Dr. Donna Raditic Explains

Dr. Donna Raditic, DVM, DACVIM (Nutrition), CVA, owner and founder of Nutrition and Integrative Medicine Consultants, explains the microbiota-gut-brain axis (MGBA) role in canine behavioral and neurologic disorders.

MGBA Overview

The microbiota-gut-brain axis (MGBA) describes bidirectional pathways that enable gut microbiota to affect neurologic functions, cognition, and behavior while the brain modulates gut physiology, functions, and microbiota composition. Rodent and human studies have shown that the MGBA may contribute to development of anxiety, depression, autism spectrum disorders, bipolar disorder, schizophrenia, Parkinson disease, amyotrophic lateral sclerosis, chronic fatigue syndrome, and epilepsy. In veterinary medicine, studies have evaluated the role of the MGBA in dogs with behavioral disorders, idiopathic epilepsy, and canine cognitive dysfunction syndrome, otherwise known as MGBA diseases.

Key Findings

• Studies have evaluated the role of the MGBA in dogs with behavioral disorders, idiopathic epilepsy, and canine cognitive dysfunction syndrome.
• Studies suggest that dysbiosis interferes with normal MGBA functions and can result in dysregulated immune signaling, increased neuroinflammation, oxidative stress, and disruptions in blood-brain barrier integrity.
• The bidirectional nature of the MGBA implies not only that the brain can influence gut health but also that gut-targeted interventions may be therapeutic for dogs with behavioral disorders, idiopathic epilepsy, and canine cognitive dysfunction syndrome.
• Outcomes for MGBA diseases are optimal when gut microbiota and mental health are treated concurrently.
• Because comorbidities are common among patients with MGBA diseases, management is challenging and prognosis is often poor.

Veterinary Applications

The concept of the microbiota-gut-brain axis stems from growing evidence highlighting the intricate communication between the microbiota, gut, and brain. The axis is bidirectional and integrates neural, endocrine, immune, and metabolic pathways. Gut microbes influence neurologic functions, cognition, and behavior, and the brain and nervous system modulate gut physiology, functions, and microbiota composition.1,2 Microbiota can interact with the brain via multiple routes, including gut hormone signaling, the vagus nerve, the immune system, and microbial metabolites (e.g., short-chain fatty acids, neurotransmitters, precursors).1-3

In human medicine, studies have shown that gut microbiota affect cognition, mood, and overall psychological wellbeing in healthy persons as well as those with neuropsychologic and neurologic disorders.1-3 Changes in gut microbiota population can lead to neurotransmitter imbalances, oxidative stress, and neuroinflammation.1-3 Gut dysbiosis has been associated with anxiety, depression, autism spectrum disorders, bipolar disorder, schizophrenia, eating disorders, Parkinson disease, amyotrophic lateral sclerosis, migraines, multiple sclerosis, post-traumatic stress disorder, chronic fatigue syndrome, and epilepsy.3-6 However, the exact mechanisms are not well explored, and observed microbial changes across studies are inconsistent.

Approaches to the mental health and neurologic disorders of veterinary patients can be expanded by the valuable insights gained from the growing number of studies regarding human mental health, neurologic disorders, and the role of the MGBA. Understanding this area of research is critical, as the bidirectional nature of the MGBA implies that not only can the brain influence gut health but gut-targeted interventions may provide mental health and neuroprotective benefits.1-6

Therapeutics that improve gut health and reestablish normal MGBA communications could be applied to veterinary patients. To date, veterinary studies of the role of the MGBA include canine behavioral disorders and neurologic diseases such as canine cognitive dysfunction syndrome (CCDS) and idiopathic epilepsy (IE).7

Dysbiosis and the MGBA

In healthy individuals, the microbial ecosystem is balanced. A disturbed balance can lead to a state of dysbiosis, which may be characterized by reduced bacterial diversity, depletion of beneficial bacteria, and/or proliferation of potential pathogens resulting in changes in metabolic functions.8 In human microbiota research, there are concerns about the different methods attempted to identify or define dysbiosis, such that some authors state there is no common definition of dysbiosis.9 This author acknowledges that those same concerns exist in veterinary medicine, making it difficult to compare MGBA studies. In addition, there is currently no distinct identifiable dysbiosis pattern in dogs with MGBA-associated diseases.

What is known from human and rodent studies is that health, including mental health, depends on a stable MGBA maintaining a homeostatic balance of gastrointestinal bacteria. Microbial diversity and stability are often used as key indicators of gut health, whereas decreased diversity and instability are associated with chronic disease and metabolic dysfunction.5-7

Stressors, especially chronic stress, increase sympathetic nervous system and hypothalamic-pituitary-adrenal axis activity that dysregulates gut functions and affects microbial ecosystem balance. Dysbiosis can also result from infections, poor diet, inactivity, environmental factors, and antibiotic use. Dysbiosis interferes with the normal MGBA by leading to dysregulated immune signaling, increased neuroinflammation, oxidative stress, and disruptions in blood-brain barrier integrity.2,7 The human literature indicates increasing recognition that dysbiosis is associated with a range of neurologic disorders, including developmental and neurodegenerative diseases, neuroimmune conditions, and behavioral syndromes.2,4,5 Recognition of the role of the MGBA in human studies strongly suggests that brain and gut microbiota may both need to be targeted to fully and effectively reverse the core signs associated with neuropsychologic, neurologic, and neurodegenerative disorders.5-7

Veterinary studies investigating the role of the MGBA in dogs with different behavioral phenotypes and memory demonstrate some results similar to those seen in human studies.10-14 Kubinyi et al assessed cognition in 29 client-owned dogs by using a memory test and analyzing fecal samples to determine whether short-term memory and age are linked to gut microbiota composition.15 In older dogs, they found a lower proportion of Fusobacteria; in dogs with better memory performance, they found fewer Actinobacteria. These results may align with studies of human Alzheimer disease that report a high abundance of Actinobacteria. A few microbiota studies comparing dogs with IE versus healthy controls reported mixed results.16-19 More research is needed, but evidence that the MGBA plays a role in the mental and neurologic health of veterinary patients is increasing.

Comorbidities and Management

Understanding the role of the MGBA in dogs with behavioral and neurologic disorders is imperative, as MGBA-associated diseases have historically been difficult to treat and manage. Veterinary patients with behavioral disorders, CCDS, and/or IE are frequently euthanized due to poor quality of life (TABLE 1).

In addition, MGBA diseases are often associated with comorbidities, which complicate diagnosis and therapeutics (TABLE 2).32 The term “comorbidity” describes the co-occurrence of 2 distinct diseases in the same individual at a rate exceeding what would be expected by chance.

Veterinary patients with MGBA disease may be presented to the general practitioner with a primary complaint describing a behavioral disorder (e.g., anxiety, noise phobia). Dogs with MGBA disease can also exhibit recurring or chronic gastrointestinal issues. Studies suggest that 20% to 30% of companion animal visits to veterinarians are for vomiting or diarrhea or both.33 To determine if these patients have MGBA-associated diseases, the general practitioner will need to obtain a thorough history to evaluate both mental and gastrointestinal health. For the patient with behavioral concerns, questions about gastrointestinal health (e.g., appetite, stool quality) should be investigated. For the patient with common and/or uncommon gastrointestinal signs, the patient’s mental health should be assessed.34

In the author’s clinical experience, clients easily and frequently report changes in characteristics such as stools and appetite but often do not realize that their dog has underlying concurrent behavioral disorders.

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Dr. Raditic’s expertise is documented in articles written by Donna Raditic.

Updated December 2024