The Emerging Axis: How Gut Microbiota Shape the Landscape of Mental Disorders

By Martina Bruno, Product Manager, SynBalance Probiotics & Silvia Castegnaro, Marketing Manager, SynBalance Probiotics

The human gastrointestinal tract is home to a complex and highly populated microbial ecosystem, known as the gut microbiota. Including trillions of microorganisms, such as bacteria, viruses, and fungi, this microbial community plays a crucial role in maintaining host homeostasis. In recent years, increasing evidence has highlighted the influence of the gut microbiota on brain function, particularly regarding mood and behavior (1), (2).

Central to this interaction is the gut-brain axis, a complex and bidirectional network that connects the gastrointestinal tract and the central nervous system through neural, endocrine, and immune pathways (3). At the core of this axis lies the ability of the gut microbiota to produce and modulate neurotransmitters like serotonin, dopamine, and gamma-aminobutyric acid (GABA), as well as the numerous signal molecules involved in the immune response, such as cytokines (e.g. IL-6, TNF-α) and chemokines. Notably, serotonin’s production occurs mainly in the enterochromaffin cells of the gut and its synthesis is strongly influenced by the microbial metabolism of tryptophan, its precursor. Several probiotics strains have been shown to increase peripheral tryptophan levels, promoting its conversion to serotonin rather than to kynurenine, a metabolite implicated in depression and autism spectrum disorders (ASD) (4). Similarly, the gut microbiota contributes to the biosynthesis and availability of dopamine and its precursors, which are known to affect reward processing, motivation, and executive function (5). Several gut microbes also produce GABA, the primary inhibition neurotransmitter in the brain, with implications for anxiety and mood regulation. Beyond neurotransmitters, gut bacteria are also able to secrete metabolites called short-chain fatty acids (SCFAs) that can cross the blood-brain barrier and exert neuroactive effects (6).

A key conduit for gut-brain communication is the vagus nerve, which transmits gut-generated signals to the brain. In addition, gut dysbiosis, an imbalance in the gut microbiota, has been linked to the activation of systemic immune responses and inflammatory pathways, associated with numerous psychiatric disorders, such as major depressive disorders and generalized anxiety disorders (7). Indirectly, the gut microbiota also modulates brain function by influencing immune cell activity through cytokines release, increasing intestinal permeability (leaky gut) therefore promoting systemic inflammation, and altering the secretion of gut-derived hormones such as ghrelin and GLP-1, which are known to affect mood and cognitive function, further contributing to the development and progression of mental issues (8).

Probiotics have shown potential in improving mood and mental health by restoring the balance of gut microbiota, reducing inflammation, and enhancing neurotransmitter production. This role has been mainly observed in conditions such as depression, schizophrenia, autism spectrum disorder (ASD), and bipolar disorder (9).

Depression is one of the most prevalent and disabling mental health conditions worldwide, affecting nearly 300 million people (10), therefore it is also one of the most studied condition in relation to probiotics. A meta-analysis showed that probiotics supplementation has been associated with a significant reduction in depression scores as measured by the Hamilton Depression Rating Scale (Weighted Mean Difference: -9.60; 95 % CI: -10.08, -9.11) and biomarkers of inflammation, which are often elevated in depressive disorders. In particular, probiotics contributed to significantly reducing the levels of C-reactive protein (WMD: -1.59; 95 % CI: -2.22, -0.97), Tumor Necrosis Factor-alpha (TNF-α) (WMD: -0.12; 95 % CI: -0.20, -0.05) and Interleukin-10 (WMD: -0.29; 95 % CI: -0.48, -0.11) (11). By counteracting processes such as low-grade systemic inflammation, dysregulation of neurotransmitters, and disrupted tryptophan metabolism, specific strains of bacteria can exert anti-depressive effects, reducing the severity of depressive symptoms (12).

In addition to depression, probiotics might also contribute to managing symptoms in ASD and schizophrenia. ASD is a complex neurodevelopmental condition characterized by social deficits, repetitive behaviors, and impaired communication, and it is often linked to gastrointestinal disturbances and unbalanced gut microbiota. In these cases, the intake of probiotics has been proven to alleviate gastrointestinal symptoms (as assessed by the six-item Gastrointestinal Severity Index 6-GSI) and sometimes even reduce behavioral abnormalities, suggesting a beneficial effect on both physical and cognitive symptoms (as assessed by the Autism Treatment Evaluation Checklist) (13).

Although research on probiotics in schizophrenia and bipolar disorder is still emerging, early studies have suggested similar benefits. In fact, these disorders have also been linked to gut dysbiosis and systemic inflammation, highlighting the potential role that probiotics may play in reducing intestinal permeability and oxidative stress and modulating neuroinflammatory processes (14).

