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Res."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ulcerative colitis (UC) is a chronic inflammatory bowel disease driven by dysregulated immune responses, particularly the aberrant activation of T helper 17 (Th17) cells. While microbiome-based therapies show promise, wild-type probiotics often lack specific mechanisms to target the metabolic and immunological drivers of inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, we engineered a cysteine-auxotrophic strain of\n                      <jats:italic>Bacteroides vulgatus<\/jats:italic>\n                      (BV1608) by chromosomally integrating the\n                      <jats:italic>E. coli cyuP<\/jats:italic>\n                      gene to enhance cysteine uptake. We evaluated its colonization capability, safety, and therapeutic efficacy in dextran sulfate sodium (DSS)-induced acute and chronic colitis murine models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>BV1608 exhibited superior colonization and cysteine assimilation compared to the wild-type strain. Oral administration of BV1608 significantly alleviated colitis symptoms, reduced pro-inflammatory cytokines, and restored intestinal barrier integrity. Mechanistically, BV1608 created a localized cysteine-restricted microenvironment in the gut and suppressed pathogenic Th17 differentiation. Under cystine-restricted conditions, ATF6 was activated in CD4\u207a T cells, and its inhibition partially restored IL-17A\u207a CD4\u207a T cell differentiation, indicating a functional role for ATF6. Meanwhile, cystine restriction was associated with increased BATF2 expression and enhanced ATF6 binding at the BATF2 promoter, suggesting BATF2 as a potential downstream node.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings demonstrate that metabolically engineered\n                      <jats:italic>B. vulgatus<\/jats:italic>\n                      BV1608 ameliorates colitis by coupling microbial cysteine sequestration with host immune modulation via the ATF6-dependent suppression of Th17 differentiation, while implicating BATF2-associated transcriptional regulation as a potential downstream mechanism. This study provides a novel synbiotic strategy for treating UC by targeting the immunometabolic interface.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00011-026-02341-3","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T11:19:46Z","timestamp":1788607186000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Depleting luminal cysteine with engineered bacteroides vulgatus alleviates experimental colitis by suppressing Th17 differentiation through an ATF6-dependent mechanism"],"prefix":"10.1007","volume":"75","author":[{"given":"Jianghao","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe-Xian","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanwen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace Y.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengyuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"issue":"7","key":"2341_CR1","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1038\/s41575-018-0003-z","volume":"15","author":"T Zuo","year":"2018","unstructured":"Zuo T, Kamm MA, Colombel JF, Ng SC. 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