Emerging pre-clinical safety assessments for potential probiotic strains: a review

Abstract

Probiotics are amply studied and applied dietary supplements of greater consumer acceptance. Nevertheless, the emerging evidence on probiotics-mediated potential risks, especially among immunocompromised individuals, necessitates careful and in-depth safety studies. The traditional probiotic safety evaluation methods investigate targeted phenotypic traits, such as virulence factors and antibiotic resistance. However, the rapid innovation in omics technologies has offered an impactful means to ultimately sequence and unknot safety-related genes or their gene products at preliminary levels. Further validating the genome features using an array of phenotypic tests would provide an absolute realization of gene expression dynamics. For safety studies in animal models, the in vivo toxicity evaluation guidelines of chemicals proposed by the Organization for Economic Co-operation and Development (OECD) have been meticulously adopted in probiotic research. Future research should also focus on coupling genome-scale safety analysis and establishing a link to its transcriptome, proteome, or metabolome for a fine selection of safe probiotic strains. Considering the studies published over the years, it can be inferred that the safety of probiotics is strain-host-dose-specific. Taken together, an amalgamation of in silico, in vitro, and in vivo approaches are necessary for a fine scale selection of risk-free probiotic strain for use in human applications.

Keywords:

• Cytotoxicity
• genotoxicity
• omics
• oral toxicity
• preclinical safety
• probiotics

Acknowledgements

The authors are thankful to the Director, ICAR-NDRI, Karnal, Haryana India. PVB is grateful to National Centre for Veterinary Type Cultures (NCVTC), Hisar, Haryana, India for providing financial assistance. HY is supported by funding from the National Institutes of Health, the US Department of Defense, Florida Department of Health, and thankful for the support from the USF Center for Microbiome Research, Microbiomes Institute, University of South Florida.

Author contributions

Basavaprabhu Haranahalli Nataraj: Conceptualization; Data curation; Project administration; Investigation; Writing – original draft. Pradip V. Behare: Conceptualization; Funding acquisition; Data curation; Supervision; Writing – review & editing. Hariom Yadav: Conceptualization; Data curation; Writing – review & editing. A. K. Srivastava: Conceptualization; Project administration; Supervision; Writing – review & editing.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.