Psychobiotic diet & stress
22nd Nov, 2022


A recent study indicates that following a diet rich in prebiotic and fermented foods, termed a psychobiotic diet, can reduce stress and improve sleep (1).

Over the past decade, a growing body of research has shown that diet can significantly impact neurological function, cognition and mental health via processes involving the communication pathways between the gut microbiome and the brain (the microbiota–gut–brain axis) (2). These findings led to new research into microbiome-targeted therapies termed psychobiotics. These therapies have a bacterially mediated impact on the brain and behaviour and include prebiotics, probiotics, postbiotics  and dietary interventions (3,4,5).

Microorganisms can influence central nervous system (CNS) processes bidirectionally via the vagus nerve (6) and through modulation of the immune system (7), the hypothalamic-pituitary-adrenal (HPA) axis (8), and tryptophan metabolism, along with their ability to synthesise several neurotransmitters (9,10) and produce metabolites, such as short-chain fatty acids (SCFAs). Experimental studies suggest that these microbiota-mediated mechanisms could underlie the diet–brain connection (11). Human clinical studies have demonstrated the efficacy of microbiota-targeted dietary approaches, such as the Mediterranean diet, for improving mental health and cognition (12,13,14). However, the majority of these studies did not examine microbiota compositional changes, and further research is required to assess the association between diet, gut microbiome and mental health (15).


Figure 1. Action of mechanisms by which the gut microbiota exert the potential psychobiotic effect (11) CC BY 4.0

 Figure 1


In a recent four-week randomised controlled trial (RCT), 45 healthy adults aged 18 to 59 years were randomised into two groups: an intervention group that followed a psychobiotic diet and a control group that followed a diet based on the healthy eating food pyramid.

All participants consumed a low-fibre diet, with an average intake of less than 15 g/day, which is well below the recommended daily intake of 30/day for men and 25 g/day for women (16).

The psychobiotic diet included 6-8 servings daily of fruits and vegetables high in prebiotic fibres (such as onions, leeks, cabbage, apples, bananas and oats), 5-8 servings of grains per day, 3-4 servings of legumes per week and 2-3 servings of fermented foods daily (such as sauerkraut, kefir and kombucha).

Stress, overall health, sleep and diet were assessed using validated questionnaires. Results show that a psychobiotic diet significantly reduces stress. After one month, 32% of participants on the psychobiotic diet had reduced perceived stress scores, compared to only 17% of participants on the control diet. The reduction in perceived stress was dose-dependent, meaning that higher adherence to the psychobiotic diet resulted in greater decreases in stress scores. The quality of sleep improved in both groups; however, only participants on the psychobiotic diet had a statistically significant improvement in subjective sleep quality.

To assess the potential mechanisms underlying the microbiota-gut-brain communication, faecal, urinary and blood specimens were provided before and during the study. The faecal samples were analysed to determine microbiota composition and function. In addition, urinary and blood samples were analysed for key metabolites resulting from human-gut microbiota co-metabolism of dietary essential amino acids tryptophan, tyrosine, phenylalanine, and branched-chain amino acids.

Morning cortisol levels and inflammatory markers were not significantly affected by the psychobiotic dietary intervention, suggesting short-term dietary intervention did not alter perceived stress via effects on the immune system or HPA axis. In addition, microbiota composition and function did not significantly vary in the psychobiotic group, which may have been due to the short study duration.

Significant changes in the level of 40 specific faecal lipids were observed. Recent experimental studies have reported associations between changes in lipid metabolites, and depressive-like behaviour, suggesting that the microbiota might influence mood by regulating lipid metabolism (17,18).

In the psychobiotic dietary group, there was a significant decrease in urinary metabolites of quinolinic acid, L-tryptophan, and L-phenylalanine. Tryptophan is an essential amino acid required to produce melatonin, which helps regulate the sleep-wake cycle, and serotonin, a neurotransmitter that helps regulate appetite, mood, sleep, and pain. This amino acid can be metabolised in two pathways relevant to depression and other neuropsychiatric disorders: the serotonin and kynurenine pathways (19). In the current study, the psychobiotic diet reduced the kynurenine pathway metabolite, quinolinic acid. This metabolite is an N-methyl-d-aspartate (NMDA) receptor agonist and can exert neurotoxic effects, which can disrupt neurotransmission and cause depressive symptoms (20,21).

The study had several limitations, including the limited sample size, short study duration, and the use of food frequency questionnaires which are susceptible to measurement error and bias in estimating food intake. Nevertheless, the results suggest that dietary interventions targeting the gut microbiota can reduce stress and improve sleep, potentially through the effects on tryptophan metabolism and lipid metabolites. More extensive and longer-duration studies are warranted to confirm the stress-alleviating effect of the psychobiotic diet and identify the underlying mechanistic pathways.

