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Helminth infections are known to modulate host immunity and intestinal microbial composition; however, the therapeutic use of live parasites poses safety challenges. The recombinant Fasciola hepatica fatty acid-binding protein Fh15 is a helminth-derived molecule with anti-inflammatory effects in models of septic shock and dextran sulfate sodium (DSS)-induced colitis. Whether Fh15 also influences gut microbial composition during colitis remains unknown. Male C57BL\/6 mice received 4% DSS in drinking water for 7 days to induce colitis and were treated intraperitoneally with Fh15 (2 mg\/kg) on days 1, 3, and 5. Fecal samples were collected on days 2, 4, and 7 for 16S rRNA gene sequencing. Standard microbiota pipelines were used to evaluate community diversity. Acute DSS treatment disrupted gut microbial diversity and community structure compared with non-colitic controls. Fh15 treatment partially restored early microbial balance by shifting microbial composition toward that of healthy mice and reducing microbial dispersion, indicating enhanced community stability despite severe dysbiosis. Although alpha diversity did not return to control levels, Fh15 mitigated the expansion of pro-inflammatory genera (Enterococcus and Turicibacter) and preserved beneficial taxa, including Adlercreutzia.<\/jats:p>","DOI":"10.3390\/ijms27094068","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T01:12:09Z","timestamp":1777857129000},"page":"4068","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intermittent Administration of Helminth-Derived Fh15 Modulates Gut Microbiota and Partially Mitigates Dysbiosis in Early Stages of Severe Experimental Colitis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7565-0193","authenticated-orcid":false,"given":"Mar\u00eda Del Mar","family":"Figueroa-Gispert","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1538-7557","authenticated-orcid":false,"given":"Natalie M.","family":"Mel\u00e9ndez-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8456-2550","authenticated-orcid":false,"given":"Ana M.","family":"Espino","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1880-0498","authenticated-orcid":false,"given":"Filipa","family":"Godoy-Vitorino","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00936, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3748\/wjg.v7.i2.175","article-title":"Historical origins of current IBD concepts","volume":"7","author":"Kirsner","year":"2001","journal-title":"World J. 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