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Effect of Fecal Microbiota Transplant on Antibiotic Resistance Genes Among Patients with Chronic Pouchitis
Jennifer D Claytor1, Din L Lin2, Kevin M Magnaye2,3
1Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. jennifer.claytor@mountsinai.org.
Background:
Pouchitis is common among patients with ulcerative colitis (UC) who have had colectomy with ileal pouch-anal anastomosis. Antibiotics are first-line therapy for pouch inflammation, increasing 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. Prior work using aerobic antibiotic culture disks suggests that some patients with chronic pouchitis may regain fluoroquinolone 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 reduced the abundance of antibiotic resistance genes (ARG) or affected resistome diversity, evenness, or richness in patients with chronic pouchitis.
Methods:
We collected clinical characteristics regarding infections and antibiotic exposures for 18 patients who had previously been enrolled in an observational study investigating FMT as a treatment for pouchitis. Twenty-six pre- and post-FMT stool samples were analyzed using FLASH (Finding Low Abundance Sequences by Hybridization), a CRISPR/Cas9-based shotgun metagenomic sequence enrichment technique that detects acquired and chromosomal bacterial ARGs. Wilcoxon rank sum tests were used to assess differences in clinical characteristics, ARG counts, resistome diversity and ARG richness, pre- and post-FMT.
Results:
All 13 of the patients with sufficient stool samples for analysis had recently received antibiotics for pouchitis prior to a single endoscopic FMT. Fecal microbiomes of all patients had evidence of multi-drug resistance genes and ESBL resistance genes at baseline; 62% encoded fluoroquinolone resistance genes. A numerical decrease in overall ARG counts was noted post-FMT, but no statistically significant differences were noted (P = 0.19). Richness and diversity were not significantly altered. Three patients developed infections during the 5-year follow-up period, none of which were associated with MDRO.
Conclusion:
Antibiotic resistance genes are prevalent among antibiotic-exposed patients with chronic pouchitis. FMT led to a numerical decrease, but no statistically significant change in ARG, nor were there significant changes in the diversity, richness, or evenness of ARGs. Further investigations to improve FMT engraftment and to optimize FMT delivery in patients with inflammatory pouch disorders are warranted.
Insights
Fecal microbial transplant (FMT) numerically decreased antibiotic resistance genes (ARGs) in patients with chronic pouchitis, but did not significantly alter their abundance, diversity, or richness. Further research is needed to optimize FMT for inflammatory pouch disorders.
Area of Science:
- Gastroenterology
- Microbiome Research
- Infectious Disease
Background:
- Pouchitis is a common complication of ulcerative colitis surgery, often treated with antibiotics.
- Antibiotic use increases the risk of multi-drug resistant organisms (MDRO) in the gut.
- Fecal microbial transplant (FMT) is being investigated for pouchitis and MDRO eradication.
Purpose of the Study:
- To evaluate if FMT reduces antibiotic resistance genes (ARGs) in chronic pouchitis patients.
- To assess the impact of FMT on resistome diversity, evenness, and richness.
Main Methods:
- Analyzed pre- and post-FMT stool samples from 18 patients using a CRISPR/Cas9-based shotgun metagenomic sequencing technique (FLASH).
- Collected clinical data on infections and antibiotic exposure.
- Used Wilcoxon rank sum tests to compare ARG counts, diversity, and richness before and after FMT.
Main Results:
- All patients had baseline MDRO and ESBL resistance genes; 62% had fluoroquinolone resistance genes.
- A numerical decrease in overall ARG counts was observed post-FMT, but not statistically significant (P=0.19).
- No significant changes in ARG richness or diversity were detected; no MDRO infections occurred during follow-up.
Conclusions:
- Antibiotic resistance genes are common in antibiotic-exposed chronic pouchitis patients.
- FMT resulted in a non-significant numerical decrease in ARGs and did not alter resistome diversity or richness.
- Optimizing FMT engraftment and delivery is crucial for inflammatory pouch disorders.
