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.
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References
- Development Initiatives . Global nutrition report 2017: nourishing the SDGs. Bristol: Development Initiatives; 2017.
- 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.
- 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.
- Save the Children . Malnutrition in Bangladesh: Harnessing social protection for the most vulnerable. 2015.
- 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.
- 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.
- National Guidelines for the Facility-based Management of Children with Severe Acute Malnutrition in Bangladesh. 2017. . Accessed 13 Feb 2020.
- 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.
- 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.
- 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