Unlocking the Potential of Probiotics: A Comprehensive Review on Research, Production, and Regulation of Probiotics
Open accessAbstract
This review provides a comprehensive overview of the current state of probiotic research, covering a wide range of topics, including strain identification, functional characterization, preclinical and clinical evaluations, mechanisms of action, therapeutic applications, manufacturing considerations, and future directions. The screening process for potential probiotics involves phenotypic and genomic analysis to identify strains with health-promoting properties while excluding those with any factor that could be harmful to the host. In vitro assays for evaluating probiotic traits such as acid tolerance, bile metabolism, adhesion properties, and antimicrobial effects are described. The review highlights promising findings from in vivo studies on probiotic mitigation of inflammatory bowel diseases, chemotherapy-induced mucositis, dysbiosis, obesity, diabetes, and bone health, primarily through immunomodulation and modulation of the local microbiota in human and animal models. Clinical studies demonstrating beneficial modulation of metabolic diseases and human central nervous system function are also presented. Manufacturing processes significantly impact the growth, viability, and properties of probiotics, and the composition of the product matrix and supplementation with prebiotics or other strains can modify their effects. The lack of regulatory oversight raises concerns about the quality, safety, and labeling accuracy of commercial probiotics, particularly for vulnerable populations. Advancements in multi-omics approaches, especially probiogenomics, will provide a deeper understanding of the mechanisms behind probiotic functionality, allowing for personalized and targeted probiotic therapies. However, it is crucial to simultaneously focus on improving manufacturing practices, implementing quality control standards, and establishing regulatory oversight to ensure the safety and efficacy of probiotic products in the face of increasing therapeutic applications.
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Numerous investigations have examined the distribution of bsh genes across different species, correlating them with substrate-specific BSH activities.
“Consequently, BSH activity is widely recognized as a key criterion for probiotic selection, and numerous investigations have examined the distribution of bsh genes across different species, correlating them with substrate-specific BSH activities [70].”
From Bile Salt Hydrolase Activity in the Food-Derived Strain Levilactobacillus brevis M3R3: Genomic and Functional Characterization (2026) · cites this paper as [70]
The Bile Tolerance and Metabolism section (page not available) describes BSH enzymes across bacterial genera and reports differences in activity by strain and bile-acid substrate. It does not report investigations of bsh gene distribution or correlations between those genes and substrate-specific activity. (LLM, conf=0.85)
Experimental — accuracy not yet measuredBSH activity is widely recognized as a key criterion for probiotic selection.
“Consequently, BSH activity is widely recognized as a key criterion for probiotic selection, and numerous investigations have examined the distribution of bsh genes across different species, correlating them with substrate-specific BSH activities [70].”
From Bile Salt Hydrolase Activity in the Food-Derived Strain Levilactobacillus brevis M3R3: Genomic and Functional Characterization (2026) · cites this paper as [70]
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Vitellio, P., Celano, G., Bonfrate, L., Gobbetti, M., Portincasa, P., & Angelis, M. D. (2019) · Nutrients · doi:10.3390/nu11040886 · Cited by 145 · see citing works
Pathophysiology of Inflammatory Bowel Disease: An Overview
Thoreson, R., & Cullen, J. J. (2007) · Surgical Clinics of North America · doi:10.1016/j.suc.2007.03.001 · Cited by 143 · see citing works
Roshchina, V. V. (2016) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-20215-0_2 · Cited by 143 · see citing works
Gomes, A. C., de Sousa, R. G. M., Botelho, P. B., Gomes, T. L. N., Prada, P. O., & Mota, J. F. (2016) · Obesity · doi:10.1002/oby.21671 · Cited by 143 · see citing works
(BIOHAZ), E. P. O. B. H., Koutsoumanis, K., Allende, A., Alvarez‐Ordóñez, A., Bolton, D., Bover‐Cid, S., Chemaly, M., Davies, R., De Cesare, A., Hilbert, F., et al. (2022) · EFSA Journal · doi:10.2903/j.efsa.2022.7045 · Cited by 143 · see citing works
Sánchez, M., Darimont, C., Panahi, S., Drapeau, V., Marette, A., Taylor, V. H., Doré, J., & Tremblay, A. (2017) · Nutrients · doi:10.3390/nu9030284 · Cited by 138 · see citing works
Safety Evaluations of Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI
Kim, M. J., Ku, S., Kim, S. Y., Lee, H. H., Jin, H. Z., Kang, S., Li, R., Johnston, T. V., Park, M. S., & Ji, G. E. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051422 · Cited by 138 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Kang, M. H., Elnar, A. G., & Kim, G.-B. (2025) · Food Science of Animal Resources · doi:10.5851/kosfa.2025.e1 · Cited by 21 · see citing works
Agolino, G., Cristofolini, M., Vaccalluzzo, A., Tagliazucchi, D., Cattivelli, A., Pino, A., Caggia, C., Solieri, L., & Randazzo, C. L. (2025) · Biomolecules · doi:10.3390/biom15010086 · Cited by 19 · see citing works
Agolino, G., Cristofolini, M., Ronsivalle, M. A., Cattivelli, A., Tagliazucchi, D., Caggia, C., Solieri, L., & Randazzo, C. L. (2026) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-025-10810-0 · Cited by 1 · see citing works
- Authors
- da Silva, T. F., Glória, R. D. A., Americo, M. F., Freitas, A. D. S., de Jesus, L. C. L., Barroso, F. A. L., Laguna, J. G., Coelho-Rocha, N. D., Tavares, L. M., le Loir, Y., Jan, G., Guédon, É., & Azevedo, V. A. D. C.
- Affiliations
- Universidade Federal de Minas Gerais (BR)
- Institut Agro Rennes-Angers (FR)
- ORCID
- Venue
- Probiotics and Antimicrobial Proteins
- Published
- 2024-03-28
- Volume
- 16
- Issue
- 5
- Pages
- 1687-1723
- ISSN
- 1867-1306 (ISSN-L)
- 1867-1314
- OpenAlex
- W4393276045
- Cited by
- 117
- References
- 378
- Citations by year
- 2026: 58 · 2025: 45 · 2024: 14
- FWCI
- 4.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Probiotics and Antimicrobial Proteins (publishedVersion, other-oa)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Topics
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Nursing › Nutrition and Dietetics › Infant Nutrition and Health
- Keywords
- probiotics, acid resistance, bile tolerance, probiotic adhesion, antimicrobial activity, inflammatory bowel disease, chemotherapy-induced mucositis, dysbiosis, obesity, diabetes mellitus, bone health, immunomodulation, gut microbiota, probiotic quality control, probiotic regulation, prebiotics, probiogenomics, multi-omics
- MeSH terms
- Animals, Humans, Probiotics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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