Comprehensive analysis of 84 Faecalibacterium prausnitzii strains uncovers their genetic diversity, functional characteristics, and potential risks

is a beneficial human gut microbe and a candidate for next-generation probiotics. With probiotics now being used in clinical treatments, concerns about their safety and side effects need to be considered. Therefore, it is essential to obtain a comprehensive understanding of the genetic diversity, functional characteristics, and potential risks of different strains. In this study, we collected the genetic information of 84 strains to conduct a pan-genome analysis with multiple perspectives. Based on single-copy genes and the sequences of 16S rRNA and the compositions of the pan-genome, different phylogenetic analyses of strains were performed, which showed the genetic diversity among them. Among the proteins of the pan-genome, we found that the accessory clusters made a greater contribution to the primary genetic functions of strains than the core and specific clusters. The functional annotations of showed that only a very small number of proteins were related to human diseases and there were no secondary metabolic gene clusters encoding harmful products. At the same time, complete fatty acid metabolism was detected in . In addition, we detected harmful elements, including antibiotic resistance genes, virulence factors, and pathogenic genes, and proposed the probiotic potential risk index (PPRI) and probiotic potential risk score (PPRS) to classify these 84 strains into low-, medium-, and high-risk groups. Finally, 15 strains were identified as low-risk strains and prioritized for clinical application. Undoubtedly, our results provide a comprehensive understanding and insight into , and PPRI and PPRS can be applied to evaluate the potential risks of probiotics in general and to guide the application of probiotics in clinical application.