Modifying Intestinal Integrity and Microbiome in Children Hospitalised with Severe and Complicated Malnutrition Using Legume-Based Feeds [MIMBLE]: Proof of Principle Trial

Abstract

Outcomes in African children hospitalised with severe acute malnutrition (SAM) remain poor. Evidence suggests disordered gastrointestinal function that is supported by our findings of raised baseline lactulose:mannitol ratio, high calprotectin and measures of satiety (polypeptide YY).  We hypothesised that nutritional feeds should be designed to promote bacterial diversity and restore GI barrier function, since current feeding regimens have little effect on this, as demonstrated in our study. A 3-arm pilot trial in 58 Ugandan children with SAM examined two experimental nutritional strategies: standard feeds enriched with cowpea flour (CpF), or inulin (InF) versus control standard feeds (ConF) and followed for 28 days supports our hypothesis. We showed CpF-enriched was safe, effective (weight-gain, Day-28 mortality) and ameliorated antibiotic-mediated decrease in gut microbiota diversity from day 1-7, observed in both ConF and InF groups. Additionally, we demonstrated a significant increase in Bifidobacterium from day 7 to day 28 in the CpF group.

Keywords: Severe acute malnutrition, African children, nutritional feeds, Clinical trial, gut barrier dysfunction, short chain fatty acid, gut hormones, NMR spectroscopy, 16S, microbiome, metabolome