Proof-of-concept study of the efficacy of a microbiota-directed complementary food formulation (MDCF) for treating moderate acute malnutrition

Ishita Mostafa, Naila Nurun Nahar, Md Munirul Islam, Sayeeda Huq, Mahfuz Mustafa, Michael Barratt, Jeffrey I Gordon, Tahmeed Ahmed, Ishita Mostafa, Naila Nurun Nahar, Md Munirul Islam, Sayeeda Huq, Mahfuz Mustafa, Michael Barratt, Jeffrey I Gordon, Tahmeed Ahmed

Abstract

Background: Childhood undernutrition remains a significant global health challenge accounting for over half of all under 5 child mortality. Moderate acute malnutrition (MAM), which leads to wasting [weight-for-length z-scores (WLZ) between - 2 and - 3], affects 33 million children under 5 globally and more than 2 million in Bangladesh alone. We have previously reported that acute malnutrition in this population is associated with gut microbiota immaturity, and in a small, 1-month pre-proof-of-concept (POC) study demonstrated that a microbiota-directed complementary food formulation (MDCF-2) was able to repair this immaturity, promote weight gain and increase plasma biomarkers and mediators of healthy growth. Here we describe the design controlled feeding study that tests whether MDCF-2 exhibits superior efficacy (ponderal growth, host biomarkers of a biological state) than a conventional Ready-to-use Supplementary Food (RUSF) in children with MAM over intervention period of 3 months.

Methods: Two separate cohorts of 12-18-month-old children will be enrolled: 124 with primary MAM, and 124 with MAM after having been treated for severe acute malnutrition (post-SAM MAM). We have established several field sites in an urban slum located in the Mirpur district of Dhaka, Bangladesh and at a rural site, Kurigram in the north of Bangladesh. The two groups of children receiving MDCF-2 and RUSF will be compared at baseline (pre-intervention), after 1 month, at the end of intervention (3 months), 1 month after cessation of intervention, and every 6 months thereafter for 4 years.

Discussion: This study will determine whether daily, controlled administration of MDCF-2 for 3 months provides superior improvements in weight gain, microbiota repair, and elevated levels of key plasma biomarkers/mediators of healthy growth compared to the control RUSF formulation. The pathogenesis of MAM is poorly defined and there are currently no WHO-approved treatments; results from the current study of children with primary MAM and post-SAM MAM will shed light on the effects of the gut microbiota on childhood growth/development and will provide a knowledge base that may help improve complementary feeding practices.

Trial registration: The primary MAM and post-SAM MAM trials are registered in Clintrials.gov (NCT04015999 and NCT04015986, registered on July 11, 2019, retrospectively registered).

Keywords: Microbiota Directed Complementary Food (MDCF); Moderate acute malnutrition (MAM); Ready to use Supplementary Food (RUSF); Severe acute malnutrition (SAM).

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Design of controlled feeding study, including time points where anthropometric data will be collected and biospecimens obtained. a Trial of children presenting with primary MAM. b Trial of children who present with SAM

References

    1. Development Initiatives . Global nutrition report 2017: nourishing the SDGs. Bristol: Development Initiatives; 2017.
    1. National Institute of Population Research and Training (NIPORT), Mitra and Associates, and ICF International . Bangladesh Demographic and Health Survey 2014. Dhaka, and Rockville: NIPORT, Mitra and Associates, and ICF International; 2016.
    1. World Health Organization, UNICEF . WHO child growth standards and the identification of severe acute malnutrition in infants and children: joint statement by the World Health Organization and the United Nat Nations Children’s Fund. 2009.
    1. Save the Children . Malnutrition in Bangladesh: Harnessing social protection for the most vulnerable. 2015.
    1. Gehrig JL, Venkatesh S, Chang HW, Hibberd MC, Kung VL, Cheng J, Chen RY, Subramanian S, Cowardin CA, Meier MF, O’Donnell D. Effects of microbiota-directed foods in gnotobiotic animals and undernourished children. Science. 2019;365:eaau4732. doi: 10.1126/science.aau4732.
    1. Raman AS, Gehrig JL, Venkatesh S, Chang HW, Hibberd MC, Subramanian S, Kang G, Bessong PO, Lima AA, Kosek MN, Petri WA. A sparse covarying unit that describes healthy and impaired human gut microbiota development. Science. 2019;365:eaau4735. doi: 10.1126/science.aau4735.
    1. National Guidelines for the Facility-based Management of Children with Severe Acute Malnutrition in Bangladesh. 2017. . Accessed 13 Feb 2020.
    1. Koo Terry K., Li Mae Y. A Guideline of Selecting and Reporting Intraclass Correlation Coefficients for Reliability Research. Journal of Chiropractic Medicine. 2016;15(2):155–163. doi: 10.1016/j.jcm.2016.02.012.
    1. Mahfuz M, Das S, Mazumder RN, Rahman MM, Haque R, Bhuiyan MM, Akhter H, Sarker MS, Mondal D, Muaz SS, Karim AB. Bangladesh environmental enteric dysfunction (BEED) study: protocol for a community-based intervention study to validate non-invasive biomarkers of environmental enteric dysfunction. BMJ Open. 2017;7:e017768. doi: 10.1136/bmjopen-2017-017768.
    1. Feng L, Raman AS, Hibberd MC, Cheng J, Griffin NW, Peng Y, Leyn SA, Rodionov DA, Osterman AL, Gordon JI. Identifying determinants of bacterial fitness in a model of human gut microbial succession. Proc Natl Acad Sci USA. 2020;117:2622–2633. doi: 10.1073/pnas.1918951117.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir