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The Promise of Psychobiotics

The effective psychobiotic: These three considerations will help pave the way.

Key points

  • Not all probiotics are psychobiotics.
  • Psychobiotic formulation should begin by matching strain mechanisms with symptoms.
  • An effective psychobiotic will demonstrate specific clinical outcomes, gastric survival, and full shelf-life activity.

By Nicole Cain, ND, MA

Psychobiotics are probiotics that confer mental health benefits to the host when ingested in a particular quantity through interaction with commensal gut bacteria.1 Although psychobiotics operate through a variety of mechanisms, it is believed that the gut-brain benefits primarily result through influence on the hypothalamic-pituitary-adrenal (HPA) axis, healthy immune and inflammation support, and production of neurohormones and neurotransmitters.2

With so many different types of probiotics to choose from, many claiming mental health benefits, selecting the best formulation can be challenging. Here is a reliable method for choosing well.

In the Beginning

Anna Bocharova/Dreamstime
Heal the Gut
Source: Anna Bocharova/Dreamstime

Early probiotic formulations contained probiotic strains that cast a wide net, offering general microbiome support. These commonly included Bifidobacterium, Lactobacillus, and the yeast Saccharomyces boulardii without specific attention to individual strain strengths and the degree of synergies between them. However, research has confirmed that different probiotic strains perform different functions in the management of health and specific disease.3 And as personalized and precision medicine has gained popularity, developers of probiotic formulations have expanded beyond the one-size-fits-all approach to developing precision-based probiotic formulations. But not all formulations are backed by quality processes and positive outcomes. Consideration of the following three characteristics will help identify an optimal brand while avoiding thoughtless formulation and baseless claims.

1. Informed Strain Selection

When selecting the appropriate strains for specific health conditions, the first step is to identify what symptoms are in need of support. In a review published in the journal Nutrients, authors emphasized this concept, stating: “It is important to select probiotics strains that can influence the disturbed physiological processes in the health condition that is targeted by the respective probiotic product.”4

For example, many mental health symptoms including depression, anxiety, and rumination are exacerbated by system-wide inflammation. This is caused by damage to intestinal cells resulting in microbes and toxins entering the bloodstream (leaky gut). In such a case, the best results are likely to come from a probiotic that contains anti-inflammatory strains capable of repairing intestinal wall tight junctions. Quality manufacturers will test strains for this ability and often publish the results. For example, strains including Lactobacillus casei W56, Lactococcus lactis W19, Lactobacillus acidophilus W22, and Bifidobacterium lactis W52, are directly associated with improved gut barrier function and the reduction of related mood disorders.5

Valeria Gaipova/Dreamstime/
Source: Valeria Gaipova/Dreamstime/

Listen to My Psychobiotic Case Study

On the other hand, symptoms of insomnia may be better supported with probiotics containing bacteria that produce the relaxing neurotransmitter GABA, such as select strains from the Bifidobacteria family.6 Finding the right psychobiotic therefore starts with matching strains to symptoms and then having confidence that the combined strains operate synergistically.

2. Demonstrated Strain Synergies

While single probiotic strains have been shown to be beneficial to health, multi-strain probiotics have the potential to be significantly more effective due to synergies and additive effects.7 But it is important to realize that not all strains collaborate. In fact, some are antagonistic. When planning a final psychobiotic formulation, collaboration needs to be considered. The most reliable method of assuring strain synergies toward a positive health outcome is through human clinical trials. Although expensive, a high-quality manufacturer will invest in this type of evidence using the exact commercial formulation available to consumers. And many of these studies are readily available for review online.

3. Quality Manufacturing Processes

By definition, all probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host.8 The live part is foundational, but also one of the most challenging hurdles in guaranteeing “bench-to-market” probiotic activity.

a. Formulation Matrix

Small changes in probiotic production can have large effects on the quality and performance of the product. For example, the manufacturing environment and product matrix (medium composition), namely factors including the amount of carbon, nitrogen, macro and micronutrients, prebiotic fibers, and pH, all have to be carefully calculated.3 Although allergen avoidance is generally a best practice, ingredients in the supporting matrix should play a direct role in the health and viability of the probiotics themselves. A quality manufacturer will be able to defend the use of every ingredient in a formulation. And the cleanest approach will avoid undesirable additives.

b. Probiotic Viability

As live microorganisms, it is of the utmost importance to ensure probiotic organisms are still viable by the time they are purchased and consumed–as measured in colony-forming units (CFU).

Exposure to oxygen is a significant consideration in determining viability over time. Depending on storage and packaging, CFU at the time of manufacturing can vary significantly throughout the shelf life. Some manufacturers use special capsules for protection while others have solved this problem by individual dose packaging (sachets). In either case, a quality manufacturer will have the data to demonstrate both gastric tolerance and real-time stability through the expiration date. Gastric tolerance refers to the probiotics’ ability to tolerate the stomach’s extremely low pH, digestive enzymes, bile salts, etc. This testing can involve using an artificial gut system that mimics human digestion. Real-time stability testing will also demonstrate that the CFU stated on the package is the CFU that is delivered right up until the date of expiration. A quality manufacturer will have this information readily available.

Closing Remarks

Targeted interventions in the form of psychobiotics offer a complementary mental health solution that is effective, safe to use alongside conventional therapies, and can be fast-acting, especially when supported with a whole food diet rich in prebiotic fibers. In fact, according to a 2019 publication in Nutrients, “manipulation of macronutrient intake can consistently shift the composition of the gut microbiota within the span of a day.9

A daily psychobiotic can be a great addition to bolster the gut-brain axis and mental well-being. But not all formulations are the same. Doing the diligence to ensure quality and efficacy will make all the difference.



2. Del 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;12(12):3896. Published 2020 Dec 19. doi:10.3390/nu12123896

3. Visconti A, Le Roy CI, Rosa F, Rossi N, Martin TC, Mohney RP, Li W, de Rinaldis E, Bell JT, Venter JC, Nelson KE, Spector TD, Falchi M. Interplay between the human gut microbiome and host metabolism. Nat Commun. 2019 Oct 3;10(1):4505. doi: 10.1038/s41467-019-12476-z. PMID: 31582752; PMCID: PMC6776654.

4. Grumet L, Tromp Y, Stiegelbauer V. The Development of High-Quality Multispecies Probiotic Formulations: From Bench to Market. Nutrients. 2020;12(8):2453. Published 2020 Aug 15. doi:10.3390/nu12082453

5. Moser AM, Spindelboeck W, Halwachs B, Strohmaier H, Kump P, Gorkiewicz G, Högenauer C. Effects of an oral synbiotic on the gastrointestinal immune system and microbiota in patients with diarrhea-predominant irritable bowel syndrome. Eur J Nutr. 2019 Oct;58(7):2767-2778. doi: 10.1007/s00394-018-1826-7. Epub 2018 Sep 24. PMID: 30251020; PMCID: PMC6768888.

6. Science 2021.…

7. Kwoji ID, Aiyegoro OA, Okpeku M, Adeleke MA. Multi-Strain Probiotics: Synergy among Isolates Enhances Biological Activities. Biology (Basel). 2021;10(4):322. Published 2021 Apr 13. doi:10.3390/biology10040322


9. Leeming ER, Johnson AJ, Spector TD, Le Roy CI. Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration. Nutrients. 2019;11(12):2862. Published 2019 Nov 22. doi:10.3390/nu11122862

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