An Alternative Oat-Containing, Ready-To-Use, Therapeutic Food Does Not Alter Intestinal Permeability or the 16S Ribosomal RNA Fecal Microbiome Configuration Among Children With Severe Malnutrition in Sierra Leone: A Randomized Controlled Trial.

BACKGROUND: Previously, a novel oat ready-to-use therapeutic food (o-RUTF) resulted in improved recovery from severe acute malnutrition (SAM) when compared to a standard RUTF (s-RUTF). The o-RUTF contained 18% oat, while the s-RUTF has no cereal ingredients. OBJECTIVES: We determined the effects of o-RUTF on intestinal permeability, as measured by lactulose permeability, and the 16S ribosomal RNA (rRNA) fecal microbiome configuration of children with SAM. METHODS: This was a prospective, randomized, double-blinded, controlled clinical trial. Sierra Leonean children aged 6-59 mo with SAM, defined by a midupper arm circumference < 11.5 cm, were randomized to receive o-RUTF or s-RUTF. All children received 7 d of amoxicillin per guidelines. Lactulose permeability testing and fecal 16S rRNA sequencing were performed at baseline and after 4 wk of therapy. The change in lactulose permeability was the primary outcome, while the fecal 16S rRNA configuration at 4 wk was a secondary outcome. RESULTS: Of the 129 children enrolled, lactulose permeability testing was completed by 100 at baseline and 82 at week 4. After 4 wk of therapeutic feeding, there were no differences in lactulose permeability between the o-RUTF and s-RUTF groups (P = 0.84), and over half of children had increased lactulose permeability (50% s-RUTF compared with 58% o-RUTF, mean difference = -7.5%; 95% CI: -29.2, 15.2; P = 0.50). After 4 wk of feeding, there were no differences in the 16S rRNA configurations between the o-RUTF and s-RUTF groups (Permanova, 999 permutations; P = 0.648; pseudo-F = 0.581), nor were there differences in α or ß diversity. CONCLUSIONS: Despite remarkably different compositions of o-RUTF and s-RUTF, no differences were identified in lactulose permeability or the fecal 16S rRNA configuration among children with SAM receiving these foods. These results suggest that the o-RUTF exerts its beneficial effects through mechanisms other than reducing intestinal permeability or altering the fecal 16S configuration. This trial was registered at clinicaltrials.gov as NCT04334538.

The Impact of Milk on Gut Permeability, Fecal 16S rRNA Gene Microbiota Profiling, and Fecal Metabolomics in Children with Moderate Malnutrition in Sierra Leone: A Double-Blind, Randomized Controlled Trial.

BACKGROUND: Bovine milk is a beneficial ingredient in teh treatment of malnutrition. OBJECTIVES: Our objectives were to determine the effect of dietary milk protein and milk carbohydrate on the intestinal permeability, fecal 16S rRNA gene configuration, and fecal metabolomics of children with moderate malnutrition. METHODS: This was a randomized, double-blind, controlled trial among 413 children with wasting in rural Sierra Leone who received 1 of the following 4 supplementary foods, which differed in sources of protein and carbohydrate: milk protein and milk carbohydrate (MPMC), milk protein and vegetable carbohydrate (MPVC), vegetable protein and milk carbohydrate (VPMC), or a control group consuming entirely vegetable-based food (VPVC). After 4 wk, urine and stool were collected from participants enrolled with mid-upper arm circumference of <12.1 cm. Urine was analyzed for lactulose excretion (%L). Stool samples were subjected to both 16S rRNA gene analysis to assess ß-diversity and untargeted metabolomic abundance. RESULTS: Among the 386 children who completed permeability testing, the mean difference (95% CI) in %L excretion as compared with VPVC was 0.01 (-0.05, 0.07) for MPMC, 0.05 (-0.01, 0.11) for MPVC, and 0.01 (-0.05, 0.07) for VPMC. Of the 374 children who provided a stool sample that was analyzed, the ß-diversity among bacterial taxa was similar between dietary groups (P > 0.05 for all comparisons). No significant differences between dietary groups were seen among the 20 most abundant bacterial taxa. Among the 5769 unique metabolomic features identified, greater flavonoid levels in VPVC were seen. CONCLUSIONS: Abnormal intestinal permeability do not improve with 4 wk of supplementary feeding. Fecal rRNA do not differ with consumption of different diets. This trial was registered at clinicaltrials.gov as NCT04216043.