Bednarski : Stool microbiome in Ugandan children is associated with differential malaria outcomes
Stool microbiome in Ugandan children is associated with differential malaria outcomes.
Indiana University School of Medicine
Olivia Bednarski1, Ruth Namazzi2, Robert Opoka2, Chandy John3, and Nathan Schmidt3
1 Department of Microbiology and Immunology, Indiana University, Indianapolis, IN, 2 Department of Paediatrics and Child Health, Makerere University, Kampala, Uganda, 3 Ryan White Center for Pediatric Infectious Diseases and Global Health, Department of Pediatrics, Indiana University, Indianapolis, IN
Gut microbiota in mice modulates the severity of malaria by regulating the humoral immune response to Plasmodium. It is presently unknown if gut microbiota also impacts the severity of malaria in humans. This study sought to assess if the composition of the gut microbiota differentially affects the development of severe malaria in Ugandan children infected with P. falciparum.
We sequenced the bacterial 16S rRNA gene in over 500 stool samples from <5-year-old Ugandan children with five clinically distinct severe malaria presentations (prostration, severe malaria anemia, multiple seizures, respiratory distress, and cerebral malaria), and healthy community children (consisting of both P. falciparum negative and asymptomatic P. falciparum positive children).
When assessing alpha diversity, asymptomatic and community children had greater richness and evenness compared to children that developed severe malaria. Beta diversity analysis demonstrated significant dissimilarity in stool bacteria communities between each severe malaria subgroup and asymptomatic children. Differential abundance testing revealed a single bacteria species as consistently enriched in all severe malaria subgroups. Additionally, longitudinal analysis over twelve months revealed specific bacteria were enriched in the community children that subsequently developed severe malaria.
Our data provide the first demonstration that specific gut bacteria are associated with the severity of malaria in African children. With this preliminary evidence, it is substantiated to investigate further the connection between the gut microbiota as another risk factor for the development of severe disease in malaria. Ongoing experiments include metagenomic sequencing of stool samples and causative experiments with mice.
Translational/Human Health Impact:
This may lay the groundwork for the development of probiotic or oral antibiotic therapies to better control P. falciparum infection in African children.