Claytor Jennifer D, Lin Din L, Magnaye Kevin M, Guerrero Yanedth Sanchez, Langelier Charles R, Lynch Susan V, El-Nachef Najwa
Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Immunology, University of California, San Francisco, CA, USA.
Dig Dis Sci. 2025 Mar;70(3):982-990. doi: 10.1007/s10620-024-08828-5. Epub 2025 Jan 13.
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.
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.
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.
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.
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.
在接受结肠切除术并进行回肠储袋肛管吻合术的溃疡性结肠炎（UC）患者中，储袋炎很常见。抗生素是治疗储袋炎症的一线疗法，这增加了肠道被多重耐药菌（MDRO）定植的可能性。粪便微生物移植（FMT）正在被研究用于治疗储袋炎和根除MDRO。先前使用需氧抗生素培养盘的研究表明，一些慢性储袋炎患者在接受FMT后可能恢复对氟喹诺酮的敏感性。然而，肠道MDRO包括厌氧、苛求菌，使用传统方法很难培养。
我们旨在评估FMT是否能降低慢性储袋炎患者抗生素耐药基因（ARG）的丰度，或影响耐药组的多样性、均匀度或丰富度。
我们收集了18例先前参与一项观察性研究（该研究将FMT作为储袋炎的一种治疗方法进行调查）患者的感染和抗生素暴露相关临床特征。使用FLASH（通过杂交发现低丰度序列）对26份FMT前后的粪便样本进行分析，这是一种基于CRISPR/Cas9的鸟枪法宏基因组序列富集技术，可检测获得性和染色体细菌ARG。采用Wilcoxon秩和检验评估FMT前后临床特征、ARG计数、耐药组多样性和ARG丰富度的差异。
所有13例有足够粪便样本进行分析的患者在单次内镜FMT之前最近都因储袋炎接受了抗生素治疗。所有患者的粪便微生物群在基线时都有多重耐药基因和超广谱β-内酰胺酶耐药基因的证据；62%编码氟喹诺酮耐药基因。FMT后总体ARG计数有数值上的下降，但未观察到统计学上的显著差异（P = 0.19）。丰富度和多样性没有显著改变。3例患者在5年随访期内发生感染，均与MDRO无关。
抗生素耐药基因在接触过抗生素的慢性储袋炎患者中普遍存在。FMT导致ARG在数值上下降，但无统计学显著变化，ARG的多样性、丰富度或均匀度也无显著变化。有必要进一步研究以改善FMT植入并优化炎症性储袋疾病患者的FMT给药方式。
