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Probiotics are commonly employed to address suboptimal or dysbiotic microbial populations. The microbiome is strongly implicated in host health, in part through the fermentation of non-digestible dietary carbohydrates to produce short-chain fatty acids. These compounds exert immunomodulatory and metabolic effects, serve as the primary nutrient substrate for intestinal colonocytes, act to acidify the intestinal medium to prevent pathogen growth, behave as signaling molecules in the gut-brain axis, and generally support robust gastrointestinal function.

The microbiome also participates in the synthesis and metabolism of bile acids, key components in the digestion of fats. Bile acids emulsify fats and fat-soluble vitamins for absorption, and, like short-chain fatty acids, demonstrate immunomodulatory, antimicrobial, and signaling roles. Microbial bile salt hydrolases catalyze bile acid deconjugation required for bile acid excretion. This process additionally amplifies bile acid antimicrobial activity, enhancing pathogen defense.

Each strain of bacteria contained within a probiotic exerts a specific effect on the microbiome. Understanding the impact of each strain and their interactions when combined is key for achieving a particular goal of microbiome modulation. A recent study set out to investigate the differential outcomes of three distinct probiotic formulations following a dosing protocol of 2 capsules/d totaling 2.7 x 10^11 CFU/day for 84 days.

The probiotic formulations were as follows:

• Probiotic 1 (P1): Lactobacillus acidophilus CUL60, L. acidophilus CUL21, Bifidobacterium bifidum CUL20, B. animalis subsp. lactis CUL34

• Probiotic 2 (P2): L. acidophilus CUL60, L. acidophilus CUL21, B. bifidum CUL20, B. animalis subsp. lactis CUL34, L. salivarius CUL61, L. paracasei CUL08, L. plantarum CUL66, L. casei CUL06, L. fermentum CUL67, L. gasseri CUL09, Pediococcus pentosaceus CUL15, B. breve CUL74, S. thermophilus CUL68, L. rhamnosus CUL63, L. reuteri JBD301, B. bifidum CUL73, L. helveticus CUL76

• Probiotic 3 (P3): L. rhamnosus GG, L. rhamnosus HN001, B. animalis ssp. lactis HN019

• Placebo: none

To comprehend the outcomes assessed, it is important to first define key terms:

• Richness — total number of distinct bacterial species within a sample.

• Diversity — a-diversity describes species variety and relative abundance within a sample; b-diversity describes the difference between microbial communities across distinct samples.

• Evenness — describes how evenly distributed species are within a sample.

• Shannon’s a-diversity — combines richness and evenness; highly sensitive to rare or low-abundance species, so the presence of a large quantity of rare species translates into a higher Shannon’s a-diversity. A higher value corresponds with greater species diversity and complexity.

• Simpson a-diversity index — emphasis on evenness; assesses probability that two individual microbes belong to the same species. A higher value indicates an even population and high diversity; a lower value suggests that a few species dominate.

At the conclusion of the study, neither Shannon’s a-diversity nor Simpson a-diversity index changed from baseline to endpoint in any intervention. B-diversity, however, was significantly increased in only the P1 group compared to all other interventions. Specifically, each probiotic combination affected specific bacterial strains as follows:

• P1 — significant increase in abundance of Agathobacter and Faecalibacterium with a concomitant decrease in Bifidobacterium

• P2 — significant increase in Faecalibacterium

• P3 — no change

All three probiotic groups additionally induced a shift in keystone profile. While fecal short-chain fatty acid levels were unaltered from baseline to endpoint regardless of the intervention, serum propionate significantly increased in both the P2 and P3 conditions. Serum butyrate also rose with P1 and P3. The bile acids lithocholic acid sulfate and chenodeoxycholic acid sulfate increased with P1 supplementation, a consistent observation following ingestion of the strain Lactobacillus gasseri LA39.

In summary, P1 induced changes in keystone strains, serum short-chain fatty acid profile, and fecal bile acids. P2 and P3, on the other hand, only impacted keystone strains and certain serum short-chain fatty acids. All three probiotics tended to promote proliferation of carbohydrate-metabolizing bacteria as well as producers of microbial bile salt hydrolases.

It is curious to note that diversity did not vary in the P2 condition despite the probiotic containing the same strains as the P1 supplement in addition to 13 others. It is possible that several strains compete or otherwise dilute one another’s potential. This study highlights the importance of properly selecting strains to achieve the desired health effect.

Michael DR, John DA, Coates N, et al. The impact of three distinct probiotic supplements on the gut microbiota and its metabolites in healthy adults. Benef Microbes. 2025;17(3):221-234. Published 2025 Sep 5. doi:10.1163/18762891-bja00096

Cassol I, Ibañez M, Bustamante JP. Key features and guidelines for the application of microbial alpha diversity metrics. Sci Rep. 2025;15(1):622. Published 2025 Jan 3. doi:10.1038/s41598-024-77864-y