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Medicinal plant polysaccharides (MPPs) are structurally diverse macromolecules that often resist host digestion and undergo microbial transformation in the colon, but their effects cannot be interpreted as those of a homogeneous intervention class. In this structured narrative review, we critically synthesize evidence across structural carbohydrate biology, microbial ecology, metabolite signaling, and immune aging and propose a structure\u2013microbiota\u2013metabolite\u2013immunity framework for evaluating how MPPs may influence immunosenescence. Monosaccharide composition, glycosidic linkages, molecular-weight distribution, branching, uronic acid content, chemical substitutions, and higher-order conformation can shape microbial carbohydrate-active enzyme activity, polysaccharide utilization, and ecological cross-feeding. The resulting changes in short-chain fatty acids, secondary bile acids, tryptophan-derived indoles, and other metabolites may affect epithelial barrier integrity, regulatory T-cell\/T helper 17-cell (Treg\/Th17) balance, macrophage polarization, nuclear factor-\u03baB (NF-\u03baB) signaling, NLR family pyrin domain-containing 3 (NLRP3) inflammasome activation, and systemic inflammatory tone. However, evidence from in vitro systems and young disease models primarily supports mechanistic plausibility and should not be treated as direct evidence of immunosenescence modification. Translation will require structurally defined preparations, causal validation in aging-relevant models, comparison with established fermentable fibers, identification of responder phenotypes, and adequately powered trials in older adults.<\/jats:p>","DOI":"10.3390\/nu18162641","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T16:17:52Z","timestamp":1786551472000},"page":"2641","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Medicinal Plant Polysaccharides as Microbiota-Directed Modulators of Immunosenescence: Structural Determinants, Metabolite Reprogramming, and Host Immune Regulation"],"prefix":"10.3390","volume":"18","author":[{"given":"Kailang","family":"Mu","sequence":"first","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meihui","family":"He","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqi","family":"Liao","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changliu","family":"Shao","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingxuan","family":"Xie","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junli","family":"Xie","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6377-7317","authenticated-orcid":false,"given":"Zhigang","family":"Ju","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"},{"name":"College of Pharmacy, Guangdong Medical University, Dongguan 523808, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Zhong","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"College of Life Sciences and Biopharmaceuticals, Guangdong Medical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Pang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang 550025, China"},{"name":"College of Pharmacy, Guangdong Medical University, Dongguan 523808, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2026, June 10). 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