The canine gut microbiome is associated with higher risk of gastric dilatation-volvulus and high risk genetic variants of the immune system

• Published in: PloS one Vol. 13; no. 6; p. e0197686
• Main Authors: Hullar, Meredith A J, Lampe, Johanna W, Torok-Storb, Beverly J, Harkey, Michael A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.06.2018; Public Library of Science (PLoS)
• Subjects: Abundance; Adaptive immunity; Alleles; Animals; Antigens; Bacteria; Bacteroidetes; Biology and Life Sciences; Breeding; Cancer; Celiac disease; Diet; Dietary intake; Digestive system; Dog Diseases - genetics; Dog Diseases - immunology; Dog Diseases - microbiology; Dogs; Drb1 protein; Fecal microflora; Female; Fermentation; Gastric Dilatation - genetics; Gastric Dilatation - immunology; Gastric Dilatation - microbiology; Gastrointestinal Microbiome - genetics; Gastrointestinal Microbiome - immunology; Gene sequencing; Genes; Genetic aspects; Genetic diversity; Genetic variance; Genetic Variation; Health aspects; Health care; Health risk assessment; Health sciences; Hypotheses; Immune system; Immune System - immunology; Immune System - microbiology; Immunity; Inflammation; Inflammatory bowel disease; Influence; Intestinal microflora; Male; Medical research; Medicine and Health Sciences; Microbiomes; Microbiota; Microbiota (Symbiotic organisms); Mutation; Proteins; Proteobacteria; Public health; Regression analysis; Regression models; Rheumatoid arthritis; Risk; Risk Factors; RNA, Ribosomal, 16S - genetics; rRNA 16S; Stomach diseases; Stomach Volvulus - genetics; Stomach Volvulus - immunology; Stomach Volvulus - microbiology; TLR5 protein; Toll-like receptors; Womens health; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0197686

Large and giant dog breeds have a high risk for gastric dilatation-volvulus (GDV) which is an acute, life-threatening condition. Previous work by our group identified a strong risk of GDV linked to specific alleles in innate and adaptive immune genes. We hypothesize that variation in the genes of the immune system act through modulation of the gut microbiome, or through autoimmune mechanisms, or both, to predispose dogs to this condition. Here, we investigate whether differences in the canine fecal microbiome are associated with GDV and are linked to previously identified risk alleles. Fecal samples from healthy Great Danes (n = 38), and dogs with at least one occurrence of GDV (n = 37) were collected and analyzed by paired-end sequencing of the 16S rRNA gene. Dietary intake and temperament were estimated from a study-specific dietary and temperament questionnaire. Dogs with GDV had significantly more diverse fecal microbiomes than healthy control dogs. Alpha diversity was significantly increased in dogs with GDV, as well as dogs with at least one risk allele for DRB1 and TRL5. We found no significant association of dietary intake and GDV. Dogs with GDV showed a significant expansion of the rare lineage Actinobacteria (p = 0.004), as well as a significantly greater abundance of Firmicutes (p = 0.004) and a significantly lower abundance of Bacteroidetes (p<0.004). There was a significant difference in the abundance of 10 genera but after correction for multiple comparisons, none were significant. Bacterial phyla were significantly different between controls and dogs with GDV and at least one risk allele for DRB1 and TRL5. Actinobacteria were significantly higher in dogs with GDV and with one risk allele for DRB1 and TLR5 but not DLA88 genes. Furthermore, Collinsella was significantly increased in dogs with at least one risk allele for DRB1 and TLR5. Logistic regression showed that a model which included Actinobacteria, at least one risk allele,and temperament, explained 29% of the variation in risk of GDV in Great Danes. The microbiome in GDV was altered by an expansion of a minor lineage and was associated with specific alleles of both innate and adaptive immunity genes. These associations are consistent with our hypothesis that immune genes may play a role in predisposition to GDV by altering the gut microbiome. Further research will be required to directly test the causal relationships of immune genes, the gut microbiome and GDV.