Unraveling the gut microbiota and short-chain fatty acids characteristics and associations in a cancer cachexia mouse model

Hao Liu; Yuxi Cheng; Yidan Qu; Guohao Wu

doi:10.1016/j.micpath.2023.106332

Unraveling the gut microbiota and short-chain fatty acids characteristics and associations in a cancer cachexia mouse model

Microb Pathog. 2023 Oct:183:106332. doi: 10.1016/j.micpath.2023.106332. Epub 2023 Sep 4.

Authors

Hao Liu¹, Yuxi Cheng¹, Yidan Qu², Guohao Wu³

Affiliations

¹ Department of General Surgery/Shanghai Clinical Nutrition Research Center, Zhongshan Hospital, Fudan University, Shanghai, China.
² Department of Medicine, Shandong First Medical University (Shandong Academy of Medical Sciences) of China, Jinan, Shandong, China; Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong, China.
³ Department of General Surgery/Shanghai Clinical Nutrition Research Center, Zhongshan Hospital, Fudan University, Shanghai, China. Electronic address: dr_wugh@163.com.

PMID: 37673351
DOI: 10.1016/j.micpath.2023.106332

Abstract

Objective: Cachexia is a common pathological condition in cancer patients, affecting prognosis and treatment outcomes. The relationship between cachexia and gut microbiota and short-chain fatty acids (SCFAs) remains understudied. This research aimed to establish a cachexia mouse model and explore the gut microbiota-SCFAs connection. The study provides fundamental insights into the regulatory mechanisms of cancer cachexia and potential therapeutic strategies.

Methods: A cachexia mouse model was created using C26 cells, with relevant indicators measured. Histological and immunohistochemical analyses assessed muscle structure and protein expression. ELISA was performed to detect the levels of IL-1β, IL-6, TNF-α, and LPS in serum to evaluate inflammation.16S rDNA sequencing and GC-MS quantified gut microbiota and SCFAs. Bioinformatics analysis identified indicator species and explored microbiota-SCFAs correlations.ROC analysis was performed to assess the potential of gut microbiota and SCFAs in identifying cachexia.

Results: The cachexia mouse model exhibited weight loss, muscle atrophy, and elevated inflammatory factors. Gut microbiota in cachexia mice showed decreased diversity and imbalance. Fourteen bacterial genera were identified as potential cachexia indicators. Functional prediction indicated alterations in the functional composition of gut microbial communities in cachexia mice, particularly in carbohydrate and lipid metabolism pathways. Four SCFAs showed significant changes, potentially serving as diagnostic factors. Specific microbial taxa were positively or negatively correlated with changes in SCFAs, and these microbial taxa and differential SCFAs were also correlated with inflammatory cytokines.

Conclusion: Our study uncovers the gut microbiota and SCFAs features in a cachexia mouse model, revealing novel correlations between them. These newfound insights into the interplay between cachexia, gut microbiota, and SCFAs provide a crucial foundation for understanding the mechanisms behind cancer cachexia development and potential therapeutic approaches.

Keywords: Cachexia; Gut microbiota; Metabolites; Microbiota; Short-chain fatty acids.

MeSH terms

Animals
Cachexia
Disease Models, Animal
Fatty Acids, Volatile
Gastrointestinal Microbiome*
Mice
Microbiota*
Neoplasms*

Substances

Fatty Acids, Volatile