ABSTRACT
Studies of inflammatory bowel disease (IBD) have been inconclusive in relating microbiota with distribution of inflammation. We report microbiota, host transcriptomics, epigenomics and genetics from matched inflamed and non-inflamed colonic mucosa [50 Crohn's disease (CD); 80 ulcerative colitis (UC); 31 controls]. Changes in community-wide and within-patient microbiota are linked with inflammation, but we find no evidence for a distinct microbial diagnostic signature, probably due to heterogeneous host-microbe interactions, and show only marginal microbiota associations with habitual diet. Epithelial DNA methylation improves disease classification and is associated with both inflammation and microbiota composition. Microbiota sub-groups are driven by dominant Enterbacteriaceae and Bacteroides species, representative strains of which are pro-inflammatory in vitro, are also associated with immune-related epigenetic markers. In conclusion, inflamed and non-inflamed colonic segments in both CD and UC differ in microbiota composition and epigenetic profiles.
Subject(s)
Colitis, Ulcerative/immunology , Crohn Disease/immunology , Epigenesis, Genetic/immunology , Gastrointestinal Microbiome/immunology , Host Microbial Interactions/immunology , Adult , Aged , Bacteroides/genetics , Bacteroides/immunology , Bacteroides/isolation & purification , Biopsy , Caco-2 Cells , Case-Control Studies , Cohort Studies , Colitis, Ulcerative/genetics , Colitis, Ulcerative/microbiology , Colitis, Ulcerative/pathology , Colon/diagnostic imaging , Colon/immunology , Colon/microbiology , Colon/pathology , Colonoscopy , Crohn Disease/genetics , Crohn Disease/microbiology , Crohn Disease/pathology , DNA, Bacterial/isolation & purification , Enterobacteriaceae/genetics , Enterobacteriaceae/immunology , Enterobacteriaceae/isolation & purification , Epigenomics , Female , Gastrointestinal Microbiome/genetics , Host Microbial Interactions/genetics , Humans , Intestinal Mucosa/diagnostic imaging , Intestinal Mucosa/immunology , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Male , Middle Aged , RNA, Ribosomal, 16S/genetics , RNA-Seq , Young AdultABSTRACT
Campylobacter fetus is a species of gram-negative bacteria whose primary reservoir is the gastrointestinal tracts of cattle and sheep. Human infections are rare, though often invasive and sometimes fatal. In this paper, we studied an outbreak of six patients with a C. fetus infection and outlined their disease histories. In each case we were able to identify factors that led to a reduced resistance, including pre-existing illnesses and old age. Because of the unusually high number of patients that presented in a time period of only five months, the Community Health Services were commissioned to identify the source of infection. Using whole genome sequencing, we showed that 5 out of 6 patients belonged to the same cluster. This One Health approach resulted in the conclusion that the infection originated from unpasteurized sheep's milk processed into unripened cheese. Finally, various measures were put into place to prevent any further outbreaks.
