Interactions between fecal gut microbiome, enteric pathogens, and energy regulating hormones among acutely malnourished rural Gambian children
Helen M. Nabwera,
Josh L. Espinoza,
Archibald Worwui,
Modupeh Betts,
Catherine Okoi,
Abdul K. Sesay,
Rowan Bancroft,
Schadrac C. Agbla,
Sheikh Jarju,
Richard S. Bradbury,
Mariama Colley,
Amadou T. Jallow,
Jie Liu,
Eric R Houpt,
Andrew M. Prentice,
Martin Antonio,
Robin M Bernstein,
Christopher L. Dupont,
Brenda A. Kwambana-Adams
Affiliations
Helen M. Nabwera
Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, L3 5QA, UK
Josh L. Espinoza
J. Craig Venture Institute, 4120 Capricorn Ln, La Jolla, CA 92037, USA; Applied Sciences, Durban University of Technology, Durban, South Africa
Archibald Worwui
Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Fajara, Banjul, PO Box 273, The Gambia
Modupeh Betts
NIHR Global Health Research Unit on Mucosal Pathogens, Division of Infection and Immunity, University College London, London, United Kingdom
Catherine Okoi
Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Fajara, Banjul, PO Box 273, The Gambia
Abdul K. Sesay
Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Fajara, Banjul, PO Box 273, The Gambia
Rowan Bancroft
Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Fajara, Banjul, PO Box 273, The Gambia
Schadrac C. Agbla
Department of Health Data Science, University of Liverpool, Liverpool, UK
Sheikh Jarju
Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Fajara, Banjul, PO Box 273, The Gambia
Richard S. Bradbury
School of Health and Life Sciences, Federation University
Mariama Colley
Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Fajara, Banjul, PO Box 273, The Gambia
Amadou T. Jallow
Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Fajara, Banjul, PO Box 273, The Gambia
Jie Liu
Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, United States of America
Eric R Houpt
Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia, United States of America
Andrew M. Prentice
Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Fajara, Banjul, PO Box 273, The Gambia
Martin Antonio
Medical Research Council Unit The Gambia at London School of Hygiene and Tropical Medicine, Fajara, Banjul, PO Box 273, The Gambia; Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK
Robin M Bernstein
Growth and Development Lab, Department of Anthropology, University of Colorado, Boulder, CO, United States of America
Christopher L. Dupont
J. Craig Venture Institute, 4120 Capricorn Ln, La Jolla, CA 92037, USA; Corresponding: Dr Brenda Anna Kwambana-Adams, Christopher L. Dupont
Brenda A. Kwambana-Adams
NIHR Global Health Research Unit on Mucosal Pathogens, Division of Infection and Immunity, University College London, London, United Kingdom; Corresponding: Dr Brenda Anna Kwambana-Adams, Christopher L. Dupont
Background: The specific roles that gut microbiota, known pathogens, and host energy-regulating hormones play in the pathogenesis of non-edematous severe acute malnutrition (marasmus SAM) and moderate acute malnutrition (MAM) during outpatient nutritional rehabilitation are yet to be explored. Methods: We applied an ensemble of sample-specific (intra- and inter-modality) association networks to gain deeper insights into the pathogenesis of acute malnutrition and its severity among children under 5 years of age in rural Gambia, where marasmus SAM is most prevalent. Findings: Children with marasmus SAM have distinct microbiome characteristics and biologically-relevant multimodal biomarkers not observed among children with moderate acute malnutrition. Marasmus SAM was characterized by lower microbial richness and biomass, significant enrichments in Enterobacteriaceae, altered interactions between specific Enterobacteriaceae and key energy regulating hormones and their receptors. Interpretation: Our findings suggest that marasmus SAM is characterized by the collapse of a complex system with nested interactions and key associations between the gut microbiome, enteric pathogens, and energy regulating hormones. Further exploration of these systems will help inform innovative preventive and therapeutic interventions. Funding: The work was supported by the UK Medical Research Council (MRC; MC-A760-5QX00) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement; Bill and Melinda Gates Foundation (OPP 1066932) and the National Institute of Medical Research (NIMR), UK. This network analysis was supported by NIH U54GH009824 [CLD] and NSF OCE-1558453 [CLD].
