Flagellin-elicited adaptive immunity suppresses flagellated microbiota and vaccinates against chronic inflammatory diseases

• Published in: Nature communications Vol. 10; no. 1; pp. 5650 - 15
• Main Authors: Tran, Hao Q., Ley, Ruth E., Gewirtz, Andrew T., Chassaing, Benoit
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.12.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/31; 14/32; 38; 38/77; 49; 631/250/2152/2153/1291; 631/326/2565/2134; 64; 64/60; 692/163/2743/393; 692/4020/1503/257; Adaptive Immunity; Animals; Antibodies; Antibodies, Bacterial - immunology; Bacterial Vaccines - administration & dosage; Bacterial Vaccines - genetics; Bacterial Vaccines - immunology; Colitis; Colitis - genetics; Colitis - immunology; Colitis - microbiology; Colitis - prevention & control; Encroachment; Feces - microbiology; Flagellin; Flagellin - administration & dosage; Flagellin - genetics; Flagellin - immunology; Gastrointestinal Microbiome; Humanities and Social Sciences; Humans; Immunoglobulin A - immunology; Inflammatory diseases; Interleukin-10 - genetics; Interleukin-10 - immunology; Intestinal microflora; Intestinal Mucosa - immunology; Intestinal Mucosa - microbiology; Lymphocytes; Male; Metabolic disorders; Metabolic syndrome; Mice, Inbred C57BL; Microbiota; Mucosa; multidisciplinary; Obesity - genetics; Obesity - immunology; Obesity - microbiology; Salmonella typhimurium - genetics; Salmonella typhimurium - immunology; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-13538-y

Alterations in gut microbiota composition are associated with metabolic syndrome and chronic inflammatory diseases such as inflammatory bowel disease. One feature of inflammation-associated gut microbiotas is enrichment of motile bacteria, which can facilitate microbiota encroachment into the mucosa and activate pro-inflammatory gene expression. Here, we set out to investigate whether elicitation of mucosal anti-flagellin antibodies by direct administration of purified flagellin might serve as a general vaccine against subsequent development of chronic gut inflammation. We show, in mice, that repeated injection of flagellin elicits increases in fecal anti-flagellin IgA and alterations in microbiota composition, reduces fecal flagellin concentration, prevents microbiota encroachment, protects against IL-10 deficiency-induced colitis, and ameliorates diet-induced obesity. Flagellin’s impact on the microbiota is B-lymphocyte dependent and, in humans, obese subjects exhibit increased levels of fecal flagellin and reduced levels of fecal flagellin-specific IgA, relative to normal weight subjects. Thus, administration of flagellin, and perhaps other pathobiont antigens, may confer some protection against chronic inflammatory diseases. Gut microbiota alterations, including enrichment of flagellated bacteria, are associated with metabolic syndrome and chronic inflammatory diseases. Here, Tran et al. show, in mice, that elicitation of mucosal anti-flagellin antibodies protects against experimental colitis and ameliorates diet-induced obesity.