Feed your microbes to improve gut and mental health

Why does the microbiota-gut-brain axis matter?

While the existence of a link between the gut and the brain has recently gained growing attention from the media, the concept of the gut-brain axis is not new. In the 19^th and 20^th centuries, work from different scientists and physicians, such as William Beumont, Charles Darwin, and Claude Bernard linked gut and digestion to emotions. Later on, studies suggested that the huge community of microorganisms living in the gut are important players in the gut-brain axis, which has led to the term ‘microbiota-gut-brain axis¹.

The microbiota-gut-brain axis consists of a diverse microbial community in the intestinal tract that communicates with the central nervous system and vice versa¹. Some disorders of mood and intestinal motility in which the gut-brain connection is altered include irritable bowel syndrome, depression, and anxiety^1,2. For instance, mental health disorders observed in one out of three patients with IBS have been suggested to be associated with the gut-brain axis.

How do your gut and brain ‘talk’ to each other?

Microbial metabolites that are anti-inflammatory (e.g. butyrate) or beneficially influence mental health (e.g. serotonin) represent just one means of communication between the gut and the brain.

The three other major routes through which gut microbes interact with the brain involve^2,3:

• The vagus nerve and enteric neurons act like your mobile phone, allowing quick and direct communication between the gut and the brain.
• Hormones (e.g., cortisol) act like postal mail, allowing slower communication between the gut and the brain.
• Small proteins released by immune cells (cytokines) act like alarm signals, allowing long-distance communication between cells.

How can you harness gut microbes for improving brain health?

Considering the role of the gut microbiota in mediating the beneficial effects of diet on the brain, Irish scientists have coined the term psychobiotic to describe any exogenous intervention that impacts the microbiome and benefits mental health^4-6.

Potential psychobiotic interventions that have shown promising results for improving mental health in both animal and human studies include:

1. Whole diet

A diet enriched with fiber and fermented foods promoting good bacteria in the gut (a “psychobiotic diet”) has beneficial effects on decreasing perceived stress levels in healthy volunteers after just one month⁷ and improving depressive mood in adults with obesity⁸.

Also, a Mediterranean diet rich in vegetables, fruit, whole grains, legumes, nuts and seeds, olive oil, and fish, and with small quantities of red meat and processed foods, would help alleviate depression and provide additional benefits to medication¹⁰ and may improve both gut and psychological symptoms in people with IBS^11,12.

Other diets, such as the Dietary Approaches to Stop Hypertension (DASH) diet, Norwegian diet, and Japanese diet have been linked to decreased prevalence of common mental diseases and improved cognitive performance^13-15.

In contrast, a Western diet rich in foods high in salt, sugar, and unhealthy fats is associated with a smaller hippocampus, an area of the brain related to learning and memory⁹.

2. Prebiotics

Most prebiotics are a type of dietary fiber that is food for beneficial microbes living on or in us. Beyond their benefits for digestive function and the body’s natural defenses, emerging evidence shows that prebiotics have positive effects on stress levels, mood, and cognitive function.

Supplementation with a galactooligosaccharide prebiotic may reduce waking cortisol response-the stress hormone linked to anxiety and depression- and anxiety levels in healthy volunteers^16,17. Similarly, two months supplementation with a galactooligosaccharide prebiotic reduced anxiety in people with IBS¹⁸. Polydextrose fiber may also improve cognitive flexibility and sustained attention in healthy individuals¹⁹.

3. Probiotics

Probiotics are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.” Emerging research suggests that, similar to prebiotics, probiotics could be an add-on intervention for the brain and well-being.

For instance, Bifidobacterium longum 1714 may decrease salivary cortisol and perceived stress and increase visual and spatial memory in healthy individuals^20,21. Lactobacillus plantarum PS128 may also reduce perceived stress, anxiety, and depression in highly stressed people²². Probiotic strains belonging to L. helveticus and B. longum may also decrease depression severity in patients with major depressive disorder²³.

4. Synbiotics

Mixtures comprising live microorganisms and substrate(s) selectively utilized by host microorganisms have also shown benefits in improving anxiety²⁴ and mild-to-moderate depression²⁵.

5. Fermented foods

Most studies on the impact of fermented foods on brain health have been done in mice²⁶. Small studies have shown the potential benefits of fermented milk drinks in reducing physical symptoms of stress and ameliorate increase in salivary cortisol²⁷ and impact immune cells²⁸ in students under examination stress and alter brain activity²⁹.

6. Postbiotics and microbial metabolites

Inanimate microorganisms and/or their components have shown potential benefits on the host. This is the case of heat-inactivated microbes that have shown some benefits in reducing anxiety as well as improving in sleep disturbance in chronically stressed students³⁰.

When it comes to microbial metabolites, while data showed that purified microbial metabolites such as short chain fatty acids attenuate depressive-like behaviours and cortisol stress response in rodents³¹, human data does not support yet the benefits of isolated metabolites such as butyrate for reducing stress³².

