Microbiota Transplantation Therapy Opposes Oral-Gut Translocation in Colorectal Surgery Patients

Authors:
Julia Frebault, Max Hill, Alexander Troester, Christopher Staley, Cyrus Jahansouz

Body of Abstract:
Background

In colorectal surgery, following surgical bowel preparation and colon resection, there are alterations of key genera in the gut microbiome. A rise in pathogenic genera in the postoperative period, particularly Streptococcus, has been linked to postoperative complications including anastomotic leak and surgical site infection. We hypothesized that the source of Streptococcus is the oral microbiome, and that fecal microbiota transplantation therapy (MTT) can repopulate beneficial genera and oppose the translocation of Streptococcus in the postoperative period.

Methods

This analysis was conducted in two phases: first, an exploratory cohort of 12 patients in whom fecal and saliva samples were analyzed surrounding resectional colon surgery (n=5) or colonoscopy (controls, n=7). Second, an interventional cohort of 12 patients who underwent colon resection for cancer or diverticular disease received microbiota transplant therapy (MTT) via orally-ingested formulation (IND 30860) and provided fecal samples for analysis. Samples were analyzed at up to six timepoints: pre-operative, within 24 hours of surgery (DOS), postoperative day (POD)10-14, POD30, POD90, and POD180. Microbial composition was assessed with 16S rRNA sequencing. Alpha and beta diversity was analyzed using mothur software. SourceTracker assessed the similarity of postoperative composition to donors as well as to patients’ own preoperative microbiota. Groups were compared using ANOVA, Kruskal-Wallis, and Spearman methods.

Results

In the exploratory cohort, microbial diversity, assessed by Shannon index, differed significantly between surgical and control patients on the day of procedure through POD10 in saliva samples (P = 0.003 and 0.05, respectively), and at POD10 in fecal samples (P = 0.022). Streptococcus was present in higher abundance in the saliva and stool of surgical patients compared to controls. Surgical fecal samples maintained increased similarity to saliva samples compared to controls on DOS, persisting through POD10 (P = 0.29 and 0.04, respectively, Figure 1AB). In the interventional cohort, immediately following surgery, samples had 8.8% similarity to donor, which rose to 81.1% by POD90 (Figure 1C). Following MTT, engraftment was significantly negatively correlated with Streptococcus abundance (-0.61; P<0.01). As Streptococcus abundance declined, a rise in commensal genera including Blautia and Faecalibacterium was noted (Figure 1D). Conclusions In this two-part exploration of shifts in microbiota following colorectal surgery, oral translocation of Streptococcus was effectively prevented by oral administration of MTT. Further evaluation of the immunologic reaction to these changes and correlation with clinical outcomes will be beneficial in the development of MTT as a therapeutic intervention surrounding colorectal surgery.