Gut microbiota patterns associated with duration of diarrhea in children under five years of age in Ethiopia

Diarrhea claims about 500,000 lives annually among children under five years of age, in low- and middle-income countries (LMICs). Childhood mortality due to acute diarrhea (AD; less than 7 days of duration) is decreasing, but prolonged (ProD; 7-13 days of duration) and persistent (PD; greater than or equal to 14 days of duration) diarrhea combined (ProPD) are responsible for increased morbidity and mortality in LMICs. We aimed to decipher if gut microbiota (GM) compositional differences between children with AD, ProPD, and non-diarrheal controls is linked to ProPD etiology. We analyzed the GM of 1313 Ethiopian children under five years of age comparing 554 AD cases, 95 ProPD cases, and 663 frequency matched, non-diarrheal controls by 16S rRNA gene (V4 region) amplicon sequencing. We found diarrhea cases were associated a lower in bacterial diversity compared to non-diarrheal controls and enriched in Escherichia spp., Campylobacter spp., and Streptococcus spp. Further, they were depleted in commensals Prevotella copri, Faecalibacterium prausnitzii, and Dialister succinatiphilus. Compared to AD cases, ProPD cases were characterized by a further depletion of gut commensals like F. prausnitzii, Akkermansia muciniphila and Blautia spp. Our results demonstrated the GM of children with ProPD was characterized by a pronounced reduction of obligate anaerobic gut commensals compared to AD, suggesting that prolonged duration of diarrhea is accompanied with a depletion of healthy gut commensals. This indicates a potential role for targeted dietary supplements to restore gut eubiosis and/ or the use of next-generation probiotics to improve ProPD treatment. Keywords: Acute diarrhea (AD), prolonged or persistent diarrhea (ProPD), gut microbiota, gut dysbiosis, children, Ethiopia.