Journal Article

Melatonin controls microbiota in colitis by goblet cell differentiation and antimicrobial peptide production through Toll-like receptor 4 signalling

Son, Mijeong, Park, Young Sook, Kim, Soochan, Cheon, Jae Hee, Kim, Seung Won

2020

Overview

Microbial dysbiosis has long been postulated to be associated with the pathogenesis of inflammatory bowel disease (IBD). Although evidence supporting the anti-colitic effects of melatonin have been accumulating, it is not clear how melatonin affects the microbiota. Herein, we investigated the effects of melatonin on the microbiome in colitis and identified involvement of Toll-like receptor (TLR) 4 signalling in the effects. Melatonin improved dextran sulfate sodium (DSS)-induced colitis and reverted microbial dysbiosis in wild-type (WT) mice but not in TLR4 knockout (KO) mice. Induction of goblet cells was observed with melatonin administration, which was accompanied by suppression of Il1b and Il17a and induction of melatonin receptor and Reg3β, an antimicrobial peptide (AMP) against Gram-negative bacteria. In vitro , melatonin treatment of HT-29 intestinal epithelial cells promotes mucin and wound healing and inhibits growth of Escherichia coli . Herein, we showed that melatonin significantly increases goblet cells, Reg3β, and the ratio of Firmicutes to Bacteriodetes by suppressing Gram-negative bacteria through TLR4 signalling. Our study suggests that sensing of bacteria through TLR4 and regulation of bacteria through altered goblet cells and AMPs is involved in the anti-colitic effects of melatonin. Melatonin may have use in therapeutics for IBD.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13/1 / 13/51 / 14/1 / 14/19 / 14/63 / 64/60 / 692/4020/1503/257 / 692/4020/1503/2745 / Animals / Antimicrobial agents / Antimicrobial peptides / Bacteria / Bacteroidetes - drug effects / Bacteroidetes - immunology / Bacteroidetes - isolation & purification / Cell differentiation / Cell Differentiation - drug effects / Colitis / Colitis, Ulcerative - chemically induced / Colitis, Ulcerative - drug therapy / Colitis, Ulcerative - immunology / Colitis, Ulcerative - microbiology / Colon / Dextran / Dextran sulfate / Dextran Sulfate - toxicity / Disease Models, Animal / Dysbacteriosis / Dysbiosis - drug therapy / Dysbiosis - immunology / Dysbiosis - microbiology / Dysbiosis - pathology / E coli / Epithelial cells / Firmicutes - drug effects / Firmicutes - immunology / Firmicutes - isolation & purification / Gastrointestinal Microbiome - drug effects / Gastrointestinal Microbiome - immunology / Goblet cells / Goblet Cells - drug effects / Goblet Cells - immunology / Goblet Cells - microbiology / Goblet Cells - physiology / Gram-negative bacteria / HT29 Cells / Humanities and Social Sciences / Humans / Inflammatory bowel disease / Inflammatory bowel diseases / Interleukin 1 / Intestine / Male / Melatonin / Melatonin - administration & dosage / Mice / Mice, Knockout / Microbiomes / Microbiota / Mucin / multidisciplinary / Pancreatitis-Associated Proteins - immunology / Pancreatitis-Associated Proteins - metabolism / Peptides / Receptors, Melatonin - metabolism / Science / Science (multidisciplinary) / Signal Transduction - drug effects / Signal Transduction - immunology / TLR4 protein / Toll-Like Receptor 4 - genetics / Toll-Like Receptor 4 - metabolism / Toll-like receptors / Wound healing