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However, their widespread and clinical utility is severely limited by the poor viability of probiotics under harsh gastrointestinal conditions in the intestine. To address these challenges, a probiotic-based biohybrid (Lr@DGN) was bio-orthogonally fabricated by covalently anchoring the prebiotic \u03b2-glucan (GN) to the probiotic Limosilactobacillus reuteri (Lr). Upon oral administration, Lr@DGN colonized intestines with high survival rates, aided by gastrointestinal stress-shielding of GN, leading to immuno-enhancing effects through combining GN and live Lr. Consequently, in a Cy-induced immunosuppression mouse model, oral administration of Lr@DGN significantly mitigated body weight loss, restored the key immune organ indexes (thymus and spleen), ameliorated Cy-induced damage to the small intestine, enhanced the intestinal immune response, and elevated the serum levels of immunoglobulins IgG and IgA. By integrating the effects of a prebiotic shield and a live probiotic, this biohybrid system offers a promising and translatable approach for managing immunodeficiency and related disorders.<\/jats:p>","DOI":"10.3390\/foods15091540","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:43:51Z","timestamp":1777448631000},"page":"1540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prebiotic-Empowered Probiotics with Gastrointestinal Stress Resistance for Enhanced Oral Therapy of Immunosuppression"],"prefix":"10.3390","volume":"15","author":[{"given":"Xiaomin","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huangxin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Jiangxi Provincial Key Laboratory of Digestive Diseases, Department of Gastroenterology, Jiangxi Clinical Research Center for Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330066, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuwei","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianru","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9596-6163","authenticated-orcid":false,"given":"Yiqun","family":"Wan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9990-2359","authenticated-orcid":false,"given":"Hao","family":"Wan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102751","DOI":"10.1016\/j.ctrv.2024.102751","article-title":"Toxicity of immunotherapy combinations with chemotherapy across tumor indications: Current knowledge and practical recommendations","volume":"127","author":"Rached","year":"2024","journal-title":"Cancer Treat. 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