Background
Pouchitis is common among patients with ulcerative colitis who have had colectomy with J-pouch creation. Frequent antibiotic courses are first-line treatment for pouchitis, which increases the potential for gut colonization with multi-drug resistant organisms (MDRO). Fecal microbial transplant (FMT) is being studied in the treatment of pouchitis and in the eradication of MDRO in vulnerable populations. A previous case series using antibiotic resistance discs in culture suggested 2 of 4 patients with pouchitis regained Ciprofloxacin sensitivity after FMT. However, gut MDRO include anaerobic, fastidious organisms that are difficult to culture using traditional methods.

Aim
We aimed to assess whether FMT changed the abundance of antibiotic resistance genes (ARG) or resistome diversity of patients with chronic pouchitis in a descriptive, pilot study using previously collected samples.

Methods
We collected clinical characteristics regarding infections and antibiotic exposures for 18 previously enrolled patients with chronic pouchitis, 13 of whom provided 26 stool samples (pre- and post-FMT) of suitable quantity for analysis. We used FLASH (Finding Low Abundance Sequences by Hybridization), a novel CRISPR/Cas9-based sequence enrichment technique that detects acquired resistance and chromosomal bacterial ARGs, to assess differences in pre- and post-FMT resistome diversity and ARG counts.

Results
All 13 of the patients with sufficient stool samples for analysis had recently received antibiotics for pouchitis prior to a single endoscopic FMT. All patients had multi-drug resistance genes and ESBL resistance genes at baseline; 62% had fluoroquinolone resistance genes. FMT did not alter resistome diversity or significantly reduce ARG counts, although there was a trend towards lower overall ARG counts after FMT (p=0.09). Three patients developed infections during 5-year follow-up, none of them with MDRO.

Conclusion
Antibiotic resistance genes are prevalent among antibiotic-exposed patients with chronic pouchitis. FMT did not significantly improve the diveristy or burden of ARG colonization in patient with chronic pouchitis. Further investigations to improve FMT engraftment and to optimize FMT delivery in patients with inflammatory pouch disorders are warranted.

Figure 1. Pre- and post-FMT resistomes were not cluster-separated.

Figure 2. No significant changes in resistome diversity were noted after FMT.

Susan Lynch

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