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Because the intestine is the first tissue exposed after ingestion, it is both a portal of systemic uptake and a direct toxicological target. This review integrates evidence on intestinal distribution and absorption, exposure\u2010dependent toxic phenotypes, and molecular mechanisms. Acute or high\u2010dose exposure predominantly causes villus erosion, epithelial apoptosis, cytoskeletal collapse, and rapid barrier failure, whereas repeated exposure at low or environmentally relevant doses produces low\u2010grade inflammation, fibrosis, microbiota and metabolite dysregulation, and increased susceptibility to colitis and colorectal tumor progression. Mechanistically, organic anion\u2010transporting polypeptide\u2010mediated uptake and inhibition of protein phosphatase 2A (PP2A) act as upstream events that promote protein hyperphosphorylation and interconnected oxidative stress, DNA damage, tight\u2010junction disassembly, inflammatory signaling, and dysregulated proliferation, apoptosis, migration, and invasion. Recent multiomics and fecal microbiota transplantation studies further support a bidirectional microbiota\u2010barrier\u2010immune axis in local and systemic effects. Quantitative interpretation nevertheless remains limited by heterogeneous dose metrics, short experiments, nonphysiological exposure routes, and scarce human longitudinal data. Future studies should prioritize environmentally realistic chronic and mixture exposures, human intestinal organoids and organ\u2010on\u2010chip systems, causal PP2A pathway perturbation, longitudinal biomonitoring, and harmonized benchmark\u2010dose analyses.<\/jats:p>","DOI":"10.1002\/jat.70416","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T23:06:43Z","timestamp":1787785603000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advances in the Intestinal Toxicity of Microcystin\u2010LR"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5210-2496","authenticated-orcid":false,"given":"Yichen","family":"Li","sequence":"first","affiliation":[{"name":"School of Nursing and Health Nanfang College Guangzhou  Guangzhou Guangdong 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