{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:11:55Z","timestamp":1791807115463,"version":"4.3.4"},"reference-count":85,"publisher":"American Society for Clinical Investigation","issue":"1","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"content-version":"vor","delay-in-days":52,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 AI152477"],"award-info":[{"award-number":["R01 AI152477"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 AI124214"],"award-info":[{"award-number":["R01 AI124214"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["K23 AI163368"],"award-info":[{"award-number":["K23 AI163368"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,9]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>\n                      Fecal microbiota transplantation (FMT) is the most effective therapy for recurrent\n                      <jats:italic>Clostridioides difficile<\/jats:italic>\n                      infection (rCDI), yet its mechanism of action remains poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We report the results of a clinical trial of patients undergoing FMT therapy for rCDI (\n                      <jats:italic>n<\/jats:italic>\n                      = 16), which analyzed colon biopsies, plasma, PBMCs, and stool at the time of FMT and 2-month follow-up. Plasma and colon biopsy samples were also collected from healthy controls for comparison with patients with rCDI. Microbiome composition, colonic gene expression, and immune changes were evaluated through high-throughput sequencing and immunoprofiling via flow cytometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>No patients experienced recurrence at follow-up. FMT significantly altered the intestinal microbiome but had no significant impact on the systemic immune system. In contrast, FMT promoted broad changes in colonic transcriptional profiles compared with both pre-FMT and healthy control biopsies, inhibiting genes associated with proinflammatory signaling and upregulating type 2 immunity and proliferative pathways (Myc and mTORC1). FMT increased expression of IL-33 and the type 2 immune EGFR family ligand amphiregulin, potentially explaining upregulation of Myc and mTORC1 pathways. Spatial transcriptomics demonstrated that these changes were localized to the colonic epithelium. Comparison of transcriptional profiles with available single-cell gene sets determined that post-FMT biopsies were enriched in signatures associated with proliferative cell types while repressing signatures of differentiated colonocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>We conclude that FMT promotes proliferation of the colonic epithelium in patients with rCDI, which may drive regeneration and protect against subsequent CDI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>Clinicaltrials.gov NCT02797288.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>This work was funded by grants from the NIH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.195678","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T17:00:42Z","timestamp":1763485242000},"source":"Crossref","is-referenced-by-count":6,"title":["Fecal microbiota transplantation promotes type 2 mucosal immune responses with colonic epithelium proliferation in patients with recurrent Clostridioides difficile"],"prefix":"10.1172","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6032-4320","authenticated-orcid":true,"given":"G. 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