Integrating omics and network pharmacology reveals the anti-constipation role of chitosan with different molecular weights in constipated mice

Yuxuan Liang; Xiaoyi Wei; Jie Deng; Cheng Peng; Rui Ren; Yanying Luo; Jiexin Zhang; Xiaoqun Wei; Gary Hardiman; Yuanming Sun; Hong Wang

doi:10.1016/j.ijbiomac.2023.123930

Integrating omics and network pharmacology reveals the anti-constipation role of chitosan with different molecular weights in constipated mice

Int J Biol Macromol. 2023 Apr 30:235:123930. doi: 10.1016/j.ijbiomac.2023.123930. Epub 2023 Mar 6.

Authors

Yuxuan Liang¹, Xiaoyi Wei², Jie Deng², Cheng Peng³, Rui Ren², Yanying Luo², Jiexin Zhang², Xiaoqun Wei⁴, Gary Hardiman⁵, Yuanming Sun⁶, Hong Wang⁷

Affiliations

¹ Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou 510642, China. Electronic address: l402972616@163.com.
² Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou 510642, China.
³ Guangzhou Institute of Food Inspection, Guangzhou 510080, China.
⁴ Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou 510642, China. Electronic address: weixqun@scau.edu.cn.
⁵ The Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Belfast BT7 1NN, UK. Electronic address: G.Hardiman@qub.ac.uk.
⁶ Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China.
⁷ Guangdong Provincial Key Laboratory of Food Quality and Safety, College of Food Science, South China Agricultural University, Guangzhou 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China. Electronic address: gzwhongd@163.com.

PMID: 36889616
DOI: 10.1016/j.ijbiomac.2023.123930

Abstract

This study aimed to reveal the constipation-relieving role of chitosan (COS) with different molecular weights (1 kDa, 3 kDa and 244 kDa). Compared with COS3K (3 kDa) and COS240K (244 kDa), COS1K (1 kDa) more significantly accelerated gastrointestinal transit and defecation frequency. These differential effects were reflected in the regulation of specific gut microbiota (Desulfovibrio, Bacteroides, Parabacteroides and Anaerovorax) and short-chain fatty acids (propionic acid, butyric acid and valeric acid). RNA-sequencing found that the differential expressed genes (DEGs) caused by different molecular weights of COS were mainly enriched in intestinal immune-related pathways, especially cell adhesion molecules. Furthermore, network pharmacology revealed two candidate genes (Clu and Igf2), which can be regarded as the key molecules for the differential anti-constipation effects of COS with different molecular weights. These results were further verified by qPCR. In conclusion, our results provide a novel research strategy to help understand the differences in the anti-constipation effects of chitosan with different molecular weights.

Keywords: Chitosan; Constipation; Molecular weight; Network pharmacology; RNA-sequencing.

MeSH terms

Animals
Butyric Acid
Chitosan* / pharmacology
Constipation / metabolism
Mice
Molecular Weight
Network Pharmacology
Propionates / chemistry

Substances

Butyric Acid
Chitosan
Propionates