Microcystin-LR Induces and Aggravates Colitis through NLRP3 Inflammasome-Mediated Pyroptosis in Mice

Abstract

Inflammatory bowel disease (IBD) is a chronic, lifelong gastrointestinal disease, characterized by periods of activity and remission. The etiology of IBD is closely related to environmental factors. Previous studies have shown that the cyanotoxin microcystin-LR (MC-LR) causes intestinal damage, even IBD. To explore MC-LR’s effects and potential mechanisms on IBD occurrence and development, we used dextran-sulfate sodium gavage (DSS) and MC-LR together for the first time in mice. There were four groups of mice: (A) mice given PBS gavage (control, CT); (B) mice given 3% DSS gavage (DSS); (C) mice given 200 µg/kg MC-LR gavage (MC-LR); and (D) mice given 3% DSS + 200 µg/kg MC-LR gavage (DSS + MC-LR). Compared with the CT group, the MC-LR group and the DSS group demonstrated more severe colitis results, which presented as higher weight loss, an increased Disease Activity Index (DAI) score, shorter colon length, a higher degree of tissue structural damage, more apoptotic cells, and greater pro-inflammatory cytokines. Similarly, the DSS + MC-LR group showed more severe colitis compared with the DSS group. Subsequent experiments confirmed that MC-LR or DSS increased the expression of pyroptosis-related proteins mediated by the nucleotide-binding domain-like receptor protein 3 (NLRP3). Likewise, compared with the DSS group, the DSS + MC-LR group expressed these proteins at a higher level. In conclusion, our research is the first to show that MC-LR may induce colitis, and even IBD, through NLRP3 inflammasome-mediated pyroptosis, and it could aggravate DSS-induced colitis in the same way.

A Case Series of Potential Pediatric Cyanotoxin Exposures Associated with Harmful Algal Blooms in Northwest Ohio

“…The prevalence and persistence of CyanoHABs are increasing globally, raising the likelihood that more people will be at risk for cyanotoxin exposure and illness. Additionally, work from our lab has shown that several common comorbidities affecting the liver (nonalcoholic fatty liver disease, or NAFLD) [26][27][28][29], gut (colitis/irritable bowel disease or IBD) [30,31], and airways (asthma) [14] may increase susceptibility to cyanotoxins such as microcystin. These conditions are notable as they are already increasingly common As the incidence and prevalence of diseases such as non-alcoholic fatty liver disease, inflammatory bowel disease, and asthma increase, this may have profound impacts on the health of at-risk populations who are exposed to CyanoHABs.…”

Serum Microcystin-LR Levels Linked with Risk of Inflammatory Bowel Disease: A Matched Case-Control Study in China

“…For example, our previous work identified MC-LR as an independent factor in inducing intestinal damage in vitro and acute toxic animal models. 25,26 In addition, our recent study showed that MC-LR regulates the release of inflammatory factors and fibrosis markers through the CSF1R/ Rap1b signaling pathway in a mouse model, leading to chronic colorectal inflammation, fibrosis, and barrier disruption. The intestinal flora of mice exposed to MC-LR was altered, with an increase in Turicibacter and Clostridium and a decrease in Ruminococcus and Alloprevotella.…”