A discovery from a Korean veterinary lab reveals why some dogs struggle with ongoing health issues despite treatment for Cushing's disease, pointing to an unexpected culprit deep within the digestive system.
When Bella, a once-energetic 9-year-old Dachshund, began drinking excessive water, losing hair, and developing a pot-bellied appearance, her diagnosis of Cushing's disease came as a relief to her owners—finally, they had an answer. Yet, even after treatment with trilostane, the standard medication for Cushing's, Bella continued to experience ongoing health issues that puzzled her veterinarians.
Recent research has uncovered a missing piece in this puzzle: the gut microbiome. This article explores how Cushing's disease dramatically alters the gut ecosystem in dogs, changes that persist even after treatment and may explain those lingering health problems.
The gut microbiome comprises trillions of microorganisms, primarily bacteria, that live in the gastrointestinal tract. In healthy dogs, the gut is dominated by five main bacterial phyla: Firmicutes, Bacteroidetes, Fusobacteria, Proteobacteria, and Actinobacteria 8 .
These microbial communities form a complex ecosystem that does far more than aid digestion—they produce vital nutrients, regulate immune function, and even communicate with the brain through the gut-brain axis 4 6 .
When this delicate ecosystem falls out of balance, a state known as dysbiosis occurs. Dysbiosis represents more than just a change in bacterial populations—it involves functional disruptions in the metabolic activities that support canine health 4 . Research has revealed connections between gut dysbiosis and various health issues in dogs, from digestive problems to behavioral changes and metabolic disorders 2 6 8 .
The relationship between the gut and endocrine system is particularly fascinating. The hypothalamic-pituitary-adrenal (HPA) axis, which regulates stress response and cortisol production, engages in constant communication with gut bacteria 1 . This bidirectional relationship means that cortisol levels can reshape the gut microbiome, while certain gut bacteria can actually degrade and regulate cortisol levels 1 9 . When this delicate communication system goes awry, significant health consequences can follow.
A team of researchers at Konkuk University in Seoul, South Korea, conducted a pioneering study to investigate how hyperadrenocorticism specifically affects the canine gut microbiome 1 3 . Their work, published in October 2024, represents one of the first dedicated explorations of this relationship in dogs.
The researchers hypothesized that the chronically elevated cortisol levels characteristic of Cushing's disease would disrupt the gut microbiome, and that this disruption might persist even after trilostane treatment, potentially contributing to ongoing metabolic issues 1 .
The study included 24 dogs—15 diagnosed with hyperadrenocorticism and 9 healthy controls. The diagnosis of HAC followed established veterinary guidelines, requiring typical clinical signs combined with specific laboratory findings and confirmation through low-dose dexamethasone suppression testing or ACTH stimulation testing.
Fecal samples were collected from all participants, with special attention to standardized collection procedures. Dogs with significant gastrointestinal issues were excluded to isolate the influence of Cushing's disease specifically.
Five of the dogs with HAC received trilostane treatment (starting at 1 mg/kg every 12 hours), with follow-up fecal samples collected at a median of 41 days post-treatment.
Using advanced DNA sequencing techniques targeting the V3-V4 region of the bacterial 16S rRNA gene, the researchers could identify which bacteria were present and in what proportions. They employed multiple statistical approaches to compare microbiome diversity and composition between groups.
| Tool | Purpose |
|---|---|
| 16S rRNA Sequencing | Identify bacterial types and abundances |
| ACTH Stimulation Test | Assess adrenal function and cortisol |
| Shannon Diversity Index | Measure microbiome diversity |
| Beta Diversity Analysis | Compare community composition |
Dogs with HAC
Healthy Controls
Treated with Trilostane
Source: Kang et al. 2024 1
The findings from the Konkuk University study revealed striking differences between the gut ecosystems of healthy dogs and those with Cushing's disease 1 3 .
Dogs with HAC showed significantly less diverse gut microbiomes compared to healthy dogs, particularly in rare bacterial taxa.
Beta diversity analysis revealed a clear separation between the microbiomes of healthy dogs and those with HAC.
The research identified very particular alterations at both the phylum and genus levels.
| Taxonomic Level | Increased in HAC | Decreased in HAC |
|---|---|---|
| Phylum | Proteobacteria (Pseudomonadota), Actinobacteria | Firmicutes (Bacillota) |
| Genus | Bacteroides, Enterococcus, Corynebacterium, Escherichia, Proteus | Ruminococcus, Blautia |
Perhaps the most surprising finding was that these microbiome disruptions persisted in dogs treated with trilostane, even when their cortisol levels had improved 1 3 . This suggests that cortisol-induced damage to the gut ecosystem may not automatically repair itself when cortisol is controlled, potentially creating a self-perpetuating cycle of dysbiosis and metabolic dysfunction.
The persistence of gut dysbiosis even after trilostane treatment represents a crucial finding with significant clinical implications 1 3 . It suggests that current treatments for Cushing's disease may be incomplete, potentially explaining why some dogs continue to experience metabolic issues despite apparently successful cortisol management.
Specific bacterial strains could be introduced to counter the imbalances observed in HAC—perhaps boosting diminished Firmicutes populations or introducing cortisol-degrading bacteria.
This procedure, which involves transferring processed fecal material from a healthy donor to a recipient, aims to restore a balanced microbiome more comprehensively than individual probiotic strains.
Specialized fibers and compounds that nourish beneficial bacteria could help encourage the regrowth of diminished bacterial populations.
These microbiome-focused interventions could potentially be used alongside traditional trilostane treatment, creating a more comprehensive approach to managing Cushing's disease in dogs 1 .
For dog owners whose companions are affected by Cushing's disease, this research offers hope for more comprehensive treatment strategies in the future. It also highlights the incredible complexity of canine physiology and the importance of the often-overlooked microbial world within our pets.
The discovery that Cushing's disease dramatically alters the gut microbiome—and that these changes persist after treatment—represents a significant shift in our understanding of this common endocrine disorder. It suggests that effective management of Cushing's may eventually involve both controlling cortisol levels and actively restoring gut health.
As research in this field advances, the goal remains clear: not just to extend the lives of our canine companions, but to ensure those additional years are comfortable, healthy, and happy.
For further information about this groundbreaking study, refer to the original research publication: "Altered Gut Microbiome Composition in Dogs with Hyperadrenocorticism: Key Bacterial Genera Analysis" in Animals (2024) 1 .