The Gut-Brain Axis—Using the Brain and the Gut to Decide
World Small Animal Veterinary Association Congress Proceedings, 2019
C. Siracusa
Clinical Sciences and Advanced Medicine, Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA


The reciprocal link between behavior and the inflammatory and immune response has been extensively documented in the scientific literature. This reciprocal interaction between the immune system and behavior is also influenced by the host microbiome (i.e., the skin and gut microbiome).1,2 Activation of proinflammatory cytokines induces a depressed state (sickness), which helps the individual to cope with the disease (e.g., an infection by exogenous pathogens) that triggered the inflammatory response. Circulating proinflammatory cytokines can enter the brain, where they have a direct inflammatory action and stimulate the production of other pro-inflammatory cytokines and prostaglandins. Although this inflammatory response does not produce tissue damage, it induces a negative behavioral change. Circulating proinflammatory cells also exercise their action on the brain indirectly through neuronal pathways, for example, activating a vagal response.1 The endogenous microorganisms constituting the intestinal microbiome may influence the behavior of their animal hosts through a similar action. The microbiota is capable of modulating the stress response via the HPA-axis, or directly through vagal neuronal stimulation, cytokine action, or modulation of metabolites with an inhibitory or excitatory action on the brain.2-5 An increasing body of evidence about the direct influence of the gut microbiome on behavior is being produced. In humans, butyrate producing Faecalibacterium and Coprococcus bacteria were consistently associated with higher quality of life indicators in a study. Dialister and Coprococcus spp. bacteria are depleted in people with depression,3 while-aminobutyric acid-modulating bacteria have a protective role against depression.3,4 GABA-modulating Bacteriodies bacteria are elevated in the gut microbiome of non-aggressive dogs, while Lactobacillus bacteria were more abundant in aggressive dogs.5 Chronic gastrointestinal conditions that alter the microbiota might therefore influence the behavior of an individual, beyond the changes associated with discomfort and nutritional compromise.

The link between the skin microbiome and the inflammatory and immune response has been documented,6,7 and chronic stress may play a role in the pathogenesis of dermatologic disease. However, the direct influence of the skin microbiome on behavior has not yet been determined.

In clinics, inflammation of both the gastrointestinal tract and the skin has been associated with abnormal repetitive behaviors. Inflammatory diseases of the gastrointestinal tract (eosinophilic and/or lymphoplasmacytic infiltration, irritable bowel syndrome, chronic pancreatitis, gastric foreign body, giardiasis) have been diagnosed in 74% of dogs presented for excessive licking.8 Inflammatory skin conditions (atopy, adverse food reactions, parasitic hypersensitivity) were detected in 90% of cats presented for self-induced alopecia.9 A protective action of probiotics and antioxidants has been suggested. Supplementing the diet of anxious dogs with Bifidobacterium longum BL999 resulted in a reduction of stress-related behaviors jumping, spinning, pacing, and barking, as well as in an increase of exploratory behavior. In addition, salivary cortisol decreased, and heart rate variability increased in dogs that received BL999.10


1.  Dantzer D, O’Connor JC, Freund GC, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008;9:46–56.

2.  Foster JA, McVey Neufeld K. Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 2013;36:305–312.

3.  Valles-Colomer M, Falony G, Darzi Y, et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol. 2019:4:623–632.

4.  Strandwitz P, Hyun Kim K, Terekhova D, et al. GABA-modulating bacteria of the human gut microbiota. Nat Microbiol. 2019;4:396–403.

5.  Kirchoff NS, Udell MA, Sharpton TJ. The gut microbiome correlates with conspecific aggression in a small population of rescued dogs (Canis familiaris). Peer J. 2019;7:e6103.

6.  Iwase T, Uehara Y, Shinji H, et al. Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization. Nature. 2010;465:346–349.

7.  Tlaskalová-Hogenová H, Stepánková R, Hudcovic T, et al. Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol Lett. 2004;93:97–108.

8.  Becuwe-Bonnet V, Belanger MC, Frank D, Parent J, Helie P. Gastrointestinal disorders in dogs with excessive licking of surfaces. J Vet Behav. 2012;7:194–204.

9.  Waisglass SE, Landsberg GM, Yager JA, Hall JA. 2006. Underlying medical conditions in cats with presumptive psychogenic alopecia. J Am Vet Med Assoc. 2006;228:1705–1709.

10.  McGowan RTS, Barnett HR, Czarnecki-Maulden G, Si X, Perez-Camargo G, Martin F. Tapping into those ‘gut feelings’: impact of BL999 (Bifidobacterium longum) on anxiety in dogs. In: Proceedings of the 2018 ACVB Veterinary Behavior Symposium, Denver, CO. American College of Veterinary Behaviorists, 2018.


Speaker Information
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C. Siracusa
Clinical Sciences and Advanced Medicine
Veterinary Medicine
University of Pennsylvania
Philadelphia, PA, USA

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