Integrative analysis of single-cell RNA-seq and gut microbiome metabarcoding data elucidates macrophage dysfunction in mice with DSS-induced ulcerative colitis

• Published in: Communications biology 2024-06, Vol.7 (1), p.731-14, Article 731
• Main Authors: Hong, Dawon, Kim, Hyo Keun, Yang, Wonhee, Yoon, Chanjin, Kim, Minsoo, Yang, Chul-Su, Yoon, Seokhyun
• Format: Article
• Language: English
• Subjects: 38/91; 631/250/256/2515; 631/326/2565/2134; 64; 64/60; 692/699/1503/2745; Animals; Biomedical and Life Sciences; Cell differentiation; Cell interactions; Chronic illnesses; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - microbiology; CYBB protein; Dextran; Dextran Sulfate; Disease Models, Animal; DNA Barcoding, Taxonomic; Dysbacteriosis; Gastrointestinal Microbiome; Inflammatory bowel disease; Inflammatory bowel diseases; Intestinal microflora; Life Sciences; Lymphocytes T; Macrophages; Macrophages - microbiology; Male; Mice; Mice, Inbred C57BL; Microbiomes; Phenotypes; RNA, Ribosomal, 16S - genetics; RNA-Seq; rRNA; Single-Cell Gene Expression Analysis; Sodium sulfate; Taxonomy; Ulcerative colitis
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-06409-w

Ulcerative colitis (UC) is a significant inflammatory bowel disease caused by an abnormal immune response to gut microbes. However, there are still gaps in our understanding of how immune and metabolic changes specifically contribute to this disease. Our research aims to address this gap by examining mouse colons after inducing ulcerative colitis-like symptoms. Employing single-cell RNA-seq and 16 s rRNA amplicon sequencing to analyze distinct cell clusters and microbiomes in the mouse colon at different time points after induction with dextran sodium sulfate. We observe a significant reduction in epithelial populations during acute colitis, indicating tissue damage, with a partial recovery observed in chronic inflammation. Analyses of cell-cell interactions demonstrate shifts in networking patterns among different cell types during disease progression. Notably, macrophage phenotypes exhibit diversity, with a pronounced polarization towards the pro-inflammatory M1 phenotype in chronic conditions, suggesting the role of macrophage heterogeneity in disease severity. Increased expression of Nampt and NOX2 complex subunits in chronic UC macrophages contributes to the inflammatory processes. The chronic UC microbiome exhibits reduced taxonomic diversity compared to healthy conditions and acute UC. The study also highlights the role of T cell differentiation in the context of dysbiosis and its implications in colitis progression, emphasizing the need for targeted interventions to modulate the inflammatory response and immune balance in colitis. Chronic ulcerative colitis in mice is characterized by pro-inflammatory M1 macrophage phenotype and higher Nampt and NOX2 transcription, as well as a reduced taxonomic diversity in the mice gut microbiome.