Gut-derived Enterococcus faecium from ulcerative colitis patients promotes colitis in a genetically susceptible mouse host

• Published in: Genome Biology Vol. 20; no. 1; p. 252
• Main Authors: Seishima, Jun, Iida, Noriho, Kitamura, Kazuya, Yutani, Masahiro, Wang, Ziyu, Seki, Akihiro, Yamashita, Taro, Sakai, Yoshio, Honda, Masao, Yamashita, Tatsuya, Kagaya, Takashi, Shirota, Yukihiro, Fujinaga, Yukako, Mizukoshi, Eishiro, Kaneko, Shuichi
• Format: Journal Article
• Language: English
• Published: England BioMed Central 25-11-2019; BMC
• Subjects: Animals; Case-Control Studies; Colitis - etiology; Colitis - pathology; Colitis, Ulcerative - drug therapy; Colitis, Ulcerative - microbiology; Colon; Colon - pathology; Crohn Disease - microbiology; Crohn’s disease; Disease; Disease Models, Animal; DNA sequencing; Drug Therapy, Combination; Dysbacteriosis; E coli; Enterococcus faecalis - genetics; Enterococcus faecalis - pathogenicity; Fecal Microbiota Transplantation; Feces; Feces - microbiology; Female; Gastrointestinal Microbiome; Gene expression; Genomes; Genotypes; Humans; Inflammation; Inflammatory bowel disease; Inflammatory bowel diseases; Interleukin 1; Interleukin 10; Interleukin-10 - genetics; Intestinal microflora; Male; Metagenome; Mice; Mice, Inbred C57BL; Microbiota; Pathogenesis; Pathology; Patients; Probiotics; Strains (organisms); Taxonomy; Transplantation; Ulcerative colitis; Inflammatory bowel disease; Microbiota; Metagenome; Crohn’s disease
• ISSN: 1474-760X; 1474-7596; 1474-760X
• DOI: 10.1186/s13059-019-1879-9

Recent metagenomic analyses have revealed dysbiosis of the gut microbiota of ulcerative colitis (UC) patients. However, the impacts of this dysbiosis are not fully understood, particularly at the strain level.
We perform whole-genome shotgun sequencing of fecal DNA extracts from 13 healthy donors and 16 UC and 8 Crohn's disease (CD) patients. The microbiota of UC and CD patients is taxonomically and functionally divergent from that of healthy donors, with E. faecium being the most differentially abundant species between the two microbial communities. Transplantation of feces from UC or CD patients into Il10
mice promotes pathological inflammation and cytokine expression in the mouse colon, although distinct cytokine expression profiles are observed between UC and CD. Unlike isolates derived from healthy donors, E. faecium isolates from the feces of UC patients, along with E. faecium strain ATCC 19434, promotes colitis and colonic cytokine expression. Inflammatory E. faecium strains, including ATCC 19434 and a UC-derived strain, cluster separately from commercially available probiotic strains based on whole-genome shotgun sequencing analysis. The presence of E. faecium in fecal samples is associated with large disease extent and the need for multiple medications in UC patients.
E. faecium strains derived from UC patients display an inflammatory genotype that causes colitis.