The educational content in this post, elaborated in collaboration with Bromatech, was independently developed and approved by the GMFH publishing team and editorial board.

The brain and gut talk to each other: scientists have made advances in understanding how that happens

While the language of the gut-brain axis is not new in our everyday work, it was not until recently that scientists started elucidating the mechanisms behind the gut-brain connection. Indeed, findings suggest the microbiome is an important regulator of said gut-brain axis, giving rise to proposals for a brain-gut-microbiota axis.

The gut microbiota and brain speak to each other constantly through three main pathways with different tempos:

  • The vagus nerve (neural pathway): this connects the visceral organs and the brain and is the fastest channel of communication for the gut microbiome to influence the brain.
  • Circulating hormones (endocrine pathway): they provide a slow and indirect communication route between the gut and brain.
  • Cytokines (immune pathway): in addition to suggestions that intestinal inflammation is involved in the development of neurodegenerative disorders, emerging evidence suggests that neuroinflammatory changes and altered microglia functions may involve the gut microbiome.

 

The gut microbiome profile provides clues for understanding several conditions not limited to the brain

Evidence for the influence of the gut microbiota on brain physiology comes mainly from germ-free animals. In addition, probiotic and antibiotic studies in mice and humans have shown the effects of the gut microbiota on behavior. However, that naturally occurring communication can be altered under stressful circumstances or brain disorders, as well as in the event of gastrointestinal disease.

“There are an ever-increasing number of conditions associated with dysregulation of the brain-gut-microbiota axis,” Prof. Ted Dinan told GMFH editors in an interview. “In psychiatry, depression and anxiety have been linked to disorders of the axis. There is also increasing evidence that obesity is a disorder of the brain-gut-microbiota axis.”

 

Examples of microbiome-based therapeutic interventions for mental health and brain disorders

Considering its influence of on brain physiology, the gut microbiota is now being targeted to mediate beneficial effects on brain health. In 2013, Dinan and colleagues first coined the term ‘psychobiotic’ as a “live organism that, when ingested in adequate amounts, produces a health benefit in patients suffering from psychiatric illness.” Since then, the definition has expanded to include other external means of influencing the brain through the microbiome.

Probiotics, prebiotics and fermented foods are the most widely studied potential psychobiotic therapies, with research undertaken mostly in healthy populations and through exploratory studies.

The brain-beneficial effects of probiotics are strain-dependent and have been shown in human studies reporting mostly indirect outcomes. Supplementation of pregnant women with Lactobacillus rhamnosus HN001 has been shown to decrease depression and anxiety scores in the postpartum period. Another promising strain that has been shown to abrogate stress in healthy volunteers is Bifidobacterium longum 1714.

Probiotics administered in the form of fermented foods have also been shown to impact brain physiology. The daily consumption of a fermented milk containing Lactobacillus casei strain Shirota prevented the onset of physical symptoms in medical students under academic examination stress. Another small study showed that the intake of a probiotic fermented milk reduced the reactivity of brain regions to an emotional attention task in healthy women.

Specific prebiotics have also shown benefits in disorders relating to the microbiota-gut-brain axis. A treatment combination of fructooligosacharides and galactooligosacharides exhibited antidepressant and anxiolytic effects in mice. Similarly, targeting the gut microbiome with the prebiotic oligofructose-enriched inulin reversed stress-induced immune priming and microglia activation in middle-aged mice. Other findings in healthy females showed that dietary fiber polydextrose resulted in modest improvement in cognitive performance.

 

Take-home messages

  • Direct and indirect pathways by which the gut microbiota can modulate the gut-brain axis include endocrine, immune and neural pathways.
  • An altered gut microbial profile has been found in neurodegenerative conditions and also those apparently not connected to the gut, such as obesity.
  • Specific probiotic strains and prebiotics emerge as novel potential strategies for the amelioration of age-related neuroinflammatory pathologies and brain function.

 

The Gut Microbiota for Health team interviewed Prof. Ted Dinan from University College Cork on evidence for the influence of the gut microbiota on brain and behavior and potential gut microbiome-targeted interventions with benefits for mental health:




 

 

References:

Cryan JF, O’Riordan KJ, Cowan CSM, et al. The microbiota-gut-brain axis. Physiol Rev. 2019; 99(4):1877-2013. https://doi.org/10.1152/physrev.00018.2018.

Fülling C, Dinan TG, Cryan JF. Gut microbe to brain signaling: what happens in vagus… Neuron. 2019; 101(6):998-1002. https://doi.org/10.1016/j.neuron.2019.02.008.

Houser MC, Tansey MG. The gut-brain axis: is intestinal inflammation a silent driver of Parkinson’s disease pathogenesis? NPJ Parkinsons Dis. 2017; 3:3. https://doi.org/10.1038/s41531-016-0002-0.

Bairamian D, Sha S, Rolhion N, et al. Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease. Mol Neurodegener. 2022; 17(1):19. https://doi.org/10.1186/s13024-022-00522-2.

Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012; 13(10):701-12. https://doi.org/10.1038/nrn3346.

Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel class of psychotropic. Biol Psychiatry. 2013; 74(10):720-6. https://doi.org/10.1016/j.biopsych.2013.05.001.

Long-Smith C, O’Riordan KJ, Clarke G, et al. Microbiota-gut-brain axis: new therapeutic opportunities. Annu Rev Pharmacol Toxicol. 2020; 60:477-502. https://doi.org/10.1146/annurev-pharmtox-010919-023628.

Slykerman RF, Hood F, Wickens K, et al. Effect of Lactobacillus rhamnosus HN001 in pregnancy on postpartum symptoms of depression and anxiety: a randomised double-blind placebo-controlled trial. EBioMedicine. 2017; 24:159-165. https://doi.org/10.1016/j.ebiom.2017.09.013.

Kato-Kataoka A, Nishida K, Takada M, et al. Fermented milk containing Lactobacillus casei strain Shirota prevents the onset of physical symptoms in medical students under academic examination stress. Benef Microbes. 2016; 7(2):153-6. https://doi.org/10.3920/BM2015.0100.

Tillisch K, Labus J, Kilpatrick L, et al. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology. 2013; 144(7):1394-401. https://doi.org/10.1053/j.gastro.2013.02.043.

Burokas A, Arboleya S, Moloney RD, et al. Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biol Psychiatry. 2017; 82(7):472-87. https://doi.org/10.1016/j.biopsych.2016.12.031.

Boehme M, van de Wouw M, Bastiaanssen TFS, et al. Mid-life microbiota crises: middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiome. Mol Psychiatry. 2020; 25(10):2567-83. https://doi.org/10.1038/s41380-019-0425-1.

Berding K, Long-Smith CM, Carbia C, et al. A specific dietary fibre supplementation improves cognitive performance-an exploratory randomised, placebo-controlled, crossover study. Psychopharmacology. 2021; 238(1):149-63. https://doi.org/10.1007/s00213-020-05665-y.