Gut microbiome in Ethiopia: Gut microbiome dynamics in childhood diarrhea, enteric infections and malnutrition in Ethiopian children below the age of five years

Diarrhea and acute malnutrition are significant contributors to childhood morbidity and mortality in low- and middle-income countries (LMICs). More than 90% of these cases occur in Sub-Saharan Africa and Southeast Asia, where diarrhea and acute malnutrition often coexist and exacerbate each other, increasing the risk of enteric infections, comorbidities, and mortality.

In recent decades, extensive metagenomic data has revealed the critical role of gut microbiota (GM) in health and disease. A balanced and diverse GM is essential for human health, aiding in dietary metabolism, vitamin synthesis, immune regulation, and pathogen resistance. Conversely, an imbalanced GM can lead to harmful effects like diarrhea, acute malnutrition, and increased susceptibility to enteric infections.

During this PhD project, we studied the GM of Ethiopian children under five with diarrhea, Giardia infection, and severe acute malnutrition (SAM) and found associations with GM diversity and compositional changes. Children with diarrhea had lower bacterial diversity and were enriched in putative pathogens like Escherichia spp., Campylobacter spp., and Streptococcus spp. They were also depleted in gut commensals such as Prevotella copri, Faecalibacterium prausnitzii, and Dialister succinatiphilus, with greater depletion in prolonged diarrhea cases, suggesting that loss of gut commensals may contribute to the progression from acute to prolonged diarrhea. Furthermore, Giardia-infection and higher Giardia pathogen burden were significantly associated with higher GM diversity and largescale GM compositional changes, regardless of diarrhea status and duration. Giardiainfection seemed to promote the expansion of potent short-chain fatty acid (SCFA) producing taxa such as P. copri, F. prausnitzii, and D. succinatiphilus, while depleting potential pathogenic taxa like Escherichia spp. The Giardia pathogen burden was negatively associated with Escherichia spp. We also observed that the GM of children with SAM was enriched in putative pathogens such as Escherichia spp. and Campylobacter spp., with a reduction in obligate anaerobes. Fecal samples collected after treatment with ready-to-use therapeutic food (RUTF) and antibiotics showed an immature GM compared to admission samples, indicating that RUTF alone is insufficient to repair the immature GM in children with SAM.

These findings highlight the importance of considering the role of the GM when designing interventions aimed at improving health outcomes for children with diarrhea, Giardia infection, and SAM.