Psychobiotics: A Revolutionary Shift In Treatment for Mental Health

Rachelle DiMedia

Have you ever experienced “butterflies” in your stomach before a big event? That’s your gut and brain communicating—and scientists are discovering this connection is more profound than they previously thought.

Depression and anxiety present a significant burden on society and those who suffer from them. They are a leading cause of disability in the U.S., affecting not only the individual but also their loved ones. There is a growing need to discover therapies that can conquer these ailments and alleviate their burden, without causing significant side effects.

Interest in alternative therapies has been growing rapidly. Although the first study evaluating the use of prebiotics and postbiotics for mental health was conducted over a decade ago, approximately half of all existing literature has been published in the last two years, demonstrating the rapid pace of ongoing research.⁵

Despite recent advances in understanding the microbiome-gut-brain axis, many questions still remain. Until we uncover the biological mechanisms of this system, its potential as a pharmacological target to enhance brain-gut health cannot be fully realized. Furthermore, the scientific community has yet to determine the proper uses for prebiotics and probiotics, whether as supplementary treatments alongside existing central nervous system (CNS) therapies or as a universal solution for all affected groups, including those untreated and at risk. Since each person’s microbiome is unique and research in this area is limited, selecting the optimal combination of microbes for CNS disorders remains a challenge.

While evidence indicates that psychobiotics would be clinically beneficial, diverse human study protocols have created challenges in translating these results into patient care. One challenge in collating information from these studies is the varying designs. A homogeneous approach to evaluating behavioral outcomes is necessary for both preclinical and clinical studies. Standardized tools must be created and used to measure aspects such as emotional regulation and mindfulness.

Early studies show promise. People taking psychobiotic supplements have reported less anxiety, better sleep, and even improved memory. But this research is still new, and psychobiotics aren’t a substitute for professional mental health care.

The microbiome is a complex community of bacteria, fungi, viruses, and other microorganisms that reside in the digestive tract.  Mechanical and electrical signals are exchanged between the brain and gut, regulating and maintaining not only our mood but also brain structure and function.

This bidirectional communication highway involves the enteric system, the hypothalamus-pituitary-adrenal axis (HPA), and a vast network of neurons primarily located in the brain and the vagus nerve (for more information on the GBA, please see my recent article). Research shows that gut bacteria can influence mood, stress response, and even mental disorders like anxiety, depression, and bipolar disorder.¹ 

How do microbes influence brain function and behavior?

So, how do they work? Your gut produces about 90% of the body’s serotonin, a chemical that affects mood, sleep, and digestion. When your gut microbiome is healthy, it sends positive signals to the brain. When your microbiome is unhealthy, it sends negative signals, and areas in your brain responsible for aggression, anger, irritability, and antisocial behavior are activated. Additionally, gut microbes can create chemicals that can affect cognition, memory, and decision-making.²

https://neurosciencenews.com/psychobiotics-neuroscience-5353/

1.     Gut microbiota manufacture and degrade a wide array of metabolites and neuroactive compounds like neurotransmitters:

·      Serotonin

·      GABA

·      Cortisol

·      Short-chain fatty acids (SCFAs)

2.     The immune system is intricately linked to the GBA. It is modulated by microbiome-induced systemic inflammation, and proinflammatory cytokines will affect brain function and behavior.

3.   Neural pathways, primarily via the vagus nerve and spinal pathways, establish bidirectional communication between the microbiome and the brain. When neural circuitry is compromised by a negative alteration in the microbiome, it alters brain areas responsible for emotional regulation and decision-making.

4.     Microbiota are responsible for lipid metabolism, which produces and absorbs nutrients:

·      Vitamins

·      Omega-3 fatty acids

·      Polyphenols and their bioactive metabolites

The implications of recent advances in the microbiome extend beyond biology and may even have significant legal ramifications. There is a rare condition called auto-brewery syndrome. An overgrowth of harmful bacteria in the gut ferments dietary carbohydrates and sugar into ethanol, which the body absorbs, producing blood alcohol levels sufficient to cause the symptoms of intoxication without consuming alcohol. The condition is often linked to antibiotic use, poor nutrition, and pre-existing health issues. In fact, there have been cases where drunk driving charges were dismissed, including one in New York in 2019. The involved individuals showed that consuming a large amount of carbohydrates caused their bodies to produce alcohol, which impaired their behavior and indicated that their actions were not due to alcohol consumption. 

What are Psychobiotics?

To answer this, we must first explain the concepts of prebiotics and probiotics, as well as their differences.  

·      Prebiotics are organic compounds found in certain foods, supplements, and the gut. They function as a food source for your gut’s microorganisms, allowing them to live and grow.  Multiple byproducts are produced by the metabolism of these healthy microorganisms, resulting in a variety of beneficial effects on both the body and mind.

