Gut microbiota facilitate chronic spontaneous urticaria

• Published in: Nature communications Vol. 15; no. 1; pp. 112 - 17
• Main Authors: Zhu, Lei, Jian, Xingxing, Zhou, Bingjing, Liu, Runqiu, Muñoz, Melba, Sun, Wan, Xie, Lu, Chen, Xiang, Peng, Cong, Maurer, Marcus, Li, Jie
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.01.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 38; 42; 45; 49; 631/250/256; 631/250/347; 631/326/2565/2134; 692/700; 96; Animal models; Animals; Blood; Blood levels; Chronic Urticaria; Dermatitis; Digestive system; Dysbacteriosis; Dysbiosis - microbiology; Fatty acids; Fatty Acids, Volatile - metabolism; Gastrointestinal Microbiome; Gastrointestinal tract; Gut microbiota; Humanities and Social Sciences; Humans; Inflammation; Inflammatory response; Intestinal microflora; Intestine; Klebsiella; Klebsiella pneumoniae; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Metabolites; Metabolomics; Metagenomics; Mice; Microbiomes; Microbiota; Microorganisms; multidisciplinary; Permeability; Roseburia; Science; Science (multidisciplinary); Skin diseases; Transplantation; Urticaria
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-44373-x

Chronic spontaneous urticaria (CSU) comes with gut dysbiosis, but its relevance remains elusive. Here we use metagenomics sequencing and short-chain fatty acids metabolomics and assess the effects of human CSU fecal microbial transplantation, Klebsiella pneumoniae , Roseburia hominis , and metabolites in vivo. CSU gut microbiota displays low diversity and short-chain fatty acids production, but high gut Klebsiella pneumoniae levels, negatively correlates with blood short-chain fatty acids levels and links to high disease activity. Blood lipopolysaccharide levels are elevated, link to rapid disease relapse, and high gut levels of conditional pathogenic bacteria. CSU microbiome transfer and Klebsiella pneumoniae transplantation facilitate IgE-mediated mast cell(MC)-driven skin inflammatory responses and increase intestinal permeability and blood lipopolysaccharide accumulation in recipient mice. Transplantation of Roseburia hominis and caproate administration protect recipient mice from MC-driven skin inflammation. Here, we show gut microbiome alterations, in CSU, may reduce short-chain fatty acids and increase lipopolysaccharide levels, respectively, and facilitate MC-driven skin inflammation. Chronic spontaneous urticarial is an inflammatory skin disease which has been linked to intestinal dysbiosis. Here the authors implicate intestinal dysbiosis with the inflammatory response in a murine model of urticaria.