Addressing safety concerns of long-term probiotic use: In vivo evidence from a rat model

The global market for probiotic supplements is continually expanding. However, the certainty of their safety is still a matter of concern. Since multi-strain probiotics are gaining increasing interest in clinical practice, the aim of the presented study was to evaluate the long-term effects of probiotic mixture on healthy Wistar rats with the focus on colon histology, haematology, serum biochemistry, inflammatory cytokine production and faecal microbiota composition. The long-term supplementation resulted in systemic pro-inflammatory response accompanied by increased abundance of bacterial families associated with the promotion of gastrointestinal inflammation. The important indicators of cardiovascular risk were significantly elevated after long-term probiotic treatment. Even though no histopathological lesions were detected in the colon, enlarged lymphoid aggregates and follicles were observed in probiotic-fed rats. Based on our study, commercially available probiotics for human use which are recommended as prophylaxis should be monitored for possible side effect after longterm usage. Our study thus contributes to the increasingly debated proposal of the scientific community which suggests the need to shift the future of probiotic prescription from the current 'one-size-fits-all' scheme into a person/condition-tailored approach with defined time of administration.

Automated summary

This study evaluated the long-term effects of probiotic mixture on healthy Wistar rats, focusing on colon histology, haematology, serum biochemistry, inflammatory cytokine production, and faecal microbiota composition. Long-term supplementation of probiotics led to a systemic pro-inflammatory response and an increase in bacterial families associated with gastrointestinal inflammation. Important indicators of cardiovascular risk were elevated after long-term probiotic treatment. Although no histopathological lesions were found in the colon, enlarged lymphoid aggregates and follicles were observed. This study supports the suggestion to tailor probiotic prescription based on individual conditions and define the time of administration.