The Gut-brain Axis

The microbiota use several different channels to communicate with the brain and central nervous system (CNS), including:

• The enteric nervous system (ENS): Sometimes called the ‘second brain,’ hundreds of millions of neurons that extend along the length of the digestive tract comprise the ENS. This system communicates subtle changes within the gastrointestinal tract to the brain via the vagus nerve. Primary pathways through the vagus nerve mediate communications between the gut microbes and the CNS.
• The sympathetic nervous system: The release of adrenaline and noradrenaline from the brain and adrenal glands leads to the behavioral responses of fight, flight, or freeze, and can also alter gut motility.
• The hypothalamic-pituitary-adrenal axis: This system mediates the secretion of cortisol, which influences the immediate stress response. Research has shown that gut microbiota may affect the development of these neural systems that govern the endocrine response to stress.
• Immune signaling: Another way that the gut microbiota seem to alter messages to the brain. Evidence shows that the gut microbiota can affect immune cells located in the gut mucosa that modify the activity of sensory neurons of the ENS. These immune cells release cytokines that are important in host responses to inflammation and infection.
• Gut bacterial metabolites: Through the fermentation and metabolism of indigestible fibers (e.g. prebiotics), the gut microbiota produce short chain fatty acids (SCFAs) including acetate, butyrate, lactate and propionate. SCFAs have been singled out as particularly important metabolites with possible influences on brain function. Additionally, the gastrointestinal tract and its bacteria contribute to the body’s production of hormones and neurotransmitters, including dopamine and serotonin.

Research has shown many links between dysbiosis (an imbalanced microbiome) and conditions such as Alzheimer’s disease, epilepsy, and anxiety in human patients¹ as well as cognitive impairment, stress- and fear-related behaviors, and epilepsy in dogs.^2-5  An association between chronic enteropathy and compromised emotional health in dogs has been described.⁶

Pet stress behavior is a major concern for pet owners, and chronic stress can negatively impact animal welfare and the pet-owner bond. Highly stressed pets may be prone to chronic behavioral and health issues and may have a shorter life span.⁷ Stress-related and anxious-like behaviors can be difficult to manage, can place a burden on the human-pet bond, and may lead to relinquishment.^8,9   Approximately 70% of dogs demonstrate stress-related behaviors.³

Pet owners may not recognize all signs of fear and stress, or may only reach out once the problem has escalated to the point of crisis.¹⁰

The role of the veterinary general practitioner in identifying and treating their patients’ behavior problems is a crucial one.¹¹

In a blinded, placebo-controlled, crossover study, Purina scientists discovered that dogs supplemented with BL999 demonstrated significant improvements in four day-to-day stress-related behaviors (barking, jumping, spinning, pacing) compared to when they received a placebo.¹⁵ A majority of the dogs studied also showed lower heart rates and salivary cortisol levels.¹⁵ 

Supplementation with BL999 reduced stress-related behaviors in dogs encountering events that they might encounter in their everyday life (e.g., meeting strangers, hearing loud noises) and could serve as a useful tool in a comprehensive behavioral management plan.

An external placebo-controlled, blinded study showed that compared to a placebo, cats supplemented with BL999 were significantly more likely to interact with evaluators and significantly less likely to pace when housed individually.¹⁶ Supplemented cats were also significantly less likely to have abnormal cortisol levels during periods of minor stress.¹⁶

• The gut microbiota are essential to the constant bidirectional communication between the gut and brain via the nervous system, immune system, neuroendocrine pathways and metabolites.
• Accruing evidence suggests that gut microbiota help shape normal neural development, brain biochemistry and behavior.
• Nutritional interventions that can influence the gut microbiota composition have the potential to alter behavior and mood.
• Stress and fear play a role in many behavioral disorders of dogs and can negatively affect the physical and mental health of the pet as well as the bond between owners and their pets. 
• Purina's scientists have shown that a strain of B. longum has been shown to help reduce stress-related behaviors in dogs and cats.