7. Fecal microbiota transplants

Based on the potential benefits for mental health of probiotics and prebiotics, scientists have also started exploring the role of fecal microbiota transplants (FMT) to treat brain-related disorders. While one human trial showed an improvement in quality of life fatigue after FMT in patients with IBS,³³ it is too early to known the efficacy of this procedure for improving anxiety, depression, and other neuroinflammation-related disorders. It is also important to balance the benefits with the risks involving safety issues and the transfer of diseases that involve the microbiome³¹.

Are there non-dietary alternatives for improving gut and brain health?

Beyond diet and lifestyle changes, psychological therapies are also worth considering for reducing gut symptoms and lessening the psychological sequelae of IBS and IBD³⁴.

Interventions studied to improve and maintain gut and mental health involve psychological therapies (cognitive behavioural therapy and gut-directed hypnotherapy), stress management (mindfulness-based therapies, yoga), sleep and rest, regular light-to-moderate exercise, and outdoor activities in nature. These interventions could be valuable when dietary approaches are difficult to implement or as an adjunctive approach.

Bottom line

• Good physical and mental health can support your gut health. In the other direction this is also true, as a good status of the gut microbiota is important for your mental health.
• Potential psychobiotic interventions that have shown promising results for improving mental health through impacting your microbiome include a diet high in fiber-rich foods and fermented foods, probiotics, prebiotics, synbiotics, and postbiotics.
• Beyond diet, psychological therapies, exercise, resting, and spending time in nature may help improve gut health, stress, mental health, and quality of life.

References:

