title: Targeting aberrant colon cancer-specific DNA methylation with lipoteichoic acid-deficient Lactobacillus acidophilus.
abstract: Pathogenic autoinflammatory responses triggered by dysregulated microbial interactions may lead to intestinal disorders and malignancies. Previously, we demonstrated that a lipoteichoic acid (LTA)-deficient Lactobacillus acidophilus strain, NCK2025, ameliorated inflammation-induced colitis, significantly reduced the number of polyps in a colonic polyposis cancer model and restored physiological homeostasis in both cases. Nonetheless, the regulatory signals delivered by NCK2025 to reprogram the gastrointestinal microenvironment, and thus resist colonic cancer progression, remain unknown. Accumulating evidence suggest that epigenetic changes, in the presence and absence of pathogenic inflammation, can result in colorectal cancer (CRC). To test possible epigenetic modifications induced by NCK2025, the expression of epigenetically regulated, CRC-associated genes was measured with and without bacterial treatment. In vivo and in vitro, NCK2025 enhanced the expression of tumor suppressor genes that may regulate CRC development. Therefore, differential epigenetic regulation of CRC-related genes by NCK2025 represents a potential therapy against colitis-associated and sporadic CRC.
authors.affiliation: Department of Infectious Diseases and Pathology, Division of Hepatology/Gastroenterology and Nutrition, Department of Medicine, Cancer Genetic Institute, University of Florida, Gainesville, FL, USA.
authors.forename: Yaíma L
authors.initials: YL
authors.lastname: Lightfoot
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Bikash
authors.initials: B
authors.lastname: Sahay
authors.forename: Mansour
authors.initials: M
authors.lastname: Mohamadzadeh
mesh_terms: D000818:Animals; D001691:Biological Therapy / Q000379:methods; D003110:Colonic Neoplasms / Q000473:pathology* / Q000628:therapy; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006801:Humans; D007779:Lactobacillus acidophilus / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000172:deficiency*; D013682:Teichoic Acids
chemical_list: D008070:Lipopolysaccharides; D013682:Teichoic Acids; C009900:lipoteichoic acid
keywords: DNA methylation; aberrant epigenetic alterations; colorectal cancer; inflammation; lipoteichoic acid