Exposure to the Harmful Algal Bloom (HAB) Toxin Microcystin-LR (MC-LR) Prolongs and Increases Severity of Dextran Sulfate Sodium (DSS)-Induced Colitis

Robin C Su,Fatimah K Khalaf,Caitlin E Baum,Deepak Malhotra,Apurva Lad,Shungang Zhang,Chrysan J Mohammed,Steven T Haller,Thomas M Blomquist,Andrew L Kleinhenz,Joshua D Breidenbach,Prabhatchandra Dube,David J Kennedy

doi:10.3390/toxins11060371

Abstract

Inflammatory Bowel Disease (IBD) represents a collection of gastrointestinal disorders resulting from genetic and environmental factors. Microcystin-leucine arginine (MC-LR) is a toxin produced by cyanobacteria during algal blooms and demonstrates bioaccumulation in the intestinal tract following ingestion. Little is known about the impact of MC-LR ingestion in individuals with IBD. In this study, we sought to investigate MC-LR’s effects in a dextran sulfate sodium (DSS)-induced colitis model. Mice were separated into four groups: (a) water only (control), (b) DSS followed by water (DSS), (c) water followed by MC-LR (MC-LR), and (d) DSS followed by MC-LR (DSS + MC-LR). DSS resulted in weight loss, splenomegaly, and severe colitis marked by transmural acute inflammation, ulceration, shortened colon length, and bloody stools. DSS + MC-LR mice experienced prolonged weight loss and bloody stools, increased ulceration of colonic mucosa, and shorter colon length as compared with DSS mice. DSS + MC-LR also resulted in greater increases in pro-inflammatory transcripts within colonic tissue (TNF-α, IL-1β, CD40, MCP-1) and the pro-fibrotic marker, PAI-1, as compared to DSS-only ingestion. These findings demonstrate that MC-LR exposure not only prolongs, but also worsens the severity of pre-existing colitis, strengthening evidence of MC-LR as an under-recognized environmental toxin in vulnerable populations, such as those with IBD.

Highlights

Inflammatory bowel disease (IBD) is a collection of disorders characterized by both acute and chronic inflammation of the gastrointestinal (GI) tract [1]
dextran sulfate sodium (DSS) + Microcystin-leucine arginine (MC-LR) mice were significantly lower than the control and MC-LR mice (p < 0.05)
To induce weight loss, splenomegaly, and severe colitis marked by transmural acute inflammation, ulceration, shortened colon length, and bloody stools

Summary

Introduction

Inflammatory bowel disease (IBD) is a collection of disorders characterized by both acute and chronic inflammation of the gastrointestinal (GI) tract [1]. Two of the most common forms of IBD are Crohn’s disease (CD) and ulcerative colitis (UC), which share certain characteristics and exhibit key differences. Hallmarks of CD are transmural acute and chronic inflammation, non-caseating granulomas, strictures, and fistulas, while UC is characterized by mucosal and submucosal acute inflammation, crypt abscesses, ulcerations, depletion of goblet cells and mucin, bloody diarrhea, and weight loss [1]. These two conditions are frequently accompanied by other comorbidities and complications, making overall clinical presentations complex, difficult to manage, financially burdensome, and symptomatically debilitating for affected individuals

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