1. Cryan, J. F., O’Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., …Dinan, T. G. (2019). The microbiota-gut-brain axis. Physiological Reviews, 99, 1877-2013. Doi: 10.1152/physrev.00018.2018
2. Kubinyi, E., Bel Rhali, S., Sándor, S., Szabó, A., & Felföldi, T. (2020). Gut microbiome composition is associated with age and memory performance in pet dogs. Animals, 10, 1488. doi: 10.3390/ani10091488
3. Sacoor, C., Marugg, J. D., Lima, N. R., Empadinhas, N., Montezinho, L. (2024). Gut-brain axis impact on canine anxiety disorders: New challenges for behavioral veterinary medicine. Hindawi Veterinary Medicine International, 2024, 2856759. doi: 10.1155/2024/2856759 
4. Sacchetino, L., Costanzo, M., Veneruso, I., D’Argenio, V., Mayer M, Napolitano, F., & d’Angelo, D. (2025). Altered microbiome and metabolome profiling in fearful companion dogs: An exploratory study. PLoS ONE, 20(1), e0315374. doi: 10.1371/journal.pone.0315374
5. Watanungura, A., Meller, S., Farhat, N., Suchodolski, J. S., Pilla, R., Khattab, M. R.,…Volk, H. A. (2024). Behavioral comorbidities treatment by fecal microbiota transplantation in canine epilepsy: A pilot study of a novel therapeutic approach. Frontiers in Veterinary Science, 11, 1385469. doi: 10.3389/fvets.2024.1385469
6. Ludvigsson, U., Heath, S., Tooley, C., Olmedal, G., Hellgren, J., Toni, M., & Toresson, L. (2026). Dogs with chronic enteropathy and low disease activity show signs consistent with compromised emotional health compared to matched healthy control dogs. Journal of the American Veterinary Medical Association, 264(7), 857-866. doi: 10.2460/javma.25.09.0623
7. Mills, D., Karagiannis, C., & Zulch, H. (2014). Stress – its effects on health and behavior: A guide for practitioners. Veterinary Clinics of North America: Small Animal Practice, 44, 525-541. doi: 10.1016/j.cvsm.2014.01.005
8. Kuntz, K., Ballantyne, K. C., Cousins, E., & Spitznagel, M. B. (2023). Assessment of caregiver burden in owners of dogs with behavioral problems and factors related to its presence. Journal of Veterinary Behavior, 64-65, 41-46. doi: 10.1016/j. jveb.2023.05.006
9. Coe, J. B., Young, I., Lambert, K., Dysart, L. Nogueira Borden, L., & Rajić, A. (2014). A scoping review of published research on the relinquishment of companion animals. Journal of Applied Animal Welfare Science, 17(3), 253-273. doi: 10.1080/10888705.2014.899910
10. Ballantyne, K. C. (2018). Separation, confinement, or noises: what is scaring that dog? Veterinary Clinics of North America: Small Animal Practice, 48(3), 367–386. doi:10.1016/j.cvsm.20112.005
11. Stelow, E. (2018). Diagnosing behavior problems: A guide for practitioners. Veterinary Clinics of North America, 48(3), 339–350. doi:10.1016/j.cvsm.2017.12.003
12. Mariti, C., Gazzano, A., Moore, J. L., Baragli, P., Chelli, L., & Sighieri, C. (2012). Perception of dogs’ stress by their owners. Journal of Veterinary Behavior, 7(4), 213–219.
13. Seibert, L. M., & Landsberg, G. M. (2008). Diagnosis and management of patients presenting with behavior problems. Veterinary Clinics of North America: Small Animal Practice, 38, 937–950.
14. Patronek, G. J., & Dodman, N. H. (1999). Attitudes, procedures, and delivery of behavior services by veterinarians in small animal practice. Journal of the American Veterinary Medical Association, 215(11), 1606–1611.
15. McGowan, R. T. S., Barnett, H. R., Czarnecki-Maulden, G. L., Si, X., Perez-Camargo, G., & Martin, F. (2018, July). Tapping into those ‘gut feelings’: Impact of BL999 (Bifidobacterium longum) on anxiety in dogs. Veterinary Behavior Symposium Proceedings, Denver, CO, pp. 8–9.
16. Davis H, Franco P, Gagné J, McGowan RTS, Hawley J, & Lappin M. (2021). Effect of Bifidobacterium longum 999 supplementation on stress associated findings in cats with FHV-1 infection (Abstract NM01). Presented at 2021 ACVIM Forum, abstract published in Journal of Veterinary Internal Medicine, 35(6), 3058. doi: 10.1111/jvim.16220