1Berding K, Bastiaanssen TF, Moloney GM, Boscaini S, Strain CR, Anesi A, Long-Smith C, Mattivi F, Stanton C, Clarke G, Dinan TG. Feed your microbes to deal with stress: a psychobiotic diet impacts microbial stability and perceived stress in a healthy adult population. Molecular Psychiatry. 2022 Oct 27:1-0.
2Marx W, Lane M, Hockey M, Aslam H, Berk M, Walder K, Borsini A, Firth J, Pariante CM, Berding K, Cryan JF. Diet and depression: exploring the biological mechanisms of action. Molecular psychiatry. 2021 Jan;26(1):134-50.
3Bermúdez-Humarán LG, Salinas E, Ortiz GG, Ramirez-Jirano LJ, Morales JA, Bitzer-Quintero OK. From probiotics to psychobiotics: live beneficial bacteria which act on the brain-gut axis. Nutrients. 2019 Apr 20;11(4):890.
4Berding K, Cryan JF. Microbiota-targeted interventions for mental health. Current Opinion in Psychiatry. 2022 Jan;35(1):3.
5Cheng Y, Liu J, Ling Z. Short-chain fatty acids-producing probiotics: A novel source of psychobiotics. Critical Reviews in Food Science and Nutrition. 2022 Oct 3;62(28):7929-59.
6Bonaz B, Sinniger V, Pellissier S. The vagus nerve in the neuro-immune axis: implications in the pathology of the gastrointestinal tract. Frontiers in immunology. 2017 Nov 2;8:1452.
7Erny D, Hrabě de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, David E, Keren-Shaul H, Mahlakoiv T, Jakobshagen K, Buch T, Schwierzeck V. Host microbiota constantly control maturation and function of microglia in the CNS. Nature neuroscience. 2015 Jul;18(7):965-77.
8Misiak B, Łoniewski I, Marlicz W, Frydecka D, Szulc A, Rudzki L, Samochowiec J. The HPA axis dysregulation in severe mental illness: Can we shift the blame to gut microbiota?. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2020 Aug 30;102:109951.
9O’Mahony SM, Clarke G, Borre YE, Dinan TG, Cryan JF. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behavioural brain research. 2015 Jan 15;277:32-48.
10Gao K, Mu CL, Farzi A, Zhu WY. Tryptophan metabolism: a link between the gut microbiota and brain. Advances in Nutrition. 2020 May 1;11(3):709-23.
11Del Toro-Barbosa M, Hurtado-Romero A, Garcia-Amezquita LE, García-Cayuela T. Psychobiotics: mechanisms of action, evaluation methods and effectiveness in applications with food products. Nutrients. 2020 Dec 19;12(12):3896.
12Jacka FN, O’Neil A, Opie R, Itsiopoulos C, Cotton S, Mohebbi M, Castle D, Dash S, Mihalopoulos C, Chatterton ML, Brazionis L. A randomised controlled trial of dietary improvement for adults with major depression (the ‘SMILES’trial). BMC medicine. 2017 Dec;15(1):1-3.
13Esgunoglu L, Jennings A, Connole ES, Murphy KJ, Minihane AM. Short-term effects of a Mediterranean-style dietary pattern on cognition and mental wellbeing: A systematic review of clinical trials. Proceedings of the Nutrition Society. 2021;80(OCE3).
14Parletta N, Zarnowiecki D, Cho J, Wilson A, Bogomolova S, Villani A, Itsiopoulos C, Niyonsenga T, Blunden S, Meyer B, Segal L. A Mediterranean-style dietary intervention supplemented with fish oil improves diet quality and mental health in people with depression: A randomized controlled trial (HELFIMED). Nutritional neuroscience. 2019 Jul 3;22(7):474-87.
15Ribeiro G, Ferri A, Clarke G, Cryan JF. Diet and the microbiota–gut–brain-axis: a primer for clinical nutrition. Current Opinion in Clinical Nutrition and Metabolic Care. 2022 Nov 1;25(6):443-50.
16National Health and Medical Research Council. Nutrient Reference Values: Iron [Internet]. NHMRC. 2006 [cited 2022 November 17]. Available from:
17Gong X, Huang C, Yang X, Chen J, Pu J, He Y, Xie P. Altered Fecal Metabolites and Colonic Glycerophospholipids Were Associated With Abnormal Composition of Gut Microbiota in a Depression Model of Mice. Frontiers in Neuroscience. 2021:826.
18Jiang W, Gong L, Liu F, Ren Y, Mu J. Alteration of gut microbiome and correlated lipid metabolism in post-stroke depression. Frontiers in cellular and infection microbiology. 2021 Apr 22;11:663967.
19Comai S, Bertazzo A, Brughera M, Crotti S. Tryptophan in health and disease. Advances in clinical chemistry. 2020 Jan 1;95:165-218.
20Lugo-Huitrón R, Ugalde Muñiz P, Pineda B, Pedraza-Chaverrí J, Ríos C, Pérez-de la Cruz V. Quinolinic acid: an endogenous neurotoxin with multiple targets. Oxidative medicine and cellular longevity. 2013 Oct;2013.
21Hestad K, Alexander J, Rootwelt H, Aaseth JO. The Role of Tryptophan Dysmetabolism and Quinolinic Acid in Depressive and Neurodegenerative Diseases. Biomolecules. 2022 Jul 18;12(7):998.