·      Probiotics are live microorganisms that reside in your gut and have beneficial effects when consumed in adequate amounts and in a variety of forms.  They can be found in certain foods and supplements.

·      Psychobiotics, a subgroup of probiotics, are live organisms that may enhance mental health by supporting the gut-brain connection. These beneficial microbes are present in certain probiotics and fermented foods. Emerging strategies are being developed to introduce brain-boosting bacteria into the gut, aiming to provide mental benefits, while also addressing the challenges ahead in understanding how these products may work in humans.

Psychobiotics have the potential to replace the low-dose antianxiety and antidepressant medications that have become ubiquitous in society today. These powerful strains of beneficial bacteria could someday serve as an alternative for achieving optimal mental health without the side effects and withdrawal issues associated with other pharmaceuticals. However, their full potential has yet to be realized. Psychobiotics may help reduce inflammation, regulate stress hormones, and influence neurotransmitter activity—all of which play a role in mood disorders like anxiety and depression.¹

Ongoing research continues to improve our understanding of host-microbiome interactions, enabling the identification of the most effective psychobiotic strains capable of optimizing the gut-brain axis function and, ultimately, mental health.¹  

What microbial strains are most beneficial?

It has become apparent that mental health is deeply intertwined with physiological processes extending beyond the brain itself.   Factors affecting the GBA fluctuate and are both internal and external. If we can discover how to modulate this system through the use of psychobiotics, we could unlock the key to overcoming or at least improving multiple mental health issues that plague society today, but which strains work best?¹

Bifidobacterium longum: Multiple trials conducted over the last decade have found that using this strain of psychobiotic, over time, can reduce stress, depression, and anxiety. Evidence also showed that participants displayed improved memory, reduced cortisol output in response to stress, and direct effects on brain function related to emotional states. Additionally, improved sleep quality was linked to better daytime functioning, reduced sleepiness, and increased energy and vitality in otherwise healthy individuals with impaired sleep. Longum has also demonstrated anti-obesity effects.

Lacticaseibacillus rhamnosus: This bacterial strain has been beneficial for women suffering from postpartum depression and anxiety when it is given to them in the 2^nd trimester and until 6 months postpartum.

The combination of Lactobacillus helveticus and B. longum has been investigated for over a decade, with mixed results. The use of these two strains over 30 days, in conjunction with positive healthy behaviors (diet, physical activity, sleep quality, nature exposure, contact, social media use, and substance abuse) was the single best predictor of reduced anxiety, improved emotional regulation, and mindfulness. Emotional regulation results were measured using self-reporting and records of altered behavior.

Microbial metabolites, specifically short-chain fatty acids (SCFAs), were delivered via the colon.  They demonstrated anxiolytic effects by exhibiting a blunted cortisol response to stress exposure.

Looking forward

Recent studies have found that potential microbiome modulation could improve human welfare, reduce suffering, and dramatically decrease society’s mental health crisis. It may have far-reaching implications beyond science, potentially affecting long-held legal decisions and forensic psychiatry. If we can also better understand the environmental factors that affect our microbiome, from diet to socioeconomic inequities, we may have the opportunity to create rehabilitative and preventive measures through this modality.  The results of ongoing research could significantly improve humanity if the knowledge is disseminated worldwide and utilized to address some of the most pressing issues in society today.²

REFERENCES:

1.     Slykerman RF, Davies N, Vlckova K, O'Riordan KJ, Bassett SA, Dekker J, Schellekens H, Hyland NP, Clarke G, Patterson E. Precision Psychobiotics for Gut-Brain Axis Health: Advancing the Discovery Pipelines to Deliver Mechanistic Pathways and Proven Health Efficacy. Microb Biotechnol. 2025 Jan;18(1):e70079. doi: 10.1111/1751-7915.70079. PMID: 39815671; PMCID: PMC11735468.

2.     Logan AC, Mishra P, Prescott SL. The Legalome: Microbiology, Omics and Criminal Justice. Microb Biotechnol. 2025 Mar;18(3):e70129. doi: 10.1111/1751-7915.70129. PMID: 40072296; PMCID: PMC11898878.

3.     Tognini P. Psychobiotics: Feeding the gut to nurture the brain. Nat Rev Neurosci. 2023;24(3):131-144. doi:10.1038/s41583-023-00670-5

4.     Sarkar A, Lehto SM, Harty S, Dinan TG, Cryan JF. Psychobiotics and the manipulation of bacteria–gut–brain signals. Trends Neurosci. 2022;45(11):861-876. doi:10.1016/j.tins.2022.08.001

5.     Liu RT, Walsh RFL, Sheehan AE. Prebiotics and probiotics for depression and anxiety: A systematic review and meta-analysis of controlled clinical trials. Neurosci Biobehav Rev. 2019 Jul;102:13-23. doi: 10.1016/j.neubiorev.2019.03.023. Epub 2019 Apr 17. PMID: 31004628; PMCID: PMC6584030.