The Link Between Gut Microbes and Your Pet's Brain

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It might seem like your pet is led by their stomach: begging at the table for bits of food and always eager for treats. Researchers are discovering that the idea might not be that far off for certain behavior.

Animals are swarming with good bacteria, viruses, and other microorganisms that keep them healthy. Microbes, particularly those in the gut microbiome, help digest nutrients and protect against pathogens. Studies suggest that gut microbes can influence allergies, intestinal disease, or even cancer. And now links between the brain and the gut are coming to light, hinting that the bacterial contents of your pet's intestines could influence their aggression and anxiety.

Gut Microbes & the Brain

The brain has an intricate network designed to control and communicate with an animal’s body. Signals travel from the brain to initiate functions such as movement or emotion. And they also travel to the brain to simulate sensations, such as touch, sight or hearing.

Evidence has surfaced that suggests signals to the brain can originate from the gut1.

In general, bacteria consume nutrients, and they release chemicals into their environment. They might release things like a by-product of a processed nutrient — such as short-chain fatty acids from fiber2 — or a toxin designed to kill competing microbes. Some of these chemicals, however, are compounds that can have effects on the brain.

Dopamine, serotonin, and GABA, for instance, are chemical messengers called neurotransmitters that control animal brains3. Dopamine is often referred to as the “feel-good hormone,” because of its well-studied role in reward-motivated behavior. GABA, on the other hand, blocks signals between neurons and represses the activity of other neurotransmitters.

Scientists have long known that bacteria produced some of these compounds4. But researchers did not understand what that meant in the context of the brain until 2004, when a study was published showing that bacteria might be related to stress and anxiety in mice5.

The team looked at germ-free mice — which are completely free of microbes — and found that they had stronger responses to stress than mice that still had bacteria in their guts. But these differences disappeared when the researchers put certain bacteria in the intestines of germ-free mice.

Could this mean that the bacteria were somehow linked to stress in the mice? Could gut bacteria affect mental health?

From Mice to Humans to Pets

In the years since, researchers have been exploring the potential link between gut microbes and the brain, called the gut-brain axis. Anxiety, depression, Alzheimer’s disease, autism, behavior, fatigue, and mood are just some of the myriad disorders and mental states that appear to be connected to bacterial companions in the gut1,6.

Animal models provide the bulk of the evidence. Germ-free mice, for instance, have been instrumental in tying anxiety-like and depressive-like behaviors to gut microbes7. One study found that germ-free mice were less anxious than those that had a gut microbiome8. Others have shown that neonatal stress in rats has a long-term impact on the gut microbiome, and this changed their response to stress later in life9,10.

Studies have now been done in humans as well and found similar links among gut microbes and neurological disorders11. For example, people who had their vagus nerve — a key nerve in the central nervous system’s control over the digestive tract — cut at a young age had a lower risk of Parkinson’s disease12. But scientists still don’t fully understand how the gut microbiome interacts with the brain. Microbes appear to communicate with the brain through various metabolites, components of the immune system and the vagus nerve11. Even gut cells themselves have been identified that have a direct line to the brain via the vagus nerve13. And stimulating the vagus nerve is rewarding for the brain, which can treat depression14. Researchers don’t yet know whether gut bacteria have a direct impact on the brain — and cross the blood-brain barrier — or if they are missing another key piece to the puzzle.

Recently, some evidence for the same thing occurring has emerged in pets. A study published in PeerJ found that pitbulls seized from a dogfighting organization were more likely to be aggressive based on their gut microbiomes15. The researchers looked at the gut bacteria from 31 dogs, 21 of which displayed aggression toward other dogs and 10 which did not. They discovered some bacteria were lower in aggressive dogs, such as Bacteroides and Dorea, and some were elevated, such as Lactobacillus. The genus Fusobacterium was higher in non-aggressive dogs.

While the sample size is somewhat small, the data suggest that gut microbes are linked to canine aggression and could help to diagnose canine aggression before it becomes a problem. Exactly how the bacteria might contribute to aggression is unclear, since the study relied on 16S sequencing. Future studies can help corroborate the findings and begin to explore specific roles for various species.

