Fertility and germline stem cell maintenance under different diets requires nhr-114/HNF4 in C. elegans

Animals can thrive on variable food resources as a result of autonomous processes and beneficial relationships with their gut microbes [1]. Food intake elicits major physiological changes, which are counteracted by transient systemic responses that maintain homeostasis in the organism. This integration of external information occurs through cellular sensory elements, such as nuclear receptors, which modulate gene expression in response to specific cues [2]. Given the importance of germline stem cells (GSCs) for the development of the germline and the continuity of species, it is reasonable to assume that GSCs might be shielded from the negative influence of environmental perturbations. To our knowledge, however, there are no mechanisms reported that protect GSCs from harmful dietary metabolites. Using Caenorhabditis elegans as a model, we report that the somatic activity of the conserved nuclear receptor nhr-114/HNF4 protects GSC integrity from dietary metabolites. In the absence of nhr-114 and on certain bacterial diets, otherwise somatically normal animals accumulate germ cell division defects during development and become sterile. We found that, in nhr-114(-) animals, the induction of germline defects and sterility depend on bacterial metabolic status, with respect to the essential amino acid tryptophan. This illustrates an animal-microbe interaction in which somatic nuclear receptor activity preserves the germline by buffering against dietary metabolites, most likely through a somatic detoxifying response. Overall, our findings uncover an unprecedented, and presumably evolutionarily conserved, soma-to-germline axis of communication that maintains reproductive robustness on variable food resources.