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Background  Skin-penetrating nematodes of the genus  Strongyloides  infect over 600 million people, posing a major global health burden. Their life cycle includes both a parasitic and free-living generation. During the parasitic generation, infective third-stage larvae (iL3s) actively engage in host seeking. During the free-living generation, the nematodes develop and reproduce on host feces. At different points during their life cycle,  Strongyloides  species encounter a wide variety of host-associated and environmental bacteria. However, the microbiome associated with  Strongyloides  species, and the behavioral and physiological interactions between  Strongyloides  species and bacteria, remain unclear.    Results  We first investigated the microbiome of the human parasite  Strongyloides stercoralis  using 16S-based amplicon sequencing. We found that  S. stercoralis  free-living adults have an associated microbiome consisting of specific fecal bacteria. We then investigated the behavioral responses of  S. stercoralis  and the closely related rat parasite  Strongyloides ratti  to an ecologically diverse panel of bacteria. We found that  S. stercoralis  and  S. ratti  showed similar responses to bacteria. The responses of both nematodes to bacteria varied dramatically across life stages: free-living adults were strongly attracted to most of the bacteria tested, while iL3s were attracted specifically to a narrow range of environmental bacteria. The behavioral responses to bacteria were dynamic, consisting of distinct short- and long-term behaviors. Finally, a comparison of the growth and reproduction of  S. stercoralis  free-living adults on different bacteria revealed that the bacterium  Proteus mirabilis  inhibits  S. stercoralis  egg hatching, and thereby greatly decreases parasite viability.    Conclusions  Skin-penetrating nematodes encounter bacteria from various ecological niches throughout their life cycle. Our results demonstrate that bacteria function as key chemosensory cues for directing parasite movement in a life-stage-specific manner. Some bacterial genera may form essential associations with the nematodes, while others are detrimental and serve as a potential source of novel nematicides.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12915-021-01153-7.

Skin-penetrating nematodes exhibit life-stage-specific interactions with host-associated and environmental bacteria