Indeed, the role of TLRs as mediators of the microbiome–gut brain axis and innate immune system in PD has been elegantly reviewed previously [4], whereas this piece focuses on the role of TLR2 and TLR4 in gut physiology overall and a possible contribution to early PD pathogenesis through a local effect on gut and ENS function. This evidence concerns the gene TLR2 and Parkinson disease.