Axl alleviates DSS-induced colitis by preventing dysbiosis of gut microbiota

• Published in: Scientific reports Vol. 13; no. 1; p. 5371
• Main Authors: Yee, Su-Min, Choi, Harim, Seon, Jeong-Eun, Ban, Yu-Jin, Kim, Min-Jae, Seo, Jae-Eun, Seo, Ja Hun, Kim, Sehyeon, Moon, Seo Hee, Yun, Chul-Ho, Lee, Hyang Burm, Kang, Hyung-Sik
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/249/2510/257; 631/250/256; 631/250/347; Animals; Antibiotics; Antimicrobial peptides; Axl protein; Colitis; Colon - microbiology; Dextran Sulfate - toxicity; Digestive system; Digestive tract; Disease Models, Animal; Dysbacteriosis; Dysbiosis - chemically induced; Gastrointestinal Microbiome; Homeostasis; Humanities and Social Sciences; Immune response; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - microbiology; Innate immunity; Intestinal microflora; Intestine; Mice; Mice, Inbred C57BL; Microbiota; Microenvironments; multidisciplinary; Pathogenesis; Peptides; Protein-tyrosine kinase receptors; Proteobacteria; Science; Science (multidisciplinary); Therapeutic targets
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-32527-2

Axl is a tyrosine kinase receptor, a negative regulator for innate immune responses and inflammatory bowel disease (IBD). The gut microbiota regulates intestinal immune homeostasis, but the role of Axl in the pathogenesis of IBD through the regulation of gut microbiota composition remains unresolved. In this study, mice with DSS-induced colitis showed increased Axl expression, which was almost entirely suppressed by depleting the gut microbiota with antibiotics. Axl −/− mice without DSS administration exhibited increased bacterial loads, especially the Proteobacteria abundant in patients with IBD, significantly consistent with DSS-induced colitis mice. Axl −/− mice also had an inflammatory intestinal microenvironment with reduced antimicrobial peptides and overexpression of inflammatory cytokines. The onset of DSS-induced colitis occurred faster with an abnormal expansion of Proteobacteria in Axl −/− mice than in WT mice. These findings suggest that a lack of Axl signaling exacerbates colitis by inducing aberrant compositions of the gut microbiota in conjunction with an inflammatory gut microenvironment. In conclusion, the data demonstrated that Axl signaling could ameliorate the pathogenesis of colitis by preventing dysbiosis of gut microbiota. Therefore, Axl may act as a potential novel biomarker for IBD and can be a potential candidate for the prophylactic or therapeutic target of diverse microbiota dysbiosis-related diseases.