Longitudinal analysis of infant stool bacteria communities before and after acute febrile malaria and artemether/lumefantrine treatment.
Mandal RK., Crane RJ., Berkley JA., Gumbi W., Wambua J., Ngoi JM., Ndungu FM., Schmidt NW.
Background: Gut microbiota were recently shown to impact malaria disease progression and outcome, and prior studies have shown that Plasmodium infections increase the likelihood of enteric bacteria causing systemic infections. Currently, it is not known if Plasmodium infection impacts human gut microbiota as a prelude to bacteremia, or whether antimalarials effect gut microbiota. Our goal was to determine to what degree Plasmodium infections and antimalarial treatment affect human gut microbiota. Methods: 100 Kenyan infants underwent active surveillance for malaria from birth to ten months of age. Each malaria episode was treated with artemether/lumefantrine (AL). Any other treatments, including antibiotics, were recorded. Stool samples were collected on an approximate bi-weekly basis. Ten children were selected on the basis of stool samples having been collected before (n=27) or after (n=17) a malaria episode, and without antibiotics having been administered between collections. These samples were subjected to 16S rRNA gene (V3-V4 region) sequencing. Results: Bacterial community network analysis revealed no obvious differences in the before and after malaria/AL samples, which was consistent with no difference in alpha and beta diversity and taxonomic analysis at the family and genus level with one exception. At the sequence variant (SV) level, akin to bacterial species, only one of the top 100 SVs was significantly different. Additionally, predicted metagenome analysis revealed no significant difference in metagenomic capacity between before and after malaria/AL samples. Intriguingly, number of malaria episodes, one versus two, explained significant variation in gut microbiota composition of the infants. Conclusions: In-depth bioinformatics analysis of stool bacteria has revealed for the first time that human malaria episode/AL treatment have minimal effects on gut microbiota in Kenyan infants.