# Polysaccharide from Artocarpus heterophyllus Lam. Pulp Ameliorates Cyclophosphamide-Induced Intestinal Damage by Regulating Gut Microbiota and Co-Metabolites

## TL;DR

A jackfruit polysaccharide helps reduce intestinal damage from a chemotherapy drug by changing gut bacteria and their metabolites.

## Contribution

This study reveals how a tropical fruit polysaccharide modulates gut microbiota and co-metabolites to ameliorate chemotherapy-induced intestinal damage.

## Key findings

- JFP-Ps increased beneficial gut bacteria like Lactobacillus and Lachnospiraceae while inhibiting Akkermansia.
- The polysaccharide regulated metabolites such as SCFAs, amino acids, and bile acids involved in key metabolic pathways.
- JFP-Ps reshaped gut microbiota and co-metabolism, leading to immuno-modulatory effects in mice.

## Abstract

Background: 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.