The link between gut microbiome and behavior in dogs

Sponsored by Hill's Pet Nutrition

Intended for a veterinary professional audience

Recent research in veterinary medicine has illuminated a fascinating area of study: the connection between the gut microbiome and behavior in dogs. The gut microbiome is composed of a diverse population of microorganisms, including bacteria, archaea, viruses, and fungi, that reside in an animal’s digestive tract. These microorganisms are pivotal in various bodily functions, such as digestion, immune system modulation, and the production of essential vitamins and metabolites. Some of these metabolites include neurotransmitters like ɣ-aminobutyric acid (GABA), serotonin, melatonin, histamine, dopamine, acetylcholine, and norepinephrine.^1,2 This intricate relationship between the gut and the brain, known as the gut-brain axis, opens a new avenue for understanding cognitive and behavioral health in dogs.

The gut-brain axis

The gut-brain axis, a bidirectional communication system between the gastrointestinal (GI) tract and the brain, is a focal point of this burgeoning field. This connection is composed of neuronal, immune, metabolic, and endocrine system mediators.³ Multiple studies in rodents indicate that brain development can be influenced by the gut microbiome.^4-6 The gut-brain axis involves numerous pathways, as follows:

• Neural pathways: The vagus nerve is a primary component of the gut-brain axis. It facilitates direct communication between the gut and the brain, allowing for signaling that influences both GI and neurological functions.⁷
• Biochemical pathways: Microbial metabolites such as short-chain fatty acids (SCFAs) can cross the blood-brain barrier (BBB) and influence brain function.⁸ Neurotransmitters such as serotonin, produced in the gut, also play a role.⁹
• Immune pathways: The gut flora modulates the local and systemic immune systems, impacting brain health through neuroinflammatory responses.¹⁰

The microbiome’s influence on canine cognition

In dogs, like in humans, cognitive functions encompass processes like learning, memory, and problem-solving. Research indicates that the composition of the gut microbiome can influence these cognitive abilities through multiple pathways.

Neurotransmitters

The gut microbiome produces neurotransmitters and neuroactive compounds like serotonin, dopamine, and GABA.¹¹ These compounds are crucial for maintaining normal sleep, mood, cognition, anxiety levels, reward behaviors, and motivation.¹¹

Serotonin is synthesized from L-tryptophan and is primarily produced in the gut and the neurons of the enteric nervous system.¹² Microbial strains such as Candida, Streptococcus, Escherichia, and Enterococcus can regulate its synthesis.¹³

Dopamine is also produced and stored in the intestinal tract.¹⁴ Strains of Bacillus bacteria play a role in the regulation of dopamine.¹³ Dopamine is also a precursor to norepinephrine^,15 which is part of the sympathetic nervous system and involved in the fight-or-flight response. Norepinephrine can also be synthesized by the bacteria Escherichia, Bacillus, and Saccharomyces.¹³

GABA is a neurotransmitter that reduces neuronal excitability by inhibiting nerve transmission in both the central and enteric nervous systems.¹⁶ GABA can naturally be synthesized by lactic acid–producing bacteria, including the Lactobacillus, Enterococcus, Leuconostoc, Pediococcus, Propionibacterium, and Weissella genera.¹⁷ GABAergic neurotransmission plays a vital role in inhibiting the amygdala, thereby preventing inappropriate emotional and behavioral responses.

Inflammation

The gut microbiota play a critical role in the development and function of the immune system. A balanced gut microbiome supports a healthy immune response, while dysbiosis, or microbial imbalance, can lead to chronic inflammation. This inflammation impacts the central nervous system through the gut-brain axis, potentially altering neurotransmitter function and affecting behavior. For instance, elevated levels of proinflammatory cytokines have been linked to aggression in dogs.¹⁸

The hypothalamic-pituitary-adrenal (HPA) axis

The HPA axis plays a critical role in regulating stress responses and behavior in dogs.¹⁹ This complex system involves the interaction among the hypothalamus, pituitary gland, and adrenal glands, which collectively manage the release of cortisol, a key stress hormone. Activation of the HPA axis in response to stressors results in increased cortisol levels, which can influence various behavioral outcomes. For instance, chronic activation of the HPA axis, often seen in dogs experiencing prolonged stress or anxiety, can lead to behaviors such as aggressiveness.^20,21

Microbial metabolites

The gut microbiota produce multiple metabolites that play important roles in overall health and well-being. SCFAs such as butyrate, acetate, and propionate are an example of a class of these metabolites. SCFAs are energy sources for colonic epithelial cells and have anti-inflammatory, antiobesity, anticancer, antidiabetes, immunoregulatory, hepatoprotective, and cardiovascular protective effects.²²

GI dysbiosis can lead to altered production of SCFAs.²³ This dysbiosis can lead to an increased production of inflammatory cytokines and disruption of the intestinal barrier, which can lead to translocation of bacterial products and affect the BBB.²⁴ SCFAs also play a role in the communication between the GI tract and the brain. They regulate microglia functions and BBB integrity. Though there are no current studies that directly investigate the correlation between SCFAs and behavior in dogs, rodents supplemented with butyrate and other SCFAs had improvements in stress behaviors.²⁵

Practical applications

For veterinary practitioners, these findings have practical implications for both preventive care and therapeutic strategies, as follows:

• Diet and nutrition: Promoting balanced nutrition that supports gut health can be crucial. Foods rich in prebiotics can enhance beneficial bacterial metabolite production. Dogs fed a food containing prebiotic fibers and fish oil had a change in their microbiome composition and a significant decrease in plasma metabolites linked to anxiety behaviors.²⁶ Another study found that dogs with behavior disorders had significantly fewer inappropriate behaviors when supplemented with omega-3 fatty acids, magnesium, and zinc.²⁷ Providing these nutrients in the diet could have significant effects on the management of canine behavioral disorders.
• Probiotics and supplements: Fourteen days of supplementation of Lactiplantibacillus plantarum PS128 appeared to improve aggression and separation anxiety behaviors in dogs.²⁸ The same study found that plasma serotonin turnover ratio in dogs with separation anxiety was decreased after supplementation. A double-blind, placebo-controlled clinical trial explored the effects of a supplement comprised of prebiotics, probiotics, postbiotics, 5-hydroxytryptophan (serotonin precursor), L-theanine (GABA precursor), and other natural anti-inflammatory compounds.²⁹ Anxious dogs treated with this nutraceutical supplement demonstrated fewer anxiety-like behaviors, providing a promising direction for future studies.
• Fecal microbiota transplant: In dogs with idiopathic epilepsy and comorbid behavioral disorders, a fecal microbiota transplant improved fearlike, anxiety-like, and ADHD-like behaviors.³⁰ Even though this study had only 9 participants, this opens up the potential for new treatments for canine behavioral disorders in the future.

Conclusion

The influence of gut microbiota and gut-brain axis on mental and behavioral disorders is just beginning to be unraveled. The gut-brain axis is both bidirectional and multimodal, providing multiple opportunities for research and intervention. While current research offers exciting insights, further studies are needed to fully understand the mechanisms behind the gut-brain axis in dogs. Future research will be pivotal in harnessing the potential of the gut-brain axis for improving canine mental health and behavior.

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