Gut Microbiota in Military International Travelers with Doxycycline Malaria Prophylaxis: Towards the Risk of a Simpson Paradox in the Human Microbiome Field

Dysbiosis, developed upon antibiotic administration, results in loss of diversity and shifts in the abundance of gut microbes. Doxycycline is a tetracycline antibiotic widely used for malaria prophylaxis in travelers. We prospectively studied changes in the fecal microbiota of 15 French soldiers after a 4-month mission to Mali with doxycycline malaria prophylaxis, compared to changes in the microbiota of 28 soldiers deployed to Iraq and Lebanon without doxycycline. Stool samples were collected with clinical data before and after missions, and 16S rRNA sequenced on MiSeq targeting the V3-V4 region. Doxycycline exposure resulted in increased alpha-biodiversity and no significant beta-dissimilarities. It led to expansion in Bacteroides, with a reduction in Bifidobacterium and Lactobacillus, as in the group deployed without doxycycline. Doxycycline did not alter the community structure and was specifically associated with a reduction in Escherichia and expression of Rothia. Differences in the microbiota existed at baseline between military units but not within the studied groups. This group-effect highlighted the risk of a Simpson paradox in microbiome studies.