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

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

Yue Yang  1   2 , Cong Wen  3 , Shuilin Zheng  4 , Fengmei Song  1 , Ying Liu  1 , Xueqiong Yao  1 , Yan Tang  1 , Xiangling Feng  2 , Jihua Chen  2 , Fei Yang  1   2   5
Affiliations

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

Yue Yang et al. Toxins (Basel). .

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Effect of MC-LR on body weight. Data are presented as the mean ± SD.
Figure 2
Figure 2
Effect of MC-LR on histopathological changes. (A) CT treatment group; (B) 1 µg/L MC-LR treatment group; (C) 60 µg/L MC-LR treatment group; (D) 120 µg/L MC-LR treatment group. (E) Inflammation score. The red arrow indicates lymphocyte infiltration. Bar = 50 μm means original magnification 50×. *** p < 0.001 compared with CT group.
Figure 3
Figure 3
Effect of MC-LR on inflammatory factors. (A) The mRNA expression levels of IL-6; (B) the mRNA expression levels of IL-1β; (C) the mRNA expression levels of TNF-α; (D) the mRNA expression levels of IL-10. Data are presented as the mean ± SD; n = 5. * p < 0.05, ** p < 0.01, *** p < 0.001 compared with CT group.
Figure 4
Figure 4
Effect of MC-LR on CSF1R/Rap1b signaling pathway. (A) WB analysis of proteins (CSF1R and Rap1b). (B,C) Relative quantitation of protein level normalized to β-actin. Data are presented as the mean ± SD; n = 5. ** p < 0.01, *** p < 0.001 compared with CT group.
Figure 5
Figure 5
Effect of MC-LR on gut microbiome composition. (A) Representative phylum-level bacterial composition of the gut microbiome. (B) Representative genus-level bacterial composition of the gut microbiome. (C) The LDA score of the most differentially abundant taxa between CT and 120 µg/L MC-LR-treated groups as determined via LEfSe analysis. (D) Comparisons of the relative abundance of Lactobacillus between CT and MC-LR-treated groups. Data are presented as the mean ± SD; n = 5. ** p < 0.01 compared with CT group.
Figure 6
Figure 6
Effects of L. fermentum on CSF1R/Rap1b signaling pathway in MC-LR treatment cell model. (A) The mRNA expression levels of IL-6; (B) the mRNA expression levels of IL-1β; (C) the mRNA expression levels of TNF-α; (D) the mRNA expression levels of IL-10. Data are presented as the mean ± SD; n = 3. * p < 0.05, ** p < 0.01, *** p < 0.001 compared with CT group; ### p < 0.001 compared with MC-LR treatment group.
Figure 7
Figure 7
Effects of L. fermentum on inflammatory factors mRNA expression levels in MC-LR treatment cell model. (A) WB analysis of proteins (CSF1R and Rap1b). (B,C) Relative quantitation of protein level normalized to β-actin. Data are presented as the mean ± SD; n = 3. ** p < 0.01, *** p < 0.001 compared with CT group.
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