We’re Fighting Bloat
The following is from Dr. Michael A. Harkey, chief investigator for the AKC/CHF research study entitled “The Genetics of Bloat in German Shepherd Dogs: The Roles of Immune System Genes and the Gut Microbes”. The American German Shepherd Dog Charitable Foundation is proud to sponsor this research study.
Update From Dr. Harkey: We are just moving out of the collection phase and into the analysis phase of the study. So we do not yet have big enough numbers for strong statistical significance. But we do see one interesting number emerging for the DRB1 gene. In Great Danes, the DRB1: 1201 allele was associated with GDV. In the German Shepherds, this allele is already emerging as a significant risk factor. 1201 occurs at a 13 fold higher frequency in GDV dogs than in controls, with a p value of 0.0013. Allele 1101 appears to have a protective effect, being twice as frequent in control dogs with a p value of 0.0089. We don’t have enough data yet to see significant associations with DLA88, and TLR5 shows no trend at all. Interestingly, the B allele of TLR5, which associated with risk for GDV in Great Danes, is completely missing from the German Shepherds. A new allele (“C”), which has never been reported, has been seen 22 times in our GSD study, evenly distributed between GDV and control groups.
The microbiome analysis is still at an early stage. We are just getting the last samples in this week, and much of the processing for bacterial DNA is done. But the high throughput sequencing and analysis are waiting for the last samples. They will all be sequenced together and the analysis should be fairly
The causes of bloat are poorly understood and may involve multiple triggers. Certainly, genetics plays a role. In addition, the scientific literature implicates a variety of factors, including age, gender, diet, exercise, position of the food bowl, stress, and even weather conditions. Except for stress, much of the data is equivocal My working theory is that specific genetic factors shift the gut bacterial population (microbiome) to an unhealthy state (dysbiosis), which predisposes the dog to bloat. Then some non-genetic trigger, such as stress, or an unusual meal can set off an episode of bloat in a genetically predisposed susceptible.
The logic for this theory is complicated, but this is it in a nutshell. Certain genes of the immune system (DLA genes in dogs) are responsible for detecting foreign invaders (like bacteria) and starting the process of destroying those invaders. These genes are highly variable, each having hundreds of variants (alleles) within the larger population of dogs. So each individual dog has a pretty unique array of these alleles, and a pretty unique ability to detect and destroy the thousands of potential invaders. These same genes influence the types of bacteria that are allowed to grow in the gut. So the microbiome of each dog can vary, due to its DLA genes. Our hypothesis is that certain “risk” alleles of the DLA genes cause dysbiosis of the gut microbiome, which in turn, predisposes the dog to bloat.
Our work in Great Danes supports this hypothesis. It showed that each of 3 immune genes has a single “risk” allele that predisposes carriers to bloat. A Great Dane carrier is three times more likely to bloat than a non-carrier. This study is now in press at the American Journal of Veterinary Research. A study of microbiome composition in this same group of dogs showed significant changes in the bacterial population, associated with bloat. These changes included a two-fold change in the ratio of the two most abundant bacterial phyla, Firmicutes and Bacteroidetes. These are major changes, but we do not yet know the biological significance of these changes, but they are clearly associated with the bloat group. The microbiome study is about to be submitted to PLOS ONE
Now, with the help of your support, we are asking if these same factors, DLA genes and gut microbiome, play a role in bloat in German Shepherds. We do not yet know if the data from Great Danes is breed-specific, or if it might apply to all dogs. If we find similar associations in German Shepherds the implication is that our hypothesis holds for dogs in general. If so, we may be able to establish a universal genetic test for predisposition to bloat. The microbiome data may lead to probiotic or dietary therapies to prevent bloat, even in predisposed dogs. So now that we have your financial support, we are excited to start to answer some of these questions.
For information or to donate
To the Health of the Breed