In conclusion, while the effects of probiotics on schizophrenia and bipolar disorders still need further investigation, they show promise in the management of depression and potentially in ASD. Thanks to their ability to modulate the gut-brain axis by improving gut health and reducing inflammation, probiotics may present a novel adjuvant strategy for psychiatric disorders.

BIBLIOGRAPHY

1. Liu, L., & Zhu, G. (2018). Gut–Brain Axis and Mood Disorder. Frontiers in Psychiatry, 9. https://doi.org/10.3389/fpsyt.2018.00223.
2. Heym, N., Heasman, B., Hunter, K., , B., Wang, G., Siegert, R., Cleare, A., Gibson, G., , K., Sumich, A., & Sumich, A. (2019). The role of microbiota and inflammation in self-judgement and empathy: implications for understanding the brain-gut-microbiome axis in depression. Psychopharmacology, 236, 1459 – 1470. https://doi.org/10.1007/s00213-019-05230-2.
3. Margolis, K., Cryan, J., & Mayer, E. (2021). The Microbiota-Gut-Brain Axis: From Motility to Mood. Gastroenterology. https://doi.org/10.1053/j.gastro.2020.10.066.
4. Hou, Y., Li, J., & Ying, S. (2023). Tryptophan Metabolism and Gut Microbiota: A Novel Regulatory Axis Integrating the Microbiome, Immunity, and Cancer. Metabolites, 13(11), 1166. https://doi.org/10.3390/metabo13111166
5. Hamamah, S., Aghazarian, A., Nazaryan, A., Hajnal, A., & Covasa, M. (2022). Role of Microbiota-Gut-Brain axis in regulating dopaminergic signaling. Biomedicines, 10(2), 436. https://doi.org/10.3390/biomedicines10020436
6. Valles-Colomer, M., Falony, G., Darzi, Y., Tigchelaar, E. F., Wang, J., Tito, R. Y., Schiweck, C., Kurilshikov, A., Joossens, M., Wijmenga, C., Claes, S., Van Oudenhove, L., Zhernakova, A., Vieira-Silva, S., & Raes, J. (2019). The neuroactive potential of the human gut microbiota in quality of life and depression. Nature Microbiology, 4(4), 623–632. https://doi.org/10.1038/s41564-018-0337-x
7. Barbosa, I., Miranda, A., Berk, M., & Teixeira, A. (2024). The involvement of the microbiota-gut-brain axis in the pathophysiology of mood disorders and therapeutic implications. Expert review of neurotherapeutics. https://doi.org/10.1080/14737175.2024.2438646.
8. Mehta, I., Juneja, K., Nimmakayala, T., Bansal, L., Pulekar, S., Duggineni, D., Ghori, H. K., Modi, N., & Younas, S. (2025). Gut Microbiota and Mental Health: A Comprehensive Review of Gut-Brain Interactions in Mood Disorders. Cureus, 17(3), e81447. https://doi.org/10.7759/cureus.81447
9. Forssten, S., Ouwehand, A., Griffin, S., & Patterson, E. (2022). One Giant Leap from Mouse to Man: The Microbiota–Gut–Brain Axis in Mood Disorders and Translational Challenges Moving towards Human Clinical Trials. Nutrients, 14. https://doi.org/10.3390/nu14030568.
10. Liu, Q., He, H., Yang, J., Feng, X., Zhao, F., & Lyu, J. (2019). Changes in the global burden of depression from 1990 to 2017: Findings from the Global Burden of Disease study. Journal of Psychiatric Research, 126, 134–140. https://doi.org/10.1016/j.jpsychires.2019.08.002
11. Amirani, E., Milajerdi, A., Mirzaei, H., Jamilian, H., Mansournia, M., Hallajzadeh, J., & Ghaderi, A. (2020). The effects of probiotic supplementation on mental health, biomarkers of inflammation and oxidative stress in patients with psychiatric disorders: A systematic review and meta-analysis of randomized controlled trials. Complementary therapies in medicine, 49, 102361. https://doi.org/10.1016/j.ctim.2020.102361.
12. Skowrońska, M. (2023). The use of probiotics in the treatment of selected psychiatric disorders. Archives of Psychiatry and Psychotherapy, 3, 14-21.
13. Shaaban, S. Y., Gendy, Y. G. E., Mehanna, N. S., El-Senousy, W. M., El-Feki, H. S. A., Saad, K., & El-Asheer, O. M. (2017). The role of probiotics in children with autism spectrum disorder: A prospective, open-label study. Nutritional Neuroscience, 21(9), 676–681. https://doi.org/10.1080/1028415x.2017.1347746
14. Borkent, J., Ioannou, M., Neijzen, D., Haarman, B., & Sommer, I. (2024). Probiotic Formulation for Patients With Bipolar or Schizophrenia Spectrum Disorder: A Double-Blind, Randomized Placebo-Controlled Trial.. Schizophrenia bulletin. https://doi.org/10.1093/schbul/sbae188.