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.

Minsoo Son, Marie L Laury, Kevin B Stephenson, Thaddaeus May, D Taylor Hendrixson, Aminata Shamit Koroma, Amara Stevens Ngegbai, Jong Hee Song, Nino Naskidashvili, Young Ah Goo, Mark J Manary

Journal: The American journal of clinical nutrition 2024;120(5):1114-1124

PMID: 39307188

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Plain Language Summary

Milk protein (MP) is considered an ideal dietary protein for children due to its high digestibility and rich essential amino acid profile. Children with acute malnutrition require rapid rebuilding body tissue that is involved in the production of energy and the gut lining, which plays a critical role in nutrient absorption and acts as a barrier to undigested foods and pathogens. This study aimed to compare the effects of four ready-to-use, peanut-based supplementary foods on gut permeability, gut microbiota composition, and biological substances formed during metabolism in children with moderate acute malnutrition. The study was a prospective, randomised, double-blind, controlled trial which enrolled 413 children with wasting. Participants were randomly assigned to one of four groups. Results showed that intestinal permeability was unaffected by 4 weeks of supplementary feeding with milk-containing foods compared to a non-milk-containing alternative. Across all groups, there was no significant change in intestinal permeability after 4 weeks of feeding. The authors concluded that their findings did not determine whether MP or milk carbohydrate (MC) was responsible for any improvements in gut permeability or changes in the microbial/metabolomic milieu. Gut permeability remained unchanged over 4 weeks, and faecal microbiota and metabolites did not reveal consistent patterns of change.

Abstract

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 β-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 β-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.

Address: Mass Spectrometry Technology Access Center at the McDonnell Genome Institute, Washington University, St. Louis, MO, United States.; Genome Technology Access Center, McDonnell Genome Institute, Washington University, St. Louis, MO, United States.; Department of Internal Medicine, Washington University, St. Louis, MO, United States.; Department of Internal Medicine, Baylor College of Medicine, Houston, TX, United States.; Department of Pediatrics, University of Washington, Seattle, WA, United States.; Ministry of Health, The Republic of Sierra Leone, Freetown, Sierra Leon.; Brown School, Washington University, St. Louis, MO, United States.; Department of Pediatrics, Washington University School of Medicine, One Children's Place, Saint Louis, MO, United States; Children's Nutrition Research Center, Baylor College of Medicine, Houston, TX, United States. Electronic address: [email protected].

DOI: 10.1016/j.ajcnut.2024.09.018

Patient Centred Factor

Mediators: Gut-microbiota-metabolome axis

Physical Environment

Infectious Agents

Clinical Imbalances

Gastro-intestinal

Laboratory Testing

Stool Urine

Modifiable Lifestyle Factors

Diet

Jadad Score

Allocation Concealment

Yes

Nutrition Evidence Keywords

Malnutrition Amino acids Weight gain Intestinal permeability Short-chain fatty acid Milk protein Lactose Gut Milk carbohydrate Isoenergetic Disaccharidases

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MeSH Terms: Humans, Feces, Double-Blind Method, RNA, Ribosomal, 16S, Animals, Milk, Female, Sierra Leone, Male, Gastrointestinal Microbiome, Permeability, Child, Preschool, Metabolomics, Infant, Malnutrition, Child