Lactobacillus fermentum Alleviates the Colorectal Inflammation Induced by Low-Dose Sub-Chronic Microcystin-LR Exposure

Yue Yang; Cong Wen; Shuilin Zheng; Fengmei Song; Ying Liu; Xueqiong Yao; Yan Tang; Xiangling Feng; Jihua Chen; Fei Yang

doi:10.3390/toxins15090579

Lactobacillus fermentum Alleviates the Colorectal Inflammation Induced by Low-Dose Sub-Chronic Microcystin-LR Exposure

Toxins (Basel). 2023 Sep 19;15(9):579. doi: 10.3390/toxins15090579.

Authors

Yue Yang^{1

2}, Cong Wen³, Shuilin Zheng⁴, Fengmei Song¹, Ying Liu¹, Xueqiong Yao¹, Yan Tang¹, Xiangling Feng², Jihua Chen², Fei Yang^{1

2

5}

Affiliations

¹ The Key Laboratory of Typical Environmental Pollution and Health Hazards of Hunan Province, Department of Epidemiology and Health Statistics, School of Public Health, Hengyang Medical School, University of South China, Hengyang 421001, China.
² Hunan Provincial Key Laboratory of Clinical Epidemiology, Xiangya School of Public Health, Central South University, Changsha 410017, China.
³ Changsha Yuhua District Center for Disease Control and Prevention, Changsha 410014, China.
⁴ Changsha Center for Disease Control and Prevention, Changsha 410004, China.
⁵ Hengyang Medical School, The First Affiliated Hospital, University of South China, Hengyang 421001, China.

Abstract

Microcystin-LR (MC-LR) contamination is a worldwide environmental problem that poses a grave threat to the water ecosystem and public health. Exposure to MC-LR has been associated with the development of intestinal injury, but there are no effective treatments for MC-LR-induced intestinal disease. Probiotics are "live microorganisms that are beneficial to the health of the host when administered in sufficient quantities". It has been demonstrated that probiotics can prevent or treat a variety of human diseases; however, their ability to mitigate MC-LR-induced intestinal harm has not yet been investigated. The objective of this study was to determine whether probiotics can mitigate MC-LR-induced intestinal toxicity and its underlying mechanisms. We first evaluated the pathological changes in colorectal tissues using an animal model with sub-chronic exposure to low-dose MC-LR, HE staining to assess colorectal histopathologic changes, qPCR to detect the expression levels of inflammatory factors in colorectal tissues, and WB to detect the alterations on CSF1R signaling pathway proteins in colorectal tissues. Microbial sequencing analysis and screening of fecal microorganisms differential to MC-LR treatment in mice. To investigate the role of microorganisms in MC-LR-induced colorectal injury, an in vitro model of MC-LR co-treatment with microorganisms was developed. Our findings demonstrated that MC-LR treatment induced an inflammatory response in mouse colorectal tissues, promoted the expression of inflammatory factors, activated the CSF1R signaling pathway, and significantly decreased the abundance of Lactobacillus. In a model of co-treatment with MC-LR and Lactobacillus fermentum (L. fermentum), it was discovered that L. fermentum substantially reduced the incidence of the colorectal inflammatory response induced by MC-LR and inhibited the protein expression of the CSF1R signaling pathway. This is the first study to suggest that L. fermentum inhibits the CSF1R signaling pathway to reduce the incidence of MC-LR-induced colorectal inflammation. This research may provide an excellent experimental foundation for the development of strategies for the prevention and treatment of intestinal diseases in MC-LR.

Keywords: Lactobacillus fermentum; colorectal inflammation; intestinal diseases; microcystin-LR; probiotics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Colorectal Neoplasms*
Ecosystem
Humans
Inflammation / chemically induced
Limosilactobacillus fermentum*
Mice

Substances

cyanoginosin LR

Grants and funding

The work was supported by the Key Research and Development Projects in Hunan Province (2022SK2089) and the Huxiang Youth Talent Program (2021RC3107).