1. Cryan JF, O’Riordan KJ, Cowan CSM, et al. The microbiota-gut-brain axis. Physiol Rev. 2019; 99(4):1877-2013. doi: 10.1152/physrev.00018.2018.
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. doi: 10.1038/nrn3346.
3. Marx W, Lane M, Hockey M, et al. Diet and depression: exploring the biological mechanisms of action. Mol Psychiatry. 2021; 26(1):134-150. doi: 10.1038/s41380-020-00925-x.
4. Marx W, Moseley G, Berk M, et al. Nutritional psychiatry: the present state of the evidence. Proc Nutr Soc. 2017; 76(4):427-436. doi: 10.1017/S0029665117002026.
5. Dinan TG, Stanton C, Cryan JF. Psychobiotics: a novel class of psychotropic. Biol Psychiatry. 2013; 74(10):720-6. doi: 10.1016/j.biopsych.2013.05.001.
6. Sarkar A, Lehto SM, Harty S, et al. Psychobiotics and the manipulation of bacteria-gut-brain signals. Trends Neurosci. 2016; 39(11):763-781. doi: 10.1016/j.tins.2016.09.002.
7. Berding K, Bastiaanssen TFS, Moloney GM, et al. Feed your microbes to deal with stress: a psychobiotic diet impacts microbial stability and perceived stress in a healthy adult population. Mol Psychiatry. 2022; 28(2):601-610. doi: 10.1038/s41380-022-01817-y.
8. Uemura M, Hayashi F, Ishioka K, et al. Obesity and mental health improvement following nutritional education focusing on gut microbiota composition in Japanese women: a randomised controlled trial. Eur J Nutr. 2019; 58(8):3291-3302. doi: 10.1007/s00394-018-1873-0.
9. Jacka FN, Cherbuin N, Anstey KJ, et al. Western diet is associated with a smaller hippocampus: a longitudinal investigation. BMC Med. 2015; 13:215. doi: 10.1186/s12916-015-0461-x.
10. Jacka FN, O’Neil A, Opie R, et al. A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial). BMC Med. 2017; 15(1):23. doi: 10.1186/s12916-017-0791-y.
11. Staudacher HM, Mahoney S, Canale K, et al. Clinical trial: A Mediterranean diet is feasible and improves gastrointestinal and psychological symptoms in irritable bowel syndrome. Aliment Pharmacol Ther. 2024; 59(4):492-503. doi: 10.1111/apt.17791.
12. Staudacher HM, Black CJ, Teasdale SB, et al. Irritable bowel syndrome and mental health comorbidity – approach to multidisciplinary management. Nat Rev Gastroenterol Hepatol. 2023; 20(9):582-596. doi: 10.1038/s41575-023-00794-z.
13. Opie RS, Itsiopoulos C, Parletta N, et al. Dietary recommendations for the prevention of depression. Nutr Neurosci. 2017; 20(3):161-171. doi: 10.1179/1476830515Y.0000000043.
14. Nanri A, Kimura Y, Matsushita Y, et al. Dietary patterns and depressive symptoms among Japanese men and women. Eur J Clin Nutr. 2010; 64(8):832-9. doi: 10.1038/ejcn.2010.86.
15. Staudacher HM, Teasdale S, Cowan C, et al. Chapter 5 – Diet Interventions for Anxiety and Depression. In: Dinan T, ed. Nutritional Psychiatry. A Primer for Clinicians. Cambridge: Cambridge University Press; 2023. pp. 72-100.
16. Schmidt K, Cowen PJ, Harmer CJ, et al. Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology (Berl). 2015; 232(10):1793-801. doi: 10.1007/s00213-014-3810-0.
17. Johnstone N, Milesi C, Burn O, et al. Anxiolytic effects of a galacto-oligosaccharides prebiotic in healthy females (18-25 years) with corresponding changes in gut bacterial composition. Sci Rep. 2021; 11(1):8302. doi: 10.1038/s41598-021-87865-w.
18. Silk DBA, Davis A, Vulevic J, et al. Clinical trial: the effects of a trans-galactooligosaccharide prebiotic on faecal microbiota and symptoms in irritable bowel syndrome. Aliment Pharmacol Ther. 2009; 29(5):508-18. doi: 10.1111/j.1365-2036.2008.03911.x.
19. Berding K, Long-Smith CM, Carbia C, et al. A specific dietary fibre supplementation improves cognitive performance-an exploratory randomized, placebo-controlled, crossover study. Psychopharmacology (Berl). 2021; 238(1):149-163. doi: 10.1007/s00213-020-05665-y.
20. Allen AP, Hutch W, Borre YE, et al. Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers. Transl Psychiatry. 2016; 6(11)e939. doi: 10.1038/tp.2016.191.
21. Wang H, Braun C, Murphy EF, et al. Bifidobacterium longum 1714^TM strain modulates brain activity of healthy volunteers during social stress. Am J Gastroenterol. 2019; 114(7):1152-1162. doi: 10.14309/ajg.0000000000000203.
22. Wu SI, Wu CC, Tsai PJ, et al. Psychobiotic supplementation of PS128^TM improves stress, anxiety, and insomnia in highly stressed information technology specialists: a pilot study. Front Nutr. 2021; 8:614105. doi: 10.3389/fnut.2021.614105.
23. Kazemi A, Noorbala AA, Azam K, et al. Effect of probiotic and prebiotic vs placebo on psychological outcomes in patients with major depressive disorder: a randomized clinical trial. Clin Nutr. 2019; 38(2):522-528. doi: 10.1016/j.clnu.2018.04.010.
24. Zhao Z, Xiao G, Xia J, et al. Effectiveness of probiotic/prebiotic/synbiotic treatments on anxiety: A systematic review and meta-analysis of randomized controlled trials. J Affect Disord. 2023; 343:9-21. doi: 10.1016/j.jad.2023.09.018.
25. Zhang Q, Chen B, Zhang J, et al. Effect of prebiotics, probiotics, synbiotics on depression: results from a meta-analysis. BMC Psychiatry. 2023; 23(1):477. doi: 10.1186/s12888-023-04963-x.
26. Balasubramanian R, Schneider E, Gunnigle E, et al. Fermented foods: Harnessing their potential to modulate the microbiota-gut-brain axis for mental health. Neurosci Biobehav Rev. 2024; 158:105562. doi: 10.1016/j.neubiorev.2024.105562.
27. 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. doi: 10.3920/BM2015.0100.
28. Marcos A, Wärnberg J, Nova E, et al. The effect of milk fermented by yogurt cultures plus Lactobacillus casei DN-114001 on the immune response of subjects under academic examination stress. Eur J Nutr. 2004; 43(6):381-9. doi: 10.1007/s00394-004-0517-8.
29. Tillisch K, Labus J, Kilpatrick L, et al. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology. 2013; 144(7):1394-401. doi: 10.1053/j.gastro.2013.02.043.
30. Nishida K, Sawada D, Kuwano Y, et al. Health benefits of Lactobacillus gasseri CP2305 tablets in young adults exposed to chronic stress: a randomized, double-blind, placebo-controlled study. Nutrients. 2019; 11(8):1859. doi: 10.3390/nu11081859.
31. Berding K, Cryan JF. Microbiota-targeted interventions for mental health. Curr Opin Psychiatry. 2022; 35(1):3-9. doi: 10.1097/YCO.0000000000000758.
32. Dalile B, Fuchs A, La Torre D, et al. Colonic butyrate administration modulates fear memory but not the acute stress response in men: A randomized, triple-blind, placebo-controlled trial. Prog Neuropsychopharmacol Biol Psychiatry. 2024. doi: 10.1016/j.pnpbp.2024.110939.
33. Johnsen PH, Hilpüsch F, Christian Valle P, et al. The effect of fecal microbiota transplantation on IBS related quality of life and fatigue in moderate to severe non-constipated irritable bowel: Secondary endpoints of a double blind, randomized, placebo-controlled trial. EBioMedicine. 2020; 51:102562. doi: 10.1016/j.ebiom.2019.11.023.
34. Loughman A, Staudacher HM. How can I improve my gut health via non-dietary means? Lancet Gastroenterol Hepatol. 2024; 9(1):20. doi: 10.1016/S2468-1253(23)00412-0.