{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:50:31Z","timestamp":1791589831382,"version":"4.3.4"},"reference-count":46,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32472348"],"award-info":[{"award-number":["32472348"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key-Area Research and Development Program of Guangdong Province","award":["2022B1111070006"],"award-info":[{"award-number":["2022B1111070006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Functional constipation (FC) represents a highly prevalent gastrointestinal disorder, affecting approximately 8.5% of the population in China. It is frequently associated with anxiety and depression, significantly impairing patients\u2019 quality of life. Conventional microecological therapeutic approaches predominantly rely on empirical probiotic\u2013prebiotic combinations. However, these pairings are seldom selected based on strain-specific metabolic characteristics, ultimately leading to suboptimal therapeutic synergy. Methods: The generation time (GT) of four constipation-relief strains was measured across eight oligosaccharides to identify optimal substrates for synbiotic formulation. The GT-optimized synbiotic was verified in a loperamide-induced mouse model vs. single probiotics\/prebiotics. The related mechanisms of were assessed through 16S rDNA sequencing, targeted metabolomics, and qPCR. Results: The GT-optimized synbiotic significantly outperformed all single components. Specifically, the synbiotic significantly decreased the time to first black stool and increased fecal water content. Mechanistically, it restored colonic neurotransmitter balance, suppressed aquaporin expression, enriched butyrate-producing bacteria, and repaired barrier integrity. Overall, these effects work together, increasing the moisture content of the feces and accelerating intestinal peristalsis, ultimately alleviating constipation. Conclusions: We propose a GT-guided precision-pairing strategy that identifies optimal prebiotics based on strain-specific generation times, demonstrating synergistic enhancement of short-chain fatty acid (SCFA) production, enteric neurotransmitter signaling, and aquaporin-mediated water transport. This GT guided synbiotic approach shows promise in preclinical models and warrants validation in human trials.<\/jats:p>","DOI":"10.3390\/nu18020184","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T11:13:18Z","timestamp":1767697998000},"page":"184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Efficacy and Mechanism of Synbiotics in Relieving Functional Constipation: Optimized by Generation Time"],"prefix":"10.3390","volume":"18","author":[{"given":"Linlin","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"Wuxi Institute for Specialized Nutrition and Health Co., Ltd., Wuxi 214142, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huahao","family":"Cai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"Wuxi Institute for Specialized Nutrition and Health Co., Ltd., Wuxi 214142, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingwei","family":"Yao","sequence":"additional","affiliation":[{"name":"Wuxi Institute for Specialized Nutrition and Health Co., Ltd., Wuxi 214142, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehua","family":"Chen","sequence":"additional","affiliation":[{"name":"Infinitus (China) Company Ltd., Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhi","family":"Li","sequence":"additional","affiliation":[{"name":"Infinitus (China) Company Ltd., Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cencen","family":"Liu","sequence":"additional","affiliation":[{"name":"Infinitus (China) Company Ltd., Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shumao","family":"Cui","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China"},{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"},{"name":"Wuxi Institute for Specialized Nutrition and Health Co., Ltd., Wuxi 214142, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Chen, Z., Peng, Y., Shi, Q., Chen, Y., Cao, L., Jia, J., Liu, C., and Zhang, J. 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