Novel Diagnostic Test for Canine and Feline Microbiota Dysbiosis

Common knowledge for years has been that good and bad bacteria – also known as microbiota – live in the gastrointestinal systems (microbiome) of mammals. Yet, the majority of commercially available diagnostic tests still only test for the bad, harmful bacteria – until now.

The Canine and Feline Microbiota Dysbiosis Index (DI) – available at Texas A&M University (TAMU) – analyzes the abundances of seven different good and bad bacteria in feces, and then calculates a single number that indicates the level of gut dysbiosis. This imbalance – dysbiosis – of these key bacteria is often associated with broad spectrum antibiotic use or chronic enteropathies.

The operative word here is “associated” because this test does not diagnose enteropathies. Enteropathies are currently diagnosed with a variety of tests involving bloodwork, enteroscopy, endoscopy, or by trial and error approaches.

In dogs alone, there are several documented types of enteropathies such as histiocytic ulcerative colitis, protein-losing enteropathy, immunosuppressant-responsive enteropathy, antibiotic-responsive enteropathy, steroid-responsive enteropathy, food-responsive enteropathy, lymphocytic-plasmacytic gastroenteritis, and eosinophilic gastroenteritis.

While all enteropathies are inflammations somewhere within the intestinal tract, the root causes of each enteropathy are often enigmatic, complex, multifactorial, and different from another. So, accepted treatment options are limited and, again, somewhat varied based on the type of enteropathy.

Enteropathies – and treatments for the enteropathy or another disease – influence and impact the good and bad bacteria in the gut and their associated bodily mechanisms. So, the noninvasive DI can be run to pinpoint how the microbiota are doing at any single point in time. Additionally, the test can be used longitudinally to gauge the bacterial response to disease progression, response to therapeutics, or provide clues to manage disease. Not only does this help the individual dogs and cats, but also provides a resource database that can help guide disease management to slow its progression in the future.

Dysbiosis Index Studies

Thus far, the studies using the DI have provided important findings such as the length of dysbiosis caused by antibiotic use. We have always known that broad spectrum antibiotics target not only bad bacteria, but also good bacteria. Thus, their use can cause a dysbiosis in the gut. The question is for how long does this imbalance persist? TAMU’s research has documented at least four weeks after the discontinuation of 14-day metronidazole in dogs.

In a longitudinal study involving dogs diagnosed with steroid-responsive enteropathy, findings based on the DI suggest that corticosteroids can help manage the disease, but that dysbiosis can persist in dogs. While we are disappointed by this finding, we acknowledge that a suitable alternative treatment has not been found or developed yet.

The DI also has helped the researchers discover that probiotics can accelerate the normalization of the microbiome and suppress the presence of invasive Clostridium perfringens in dogs diagnosed with acute hemorrhagic diarrhea syndrome.

Peptacetobacter hiranonis

Formally known as Clostridium hiranonis, Peptacetobacter hiranonis (P hiranonis) is an important bacterium for dogs, as it converts primary bile acids into secondary bile acids. Those secondary bile acids have anti-inflammatory and anti-pathogenic powers by suppressing bad bacteria such as Clostridium difficile, Clostridium perfringens, and Escherichia coli. So, a suboptimum amount of P hiranonis along with a high DI are associated with antibiotic use, enteropathies, and exocrine pancreatic insufficiency.

A recent study indicated that P hiranonis had the same critical function for cats. 15 out of 16 cats with chronic enteropathies had a fecal abundance of P hiranonis below the reference interval, which might be the cause of higher levels of primary bile acids found in their feces.

Fecal Microbiota Transfer Therapy

Today, much focus has been placed on the role of fecal microbiota transfer (FMT) and whether it works.

For those who are unfamiliar with FMT, the process transfers feces from a healthy human or animal donor to the same species with a gastric condition. The Food and Drug Administration recently approved Vowst, a capsule, for use in humans. Parallel FMT use in companion animals is available from groups such as Dr. Margo Roman, Animal Biome, and TAMU.

TAMU along with researchers at Helsinki University published a study in early 2023 that demonstrated 31 out of 41 dogs that received FMT had less diarrhea and became more active.

Using the DI, 16 dogs with gastrointestinal issues had samples taken before and after treatment. Dogs with a higher number on the DI – which indicated greater dysbiosis – did not respond as well to FMT as dogs with lower original numbers on the DI scale. This bodily response was to be expected because the dogs with greater dysbiosis do have more clinical disease to overcome. They may need additional treatments, different fecal donors, or varying amounts of certain bacteria. That will need to be determined in the future.

