Gut microbiome associations with acute malnutrition relapse in South Sudan

Severe acute malnutrition (SAM) is a leading cause of childhood morbidity and mortality that is defined by anthropometric measurements, weight-for-height z score, and mid-upper arm circumference (MUAC) falling significantly below healthy standards. While treatments for SAM and our understanding of this disease have advanced, children experiencing SAM frequently relapse to acute malnutrition (AM) following anthropometric recovery. Little is known about the contribution of the gut microbiome to AM relapse. We hypothesized that features of the gut microbiome, including microbial composition, antimicrobial resistance gene carriage, and predicted microbial functional pathways, of children discharged from treatment for uncomplicated SAM in South Sudan, may be associated with AM relapse at 1-month follow-up. Overall, broad microbiome profiles at discharge were not associated with AM relapse. We evaluated the associations of microbiome features with AM relapse 1-month post-recovery using mixed linear effect models. We identified associations between higher MUAC, which may be a proxy for future health trajectories, and increased Sutterella wadsworthensis and trimethoprim-resistant dihydrofolate reductase antimicrobial resistance genes. These findings suggest that the gut microbiome at discharge of children treated for uncomplicated SAM has limited predictive value as a standalone diagnostic tool for identifying relapse risk at 1 month.IMPORTANCESevere acute malnutrition (SAM) is a devastating illness that impacts the morbidity and mortality of millions of children worldwide. Community-based management of acute malnutrition (CMAM) is the standard of care in South Sudan and many other low-resource settings for children presenting with SAM. Despite this intervention, children treated for SAM under CMAM frequently relapse to acute malnutrition (AM) following treatment. With advancements in our understanding of malnutrition, there has been a strong and growing interest in developing microbiome-based strategies to treat, prevent, and predict relapse to AM following treatment for SAM. Our work characterizes gut microbiome features of children from a geographic area that is traditionally underrepresented in gut microbiome research and shows that in isolation, a child's gut microbiome at discharge likely holds low predictive value for relapse to AM post-CMAM treatment; however, we identified key microbes and microbial features meriting further research.