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Pulp Ameliorates Cyclophosphamide-Induced Intestinal Damage - Gut Microbiota and Co-Metabolites Regulation","","Polysaccharides modulate host health through interactions with gut microbiota and by reshaping the host–microbial metabolome, supporting immune regulation. This study assessed the Artocarpus heterophyllus Lam. (jackfruit) polysaccharide (JFP-Ps) against cyclophosphamide-induced immunosuppression in mice, emphasizing changes in gut microbiota composition and co-metabolite profiles. JFP-Ps increased beneficial bacteria such as Lactobacillus and Lachnospiraceae and reduced certain taxa including Akkermansia. Metabolomics demonstrated coordinated regulation of gut microbe-associated metabolites, notably short-chain fatty acids, amino acids, bile acids, and indoles, linked to multiple metabolic pathways. 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Pulp Ameliorates Cyclophosphamide-Induced Intestinal Damage by Regulating Gut Microbiota and Co-Metabolites  \nZhenyu He 1,2,†, Yunlong Li 1,2,†, Jun Yang 1, Chuan Li 1, Wei Wang 3, Yanjun Zhang 2,4,5, Huawei Chen 2,4,5, Jianjie Li 2,4,5, Jun Cao 1, * and Kexue Zhu 2,4,5, *  \nAcademic Editor: Annalisa Chiavaroli  \nReceived: 13 November 2025  \nRevised: 15 December 2025  \nAccepted: 28 December 2025  \nPublished: 2 January 2026  \nCopyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 School of Food Science and Engineering, Hainan University, Haikou 570228, China  \n2 Spice and Beverage Research Institute, Chinese Academy of Tropical Agricultural Sciences, Wanning 571533, China  \n3 School of Biological and Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou 310023, China  \n4 Key Laboratory of Processing Suitability and Quality Control of the Special Tropical Crops of Hainan Province, Wanning 571533, China  \n5 National Center of Important Tropical Crops Engineering and Technology Research, Wanning 571533, China  \n* [Correspondence: juncaoyd2007@126.com](Correspondence: juncaoyd2007@126.com) (J.C.); [zhukexue163@163.com](zhukexue163@163.com) (K.Z.)† The authors contributed equally to this work and share first authorship.  \nAbstract  \nBackground: Polysaccharides modulate host health by interacting with gut microbiota and reshaping the host–microbial metabolome, potentially facilitating immune regulation. Methods: This study evaluated the modulatory effect of Artocarpus heterophyllus Lam.(jackfruit) polysaccharide (JFP-Ps) against cyclophosphamide (Cy)-induced immunosuppression in mice, focusing on gut microbiota modulation and metabolite changes. Results: JFP-Ps effectively increased the beneficial bacteria ratio, such as Lactobacillus and Lachnospiraceae, while inhibiting some species like Akkermansia. Metabolomic analysis showed that JFP-Ps notably regulated gut microbe-associated metabolites, including short-chain fatty acids (SCFAs), amino acids, bile acids, indoles, and derivatives. These metabolites were involved in various metabolic pathways, including primary bile acid synthesis and biosynthesis of phenylalanine, tyrosine, and tryptophan, along with tryptophan catabolism, purine metabolic processes, and unsaturated fatty acid production. Additionally, significant correlations between microbial groups and functional metabolites were identified. Overall, JFP-Ps exerted an immuno-modulatory effect by reshaping gut microbiota and enhancing co-metabolism with the host. Conclusions: These results provided valuable insights into host–microbiota interactions and gut microbiota-targeted intervention strategies of tropical natural bioactive polysaccharides.  \nKeywords: Artocarpus heterophyllus Lam.; polysaccharide; gut microbiota; metabolomics; short-chain fatty acids  \n1. Introduction  \nThe human gastrointestinal tract harbors over 100 trillion microorganisms, encompassing bacteria, fungus, viruses, archaea, and protozoa [1] . Accumulating evidence underscores the pivotal role of gut microbiota in maintaining immune homeostasis and fostering overall well-being [2] . Importantly, the gut microbiota plays a critical role in regulating immune responses. Certain microorganisms can participate in the regulation  \nof specific subpopulations of immune cells. Conversely, a host’s immune status can alter the characteristics of the gut microbiota, such as its species composition, abundance, and distribution [3,4] . Nicholson et al. [2] described this host–microbiota metabolic cross-talk as a dynamic and reciprocal chemical signaling network, which integrates host physiological processes with the phylogenetic diversity and functionality of the gut microbiota. Metabolites serve as key mediators of the host–microbio","cbCaipeuJo9SCQwR","https://ap.wps.com/l/cbCaipeuJo9SCQwR","pdf",6348271,25,"English","# Abstract\n# Introduction","[{\"question\":\"What is the main aim of the study on JFP-Ps?\",\"answer\":\"To evaluate whether Artocarpus heterophyllus Lam. (jackfruit) polysaccharide can ameliorate cyclophosphamide-induced intestinal damage and immunosuppression by regulating gut microbiota and associated metabolites.\"},{\"question\":\"How does JFP-Ps affect gut microbiota in cyclophosphamide-treated mice?\",\"answer\":\"JFP-Ps increases the ratio of beneficial bacteria such as Lactobacillus and Lachnospiraceae while inhibiting some species including Akkermansia.\"},{\"question\":\"Which metabolite groups are regulated according to the metabolomic analysis?\",\"answer\":\"JFP-Ps notably regulates gut microbe-associated metabolites, including short-chain fatty acids, amino acids, bile acids, and indoles and their derivatives.\"}]","Polysaccharide from Artocarpus heterophyllus Lam. Pulp Ameliorates Cyclophosphamide-Induced Intestinal Damage - Gut Microbiota and Co-Metabolites Regulation | PDF",1790760679,63]