Linking the effects of helminth infection, diet and the gut microbiota with human whole-blood signatures

Helminth infection and dietary intake can affect the intestinal microbiota, as well as the immune system. Here we analyzed the relationship between the fecal microbiota and blood profiles of indigenous Malaysians, called the Orang Asli, in comparison to urban control participants from the capital city of Malaysia, Kuala Lumpur. A nutritional questionnaire was used to identify dietary covariates that are associated with variations in microbial composition and whole blood transcriptomic profiles. We found that helminth infections had a larger effect on the gut microbiota than dietary parameters or blood profiles. Trichuris trichiura infection intensity also had the strongest association with blood transcriptional profiles of all factors investigated. By characterizing paired longitudinal samples collected before and after deworming treatment, we determined that changes in serum zinc and iron levels among the Orang Asli were driven by changes in helminth infections or associated factors such as microbial communities, independent of dietary metal intake. Serum zinc levels were positively associated with Clostridiales and Victivallales abundance, whereas serum iron levels were associated with Bacteroidales, Clostridiales and Erysipelotrichales abundance. Hence, there is considerable interplay between helminths, micronutrients and the microbiota on the regulation of immune responses in humans.