Revisiting geophagy: An evolved sickness behavior to microbiome-mediated gastrointestinal inflammation

Geophagy, the consumption of clay or similar substances, is known as an evolved behavior that protects vulnerable populations, such as pregnant women and children, against gastrointestinal injury. However, perplexing questions remain, like the presence of geophagy in the absence of overt gastrointestinal infection and the potential causal relationship between geophagy and iron deficiency anemia. In this review, we hypothesize that geophagy is an inflammation-mediated sickness behavior regulated via the vagus nerve. We further hypothesize that the gut microbiome plays a critical role in mediating the relationship between inflammation and geophagy. By including inflammation and the microbiome within the existing protection hypothesis, we can explain how subclinical gastrointestinal states induce geophagy. Furthermore, we can explain how gastrointestinal inflammation is responsible for both geophagy and iron-deficiency anemia, explaining why the two phenomena frequently co-occur. Ultimately, defining geophagy as a sickness behavior allows us to integrate the gut-brain axis into geophagy research.