Single host-symbiont interactions should be reconsidered from the perspective of the pathobiome. We revisit here the interactions between entomopathogenic nematodes (EPNs) and their microbiota. We first describe the discovery of these EPNs and their bacterial endosymbionts. We also consider EPN-like nematodes and their putative symbionts. Recent high-throughput sequencing studies have shown that EPNs and EPN-like nematodes are also associated with other bacterial communities, referred to here as the second bacterial circle of EPNs. Current findings suggest that some members of this second bacterial circle contribute to the pathogenic success of nematodes. We suggest that the endosymbiont and the second bacterial circle delimit an EPN pathobiome. Rethinking host-microorganism interactions: from Koch's postulates to the notion of a 'pathobiome' Each era has its trends. In the biology of host-microorganism interactions, the 1990s focused on the basic mechanisms of these interactions, leading to a trend towards reductionism, the controllability of 'synthetic' systems and advances towards deciphering the molecular mechanisms of microbe infection processes [1]. For example, the molecular infection biology of Salmonella, a bacterium pathogenic to both humans and animals, has been described in detail over the past 40 years. The type 3 secretion system (T3SS) was identified as the key determinant of all pathogenic Salmonella strains, underlying their ability to invade nonphagocytic host cells [2]. Currently, microbiologists are revisiting the field of microbial ecology, with the aim of integrating various dimensions of complexity: genotypic, functional, and environmental [1]. Moreover, the conceptual framework of mechanistic studies based on Koch's postulates (see Glossary) is being challenged by several new concepts.