Manipulating the Gut Microbiome

Just as probiotics could help with digestive health, scientists are exploring whether something similar could be used for diseases linked to the gut-brain axis16. Introducing bacteria, called psychobiotics, into the gut to help alleviate symptoms might help treat people (or pets) with anxiety or depression. For instance, studies have shown that giving Lactobacillus rhamnosus or Bacteroides fragilis to mice can decrease anxiety-like behavior17,18. Human research, too, has found that probiotics enhance mood19. Those who drank milk with Lactobacillus casei reported that their mood had improved at the end of the trial. While mood is not a medical condition, such studies provide a foundation for researchers to ask new questions about moving forward with possible treatments for depression and anxiety.

When combined with the knowledge that bacteria produce chemicals that can have effects on the brain16, it’s possible that psychobiotics could be a novel way to improve mental health. And as scientists learn more about the links between gut microbes and the brain, psychobiotics are sure to improve.

Closing Remarks

Many of the links between the brain and gut microbiomes are preliminary, but the idea still presents a fascinating avenue of research. Could we manipulate the gut microbiome to treat depression and anxiety? Can your pet’s behavior improve with the use of targeted psychobiotics? These are some of the questions microbiologists are striving to answer.



References

1. Lerner, A., Neidhöfer, S. & Matthias, T. The Gut Microbiome Feelings of the Brain: A Perspective for Non-Microbiologists. Microorganisms. 5, (2017).
2. Andoh, A., Tsujikawa, T. & Fujiyama, Y. Role of dietary fiber and short-chain fatty acids in the colon. Curr. Pharm. Des. 9, 347–358 (2003).
3. Strandwitz, P. Neurotransmitter modulation by the gut microbiota. Brain Res. 1693, 128–133 (2018).
4. Minuk, G. Y. Gamma-aminobutyric acid (GABA) production by eight common bacterial pathogens. Scand. J. Infect. Dis. 18, 465–467 (1986).
5. Sudo, N. et al. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J. Physiol. 558, 263–275 (2004).
6. Martin, C. R., Osadchiy, V., Kalani, A. & Mayer, E. A. The Brain-Gut-Microbiome Axis. Cell Mol Gastroenterol Hepatol. 6, 133–148 (2018).
7. Foster, J. A. & McVey Neufeld, K.-A. Gut-brain axis: how the microbiome influences anxiety and depression. Trends Neurosci. 36, 305–312 (2013).
8. Neufeld, K. M., Kang, N., Bienenstock, J. & Foster, J. A. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol. Motil. 23, 255–64, e119 (2011).
9. García-Ródenas, C. L. et al. Nutritional approach to restore impaired intestinal barrier function and growth after neonatal stress in rats. J. Pediatr. Gastroenterol. Nutr. 43, 16–24 (2006).
10. O’Mahony, S. M. et al. Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol. Psychiatry. 65, 263–267 (2009).
11. Dinan, T. G. & Cryan, J. F. The Microbiome-Gut-Brain Axis in Health and Disease. Gastroenterol. Clin. North Am. 46, 77–89 (2017).
12. Svensson, E. et al. Vagotomy and subsequent risk of Parkinson’s disease. Ann. Neurol. 78, 522–529 (2015).
13. Kaelberer, M. M. et al. A gut-brain neural circuit for nutrient sensory transduction. Science 361, (2018).
14. Han, W. et al. A Neural Circuit for Gut-Induced Reward. Cell. 175, 887–888 (2018).
15. Kirchoff, N. S., Udell, M. A. R. & Sharpton, T. J. The gut microbiome correlates with conspecific aggression in a small population of rescued dogs (Canis familiaris). PeerJ 7, e6103 (2019).
16. Sarkar, A. et al. Psychobiotics and the Manipulation of Bacteria-Gut-Brain Signals. Trends Neurosci. 39, 763–781 (2016).
17. Bravo, J. A. et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc. Natl. Acad. Sci. U. S. A. 108, 16050–16055 (2011).
18. Hsiao, E. Y. et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 155, 1451–1463 (2013).
19. Benton, D., Williams, C. & Brown, A. Impact of consuming a milk drink containing a probiotic on mood and cognition. Eur. J. Clin. Nutr. 61, 355–361 (2007).


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