent minimally invasive sigmoidectomy followed by MTT were compared to 12 matched controls (sigmoidectomy without MTT). The indication for surgery was either colon cancer (n=3, both groups) or diverticulitis (n=9, both groups). All patients received mechanical BP, OA, and perioperative intravenous antibiotics. 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 at baseline, within 24 hours after MTT (inpatient), postoperative day (POD) 14, 30, 90, and 180. 16S rRNA gene-based amplicon sequencing was performed to characterize the taxonomic profiles of gut microbiota. SourceTracker assessed the similarity of postoperative composition to donor and patients' own preoperative microbiota. Alpha and beta diversity statistics were calculated in mothur. Fecal SCFA were quantified by gas chromatography-mass spectrometry.

Results/Outcomes: MTT promoted durable microbial engraftment by POD14, persisting through the 6-month study period. By POD14, alpha diversity trended higher in the MTT cohort vs. controls (mean ± SD: 3.29 ± 0.25 vs. 2.86 ± 0.94; P=0.29). Following MTT, fecal community composition diverged significantly from controls at POD14, POD30, and POD90, (R=0.28, 0.40, and 0.53; P< 0.001, < 0.001, and 0.017 respectively). MTT led to distinct taxonomic shifts relative to the control group; on POD14 and POD30 MTT recipients exhibited significantly higher levels of Akkermansia (P=0.018 and 0.003) and Collinsella (P=0.004 and 0.022) vs. controls. Relative abundances of canonical butyrate-producing taxa, including Blautia, Ruminococcaceae, and Lachnospiraceae, trended higher in MTT recipients on POD14 and POD30 (P>0.07). Streptococcus, a hallmark of postoperative dysbiosis, also trended lower in the MTT group at POD14 (P=0.07). SCFA (acetate, propionate, butyrate, valerate) declined sharply after surgery in both groups. By POD14, SCFA were significantly higher in MTT recipients vs. controls (acetate P=0.0025, propionate P=0.0003, butyrate P=0.0018).

Conclusion/Discussion: MTT following minimally invasive sigmoidectomy effectively reconstituted the gut microbiota, facilitating early recovery of keystone commensal taxa and attenuating the expansion of pathobionts. Furthermore, MTT was associated with a robust restoration of SCFA production, indicating functional recovery of the intestinal microbial ecosystem.

Figure 1
A) Engraftment occurs by POD14 and persists through 6 months; B) Principal coordinate analysis (PCoA) of Bray-Curtis distances shows fecal microbial community structure in controls (all timepoints) and MTT recipients before (orange circles) and after (green circles) transplantation (r2=0.37). Samples from MTT diverge away from both inpatient and baseline samples; C) Relative abundances (mean ± standard deviation) of Collinsella and Akkermansia in controls at baseline and through POD90 and MTT recipients at baseline through POD180. Both taxa increase significantly by POD14 after MTT and remain elevated relative to the control group through POD30; D) Fecal concentrations (± standard error) of short-chain fatty acids (SCFAs; butyric acid, acetic acid, and propionic acid) decline sharply following surgery. By POD14, patients receiving MTT exhibit an ~8-fold increase in SCFA levels compared to controls. * P<0.05; ** P<0.005.