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However, its application in the gut\u2013islets axis and assessing regulators of endocrine hormone secretion has yet to be explored. Here, we developed an organ-on-a-chip platform featuring a microfluidic chip with scaffolds of a closed-packed porous structure to recapitulate the characteristics of the gut\u2013islets axis for bile acid (BA) evaluation. The scaffolds were fabricated by negative replication of assembled droplet templates, enabling intestinal L-cells and pancreatic \u03b2-cells to form uniform spheroids. The scaffolds were embedded within a well-designed cascading microfluidic chip capable of generating a concentration gradient. Through this, the assessment of different concentrations of BAs in promoting GLP-1 and insulin secretion was achieved, with results consistent with previous studies, indicating the high accuracy of our platform. This novel system holds promise for evaluating other drugs or signaling molecules involved in glucose homeostasis, offering a new avenue for metabolic drug discovery.<\/jats:p>","DOI":"10.34133\/research.0923","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T20:33:31Z","timestamp":1758141211000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":5,"title":["Organs-on-a-Chip Recapitulating the Gut\u2013Islets Axis for Endocrine Hormone Secretion Regulator Evaluation"],"prefix":"10.34133","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6536-6773","authenticated-orcid":false,"given":"Ji","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Zhongda Hospital, School of Medicine, \rSoutheast University, Nanjing 210009, China."},{"name":"Department of Rheumatology and Immunology, Institute of Translational Medicine, \rThe Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210002, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuhao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Institute of Translational Medicine, \rThe Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210002, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingbo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Zhongda Hospital, School of Medicine, \rSoutheast University, Nanjing 210009, China."},{"name":"Department of Rheumatology and Immunology, Institute of Translational Medicine, \rThe Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210002, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7458-9100","authenticated-orcid":true,"given":"Luoran","family":"Shang","sequence":"additional","affiliation":[{"name":"Zhongshan-Xuhui Hospital and the Shanghai Key Laboratory of Medical Epigenetics the International Co-laboratory of Medical Epigenetics and Metabolism Ministry of Science and Technology, \rInstitutes of Biomedical Sciences, Fudan University, Shanghai 200032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanjin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Institute of Translational Medicine, \rThe Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210002, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Zhongda Hospital, School of Medicine, \rSoutheast University, Nanjing 210009, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2025,10,9]]},"reference":[{"issue":"1","key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"6179","DOI":"10.1038\/s41467-023-41950-y","article-title":"Gut microbiota aggravates neutrophil extracellular traps-induced pancreatic injury in hypertriglyceridemic pancreatitis","volume":"14","author":"Li G","year":"2023","unstructured":"Li G, Liu L, Lu T, Sui Y, Zhang C, Wang Y, Zhang T, Xie Y, Xiao P, Zhao Z, et al. 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Lancet Diabetes Endocrinol. 2024;12(9):674\u2013680.","journal-title":"Lancet Diabetes Endocrinol"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.09.008"},{"issue":"4","key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.cmet.2020.11.017","article-title":"Hyocholic acid species improve glucose homeostasis through a distinct TGR5 and FXR signaling mechanism","volume":"33","author":"Zheng X","year":"2021","unstructured":"Zheng X, Chen T, Jiang R, Zhao A, Qing W, Kuang J, Sun D, Ren Z, Li M, Zhao M, et al. Hyocholic acid species improve glucose homeostasis through a distinct TGR5 and FXR signaling mechanism. 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