How to Optimize Your Microbiome With Simple, Synergistic Probiotic Strains

The gut is a complex ecosystem inhabited by trillions of microorganisms, collectively known as the gut microbiota. 

These microorganisms play a crucial role in various bodily functions, including digestion, immune regulation, and mental health. A balanced and diverse gut microbiota is essential for overall well-being.

Probiotics and Gut Health Benefits

"Probiotics" have garnered widespread attention for their numerous health benefits, especially when maintaining a healthy gut. These are live non-pathogenic microorganisms, including lactic acid bacteria, such as Lactobacillus and Bifidobacterium species, which naturally inhabit the human colon (commensal bacteria). 

Probiotics may also comprise non-commensal strains such as Bacillis subtilis and even Saccharomyces boulardii yeast that we can obtain from fermented foods, soil, fresh produce, and regulated dietary supplements. When consumed in adequate amounts, they provide a range of health benefits to the host. They introduce beneficial bacteria to the gut, helping maintain microbial balance and promote a healthy gut environment.

Why Less Is More When It Comes to Probiotics

As interest in probiotics grows, so does the variety of available products, each touting the most strains and the best results, subsequently confusing consumers. 

Products that combine many commensal strains in very high doses offer short-term or no benefits at all for three critical reasons: 

1. A lack of synergy or even competition of strains leads to low potency: While many strains exist in the human colon and theoretically are synergistic, they do not operate synergistically in a capsule - a vastly different environment than the human gut. Manufacturers try to offset this uncertainty by adding very high doses (overages) to anticipate the die-off, hoping some bacteria make it to the colon. 
2. Inability to properly colonize the colon: Strains in the probiotic supplement may not be able to withstand the harsh and variable environments that exist along the human gastrointestinal tract. From highly acidic stomach to the alkaline small intestine and eventually to the large intestine, where they colonize and live. While fermented foods with probiotic capabilities are effective, many supplemental formulations lack the clinical data to confidently conclude that proper colonization is occurring. 
3. Reduced tolerance due to adverse effects: Many probiotic supplements contain prebiotics that are used as fuel which can result in gas, bloating and uncomfortable reactions. Even formulations without these prebiotics can result in a short-term band-aid solution by providing microbial diversity only while continuing to take the probiotics and fewer long-term benefits after stopping. 

The Synergy Concept in Probiotics

Synergy refers to the cooperative action of different elements working together to produce a result that is greater than the sum of their individual effects. 

In the context of probiotics, this means that the selected strains complement each other, enhancing their overall effectiveness. An excellent example of synergy amongst probiotics is the combination of E. faecium T-110, C. butyricum TO-A, and B. subtilis TO-A. B harnessing the power of synergy through a carefully selected combination of fewer strains.

Advantages of Fewer Strains with Synergy:

1. Enhanced Stability: Having fewer strains in a probiotic formulation can lead to increased stability and viability of the product. Each strain requires specific environmental conditions to survive and thrive. With fewer strains, it is easier to ensure that these conditions are met, resulting in a more robust and reliable probiotic product.
2. Reduced Competition When it Matters: In probiotics with numerous competing strains, some strains may outcompete others, leading to less diverse and less effective gut microbiota. In contrast, carefully selected strains should demonstrate growth when in the same media rather than one or more strains degrading. This means that each strain works together harmoniously, reducing competition when in the capsule, in turn, leads to a balanced and diverse gut environment that outcompetes bad bacteria in the gut. For example, E. faecium T-110 naturally lives in the human gut. It produces lactic acid, which lowers the pH, preventing the growth of harmful bacteria while still being synergistic with Bifidobacterium species.
3. Targeted Benefits: By choosing specific strains that complement each other’s functions, we can address specific health concerns more effectively. For example, certain strains may focus on improving digestion, while others boost immune function. The synergy between the strains amplifies the overall impact on gut health. For example, C. butyricum TO-A also natural lives in the human gut and breaks down dietary fibre into several beneficial nutrients, one of which is butyric acid, which feeds cells of the GI tract.
4. Improved Colonization: The ability of probiotic strains to colonize the gut is crucial for their effectiveness. Selected strains should be able to withstand the harsh ecology along the human gastrointestinal tract. Those that are acid-resistant, spore-forming or inactivated may be more likely to first reach and then establish themselves and finally persist in the large intestine.
5. Minimized Side Effects: Some individuals may experience digestive discomfort when consuming probiotics with multiple competing strains. This is the result of high metabolic activity resulting in byproducts of fermentation irritating the colon or increasing gas production. Strains can use the by-products of another bacterial strain’s metabolism will thrive- like a chain reaction of growth. An example of this synergy is seen in the strain B. subtilis TO-A , which supports the growth of E. faecium and C. butyricum, as well as the growth of several strains of the beneficial Bifidobacterium species.

Clinical Relevance

As mentioned, many probiotic combinations use theory rather than clinical validation to support formulas. Taking a kitchen sink approach, throwing many strains with little data to support combinations into a capsule and hoping it makes it to and then colonizes the human gut. Rigorous testing of the interaction between strains in the capsule and in the gut is required to feel confident when taking a probiotic.

References:

1. Yoshimatsu Y, Yamada A, Furukawa R, Sono K, Osamura A, Nakamura K, Aoki H, Tsuda Y, Hosoe N, Takada N, Suzuki Y. (2015). Effectiveness of probiotic therapy for the prevention of relapse in patients with inactive ulcerative colitis. World J Gastroenterol. May 21;21(19):5985-94. doi: 10.3748/wjg.v21.i19.5985. 
2. Chen CC, Kong MS, Lai MW, Chao HC, Chang KW, Chen SY, Huang YC, Chiu CH, Li WC, Lin PY, Chen CJ, Li TY. (2010). Probiotics have clinical, microbiologic, and immunologic efficacy in acute infectious diarrhea. Pediatr Infect Dis J.Feb;29(2):135-8. doi: 10.1097/inf.0b013e3181b530bf.
3. Hua, M. C., Lin, T. Y., Lai, M. W., Kong, M. S., Chang, H. J., & Chen, C. C. (2010). Probiotic Bio-Three induces Th1 and anti-inflammatory effects in PBMC and dendritic cells. World journal of gastroenterology, 16(28), 3529–3540. https://doi.org/10.3748/wjg.v16.i28.3529
4. Ariyoshi, T., Hagihara, M., Takahashi, M., & Mikamo, H. (2022). Effect of Clostridium butyricum on Gastrointestinal Infections. Biomedicines, 10(2), 483. http://dx.doi.org/10.3390/biomedicines10020483
5. Fagnant, H.S., Isidean, S.D., Wilson, L., Bukhari, A.S., Allen, J.T., Agans, R.T., Lee, D.M., Hatch-McChesney, A., Whitney, C.C., Sullo, E., Porter, C.K., Karl, J.P.. (2023). Orally Ingested Probiotic, Prebiotic, and Synbiotic Interventions as Countermeasures for Gastrointestinal Tract Infections in Nonelderly Adults: A Systematic Review and Meta-Analysis. Advances in Nutrition. https://doi.org/10.1016/j.advnut.2023.02.002.
6. Kanai, T., Mikami, Y. & Hayashi, A. (2015). A breakthrough in probiotics: Clostridium butyricum regulates gut homeostasis and anti-inflammatory response in inflammatory bowel disease. J Gastroenterol 50, 928–939. https://doi.org/10.1007/s00535-015-1084-x