{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:49:38Z","timestamp":1792162178221,"version":"4.4.0"},"reference-count":61,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M753455"],"award-info":[{"award-number":["2024M753455"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hubei Jiangxia Laboratory Open Foundation","award":["2025JXKF023"],"award-info":[{"award-number":["2025JXKF023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Inflammatory bowel disease (IBD) is a complex intestinal disorder for which effective treatment options remain limited. The modulation of gut microbiota balance using probiotics holds promise as a therapeutic approach to restore intestinal microenvironment homeostasis. However, the clinical translation of conventional probiotics is constrained by the suboptimal therapeutic efficacy. Here, we constructed a recombinant Escherichia coli Nissle 1917 strain (EcN-CR-IL2) based on an optimized calprotectin-responsive ykgMO promoter to achieve inflammation-dependent expression of the immunomodulatory cytokine interleukin-2 (IL-2), which selectively expands regulatory T cells to suppress aberrant intestinal inflammation. The optimized promoter achieved approximately 100-fold greater induction than the native ykgMO promoter and responded robustly to calprotectin both in vitro and in a DSS-induced murine colitis model in vivo. Oral administration of EcN-CR-IL2 significantly alleviated colitis symptoms in both prophylactic and therapeutic settings, suppressed proinflammatory cytokine levels, restored intestinal barrier integrity, and shifted gut microbiota composition toward a more homeostatic profile. Importantly, the therapeutic output of EcN-CR-IL2 correlated with local calprotectin levels, enabling on-demand modulation of anti-inflammatory effects in response to disease progression. This study presents a probiotic delivery system that combines real-time sensing of a clinically validated biomarker with autonomous therapeutic production, providing a new approach for the treatment of chronic intestinal inflammatory diseases.<\/jats:p>","DOI":"10.1021\/acssynbio.6c00347","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:03:27Z","timestamp":1790355807000},"page":"4145-4156","source":"Crossref","is-referenced-by-count":0,"title":["Engineered Calprotectin-Responsive Probiotics for Inflammatory Bowel Disease Treatment"],"prefix":"10.1021","volume":"15","author":[{"given":"Fan","family":"Yang","sequence":"first","affiliation":[{"name":"Chinese Academy of Sciences , , , ,","place":["Wuhan, Hubei, China, 430071"]},{"name":"University of Chinese Academy of Sciences , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"He","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , , ,","place":["Wuhan, Hubei, China, 430071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Lin","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , , ,","place":["Wuhan, Hubei, China, 430071"]},{"name":"Hubei Jiangxia Laboratory , ,","place":["Wuhan, China, 430200"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xindi","family":"Huang","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , , ,","place":["Wuhan, Hubei, China, 430071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuefeng","family":"Hu","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , , ,","place":["Wuhan, Hubei, China, 430071"]},{"name":"University of Chinese Academy of Sciences , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , , ,","place":["Wuhan, Hubei, China, 430071"]},{"name":"University of Chinese Academy of Sciences , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Wu","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , , ,","place":["Wuhan, Hubei, China, 430071"]},{"name":"University of Chinese Academy of Sciences , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayang","family":"Xi","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , , ,","place":["Wuhan, Hubei, China, 430071"]},{"name":"University of Chinese Academy of Sciences , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Lu","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , , ,","place":["Wuhan, Hubei, China, 430071"]},{"name":"University of Chinese Academy of Sciences , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengke","family":"Li","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , , ,","place":["Wuhan, Hubei, China, 430071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6153-1348","authenticated-orcid":true,"given":"Yangbo","family":"Hu","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , , ,","place":["Wuhan, Hubei, China, 430071"]},{"name":"Hubei Jiangxia Laboratory , ,","place":["Wuhan, China, 430200"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"issue":"1","key":"2026101610065029400_cit1","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1186\/s12951-025-03466-z","article-title":"Coptis chinensis-derived extracellular vesicle-like nanoparticles delivered miRNA-5106 suppresses NETs by restoring zinc homeostasis to alleviate colitis","volume":"23","author":"Yang","year":"2025","journal-title":"J. Nanobiotechnol."},{"issue":"1","key":"2026101610065029400_cit2","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1038\/s41419-021-03395-3","article-title":"The role of the Hippo pathway in the pathogenesis of inflammatory bowel disease","volume":"12","author":"Xie","year":"2021","journal-title":"Cell Death Dis."},{"issue":"1","key":"2026101610065029400_cit3","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adz9069","article-title":"Bacteriocin-transport-inspired oral peptide-probiotic delivery ameliorates IBD complications via autophagy and gut homeostasis","volume":"12","author":"Yu","year":"2026","journal-title":"Sci. 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