Microbiotas are complex microbial communities that colonize specific niches in the host and provide essential organismal functions that are important in health and disease. Understanding the ability of each distinct community member to promote or impair host health, alone or in the context of the community, is imperative for understanding how differences in community structure affect host health and vice versa. Recently, a reference 12-member microbiota for the model organism Caenorhabditis elegans, known as CeMbio, was defined. Here, we show the differential ability of each CeMbio bacterial species to activate innate immunity through the conserved PMK-1/p38 MAPK, ACh-WNT, and HLH-30/TFEB pathways. Although distinct CeMbio members differed in their ability to activate the PMK-1/p38 pathway, the ability to do so did not correlate with bacterial-induced lifespan reduction in wild-type or immunodeficient animals. In contrast, most species activated HLH-30/TFEB and showed virulence toward hlh-30-deficient animals. These results suggest that the microbiota of C. elegans is rife with bacteria that can shorten the host's lifespan if host defense is compromised and that HLH-30/TFEB is a fundamental and key host protective factor.