As previously mentioned, P hiranonis plays a significant role in the fight against gastric dysbiosis in dogs. So, these researchers highly recommend that all donor dogs should be tested not only for parasites and bad bacteria, but also to ensure they have adequate amounts of P hiranonis. This DI test is perfectly suited to determine the appropriate amount of P hiranonis from healthy donor dogs. Please remember, however, that the healthy donor people and dogs may eat food ingredients that the ill recipients cannot tolerate; thus, donor and recipient people and dogs need to be matched for food tolerances, including glutens.

Food-Responsive Therapy

Before FMT is sought, the standard protocol is to try food changes. We respectfully disagree with TAMU on its suggested approach. TAMU suggests using either a hydrolyzed diet or a food elimination trial.

The hydrolyzation process chemically breaks down a protein like chicken to the point that it no longer causes an “allergic” reaction in a dog or cat that is in fact sensitive or intolerant to said protein. However, several peer-reviewed studies have demonstrated that hydrolyzed diets still elicit adverse events albeit in lesser amounts, may not work in an individual case, and may not have the intended effects. As renowned veterinary nutritionist Nicholas Cave stated, “Any reduction in antigenicity or clinical reactivity at which point a diet could be considered ‘hypoallergenic’ is arbitrary, however, unless it is absolute.”

A food elimination trial may be a better option. However, these typically requires up to 6 weeks of feeding a single ingredient and client compliance is costly and unreliable. Further, food intolerances may be delayed and clinical signs of dysbiosis could re-emerge.

Rachel Pilla and Jan Suchodolski of TAMU noted in a 2019 paper, “The difference in response to treatment between dogs with FRD (food-responsive diarrhea/enteropathy) and dogs with IBD (idiopathic inflammatory bowel diarrhea/enteropathy) can likely be attributed to the differences in the pathogenesis of the enteropathy. While dogs with IBD have an inflammatory process that seems to arise from a combination of genetic predisposition and environmental factors, dogs with FRD have an inflammatory process that is driven by the constant presence of an antigen of alimentary origin.”

We concur with that statement, but believe more should be done to rule out FRD.

For example, they categorize steroid-responsive enteropathy as IBD. From what we surmise, they mean that if symptoms persist while feeding a hydrolyzed diet, and re-emerge after food elimination trials or FMT, then steroids (corticosteroids) and/or immunosuppressants are the next course of action.

But, steroids have long-term side effects and correctly are becoming unpopular.

Another commonly overlooked issue is that a companion dog or cat could suffer from FRD and IBD. For instance, a dog could be taking steroids for IBD, but continue to have occasional bouts of diarrhea. The question is from what? Was he overfed? Did he get into something outside? Was it something in the food?

Food elimination recommendations for humans diagnosed with certain enteropathies have been around for years. For example, youngsters born with Celiac Disease should avoid all glutens, as should those with Hashimoto’s thyroiditis. Pets also can have gluten intolerance especially if they also have autoimmune thyroid disease. Companion dogs with protein-losing enteropathy, a genetic condition, are often placed on low fat diets.

We would prefer if parents of companion pets with enteropathies complete both the DI and NutriScan Food Sensitivity & Intolerance Test every 12-18 months. The DI will reveal the presence of dysbiosis at a particular moment and provide an idea of disease progression, regression or stagnation. NutriScan will indicate the foods that are the problem or are exacerbating IBD.

Additional References

Suchodolski, Jan S. “Analysis of the gut microbiome in dogs and cats.” Veterinary clinical pathology vol. 50 Suppl 1,Suppl 1 (2022): 6-17. doi:10.1111/vcp.13031, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9292158/.

Sung, Chi-Hsuan et al. “Dysbiosis index to evaluate the fecal microbiota in healthy cats and cats with chronic enteropathies.” Journal of feline medicine and surgery vol. 24,6 (2022): e1-e12. doi:10.1177/1098612X221077876, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9160961/.

Ziese, Anna-Lena, and Jan S Suchodolski. “Impact of Changes in Gastrointestinal Microbiota in Canine and Feline Digestive Diseases.” The Veterinary clinics of North America. Small animal practice vol. 51,1 (2021): 155-169. doi:10.1016/j.cvsm.2020.09.004, https://www.sciencedirect.com/science/article/pii/S0195561620301029.

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