The gut microbiome in early life predicts malaria susceptibility.

Background: Despite intensive international efforts and broad implementation of control and prevention efforts, malaria continues to take a devastating toll on the most vulnerable populations, especially infants and young children. Emerging data support an important role for gut microbiome disruption in exacerbating, and potentially contributing to, adverse outcomes in malaria in young children. Less well understood are the role of the gut microbiome in early infancy in determining malaria susceptibility and how malaria exposure may impact gut microbial communities during this highly dynamic and sensitive period of microbiome development. Methods: To address these gaps, we recruited mother-infant dyads at birth in malaria-endemic eastern Democratic Republic of Congo. Infant fecal samples collected at six weeks, and at three, six and 12 months of age, as well as at passive malaria sick and post-treatment visits, were subjected to full length 16S rRNA sequencing. Results: Significant differences in relative abundance of a number of bacterial species distinguished those infants who never had a malaria visit from those who did, and those malaria episodes resulted in gut dysbiosis. Classifier analysis with Boruta selection revealed preliminary predictive capacity of the six-week fecal microbiome for malaria susceptibility through the first year of life, with a modest signal partially intertwined with bednet use. Healthy gut-associated Conclusions: These results provide the first evidence that gut microbial composition in early infancy is associated with subsequent malaria susceptibility. These associations, if confirmed in larger cohorts, may inform future investigation of microbiome-targeted strategies to support resistance to malaria in early life.