**5. Conclusions**

*C. elegans* represents a valuable in vivo model for studying how probiotics interact with the host and what mechanisms are involved in prolongevity. Its numerous tools and the possibility of genetic approaches has allowed advances in understanding these interactions. *C. elegans* shows highly conserved pathways through which the host responds to microbes, revealing cross-talk regulating longevity, ageing, stress resistance, and innate immune responses. The unique opportunity to manipulate its diet renders *C. elegans* a powerful model organism for understanding the effect of bacteria on these interconnected processes. Moreover, it also represents a low expensive screening tool to identify novel probiotic strains from a large number of microbial candidates. The picture emerging from this review evidences that several probiotic strains are able to exert anti-ageing effects in nematodes, by acting on common, conserved molecular pathways, such as IIS and p38 MAPK. The cell wall components of probiotic bacteria are thought to be primarily responsible for immunostimulation, as clearly demonstrated for TLRs-MAMPs interactions. Moreover, key ageing- and stress-associated regulatory elements, such as DAF-16/FOXO and HSF-1 transcription factors, also emerged as common targets of probiotic activities. However, other important mediators still need to be identified and characterized. In this perspective, *C. elegans* therefore appears to be advantageous to unravel key mechanisms involved in host prolongevity in response to probiotics supplementation. Since these mechanisms appear to be conserved across several species, the possibility of promoting the longevity of humans through the consumption of probiotics is gaining increasing attention. Indeed, probiotic supplementation has been suggested to slow or reverse the age-related changes in intestinal microbiota composition, as well as the gradual decline of immune function in elderly, thus lowering the risk of associated age-related morbidities. Nevertheless, future studies are needed to deepen insight on the effect of probiotics on longevity in mammals.

**Author Contributions:** Review structuring: D.U. and C.D.; Literature searching: C.D. and M.R.; Manuscript drafting: D.U., C.D., M.R., B.G., P.Z. and E.S.; Manuscript critical revision: D.U., C.D. and M.R.; Figures preparation: E.S.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The authors declare no conflicts of interest.
