Obesogenic diet-induced gut barrier dysfunction and pathobiont expansion aggravate experimental colitis

• Published in: PloS one Vol. 12; no. 11; p. e0187515
• Main Authors: Lee, June-Chul, Lee, Hae-Youn, Kim, Tae Kang, Kim, Min-Soo, Park, Young Mi, Kim, Jinyoung, Park, Kihyoun, Kweon, Mi-Na, Kim, Seok-Hyung, Bae, Jin-Woo, Hur, Kyu Yeon, Lee, Myung-Shik
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.11.2017; Public Library of Science (PLoS)
• Subjects: Animals; Antibiotics; Antimicrobial peptides; Bacteria; Biology and Life Sciences; Cell number; Colitis; Colitis - pathology; Diet; Diet, High-Fat - adverse effects; Dysbacteriosis; Enterobacteriaceae; Expansion; Fecal microflora; Gene expression; Goblet cells; Health aspects; Health sciences; High fat diet; Inflammatory bowel disease; Inflammatory bowel diseases; Influence; Internal medicine; Intestinal Mucosa - microbiology; Intestinal Mucosa - physiopathology; Intestine; Intestines; Laboratory animals; Medical research; Medicine; Medicine and Health Sciences; Metabolic disorders; Metabolic syndrome; Mice; Mice, Inbred C57BL; Microbiota - genetics; Mucin; Obesity; Paneth cells; Peptides; Permeability; Physiological aspects; Risk factors; RNA, Ribosomal, 16S - genetics; Rodents; Secretion; Small intestine; T cell receptors; Transplantation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0187515

Consumption of a typical Western diet is a risk factor for several disorders. Metabolic syndrome is the most common disease associated with intake of excess fat. However, the incidence of inflammatory bowel disease is also greater in subjects consuming a Western diet, although the mechanism of this phenomenon is not clearly understood. We examined the morphological and functional changes of the intestine, the first site contacting dietary fat, in mice fed a high-fat diet (HFD) inducing obesity. Paneth cell area and production of antimicrobial peptides by Paneth cells were decreased in HFD-fed mice. Goblet cell number and secretion of mucin by goblet cells were also decreased, while intestinal permeability was increased in HFD-fed mice. HFD-fed mice were more susceptible to experimental colitis, and exhibited severe colonic inflammation, accompanied by the expansion of selected pathobionts such as Atopobium sp. and Proteobacteria. Fecal microbiota transplantation transferred the susceptibility to DSS-colitis, and antibiotic treatment abrogated colitis progression. These data suggest that an experimental HFD-induced Paneth cell dysfunction and subsequent intestinal dysbiosis characterized by pathobiont expansion can be predisposing factors to the development of inflammatory bowel disease.