Plasma lipopolysaccharide levels predict mortality in acutely ill children in Low- and Middle-Income Countries

Childhood mortality remains high in low-resource settings, where environmental enteric dysfunction (EED) is prevalent. Peripheral blood bacterial lipopolysaccharides (LPS) are potential biomarkers of intestinal microbial translocation and inflammation; however, the effects of LPS translocation on mortality in this context remains unexplored. We investigate the association between plasma LPS and mortality among 638 acutely ill hospitalised children and compare them to 251 well community peers in a nested case-cohort (NCC) conducted between November 2016 and January 2019 across 9 sites in 6 countries in sub-Saharan Africa and South Asia. Higher levels of plasma LPS and inflammatory biomarkers (fecal calprotectin, plasma myeloperoxidase, and CD14) are associated with elevated 90-day mortality, and those associations are independent of wasting status. Non-survivors with high plasma LPS exhibit elevated gram-negative enteric microbiota, increased fecal biomarkers of EED, systemic inflammatory proteins, and differentially expressed proteins linked to the Insulin-like growth factor (IGF) nutritional axis, Interleukin-1 and collagen regeneration. Cellular interaction network models deconvoluted from a single-cell transcriptomic dataset enable an exploratory investigation of systemic immune responses and epithelial-immune cells crosstalk active in pathways leading to mortality. This knowledge can guide the identification of potential therapeutic signaling pathways in settings with high EED and malnutrition.

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Publication Details

Journal
Nature Communications
Published
2025-11-28
DOI
https://doi.org/10.1038/s41467-025-65429-0
Citations
2
Primary Topic
Gut microbiota and health
Type
article
Field-Weighted Citation Impact
1.61

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article

Plasma lipopolysaccharide levels predict mortality in acutely ill children in Low- and Middle-Income Countries

Kelsey Jones, Dilruba Ahmed, Abu Sadat Mohammad Sayeem Bin Shahid, Robert Bandsma et al.
2 citations
Nature Communications
Gut microbiota and health
1.61
article

Plasma lipopolysaccharide levels predict mortality in acutely ill children in Low- and Middle-Income Countries

Kelsey Jones, Dilruba Ahmed, Abu Sadat Mohammad Sayeem Bin Shahid, Robert Bandsma, Christina Lancioni, Lisa Gartner, Christopher Allen, James Alexander Berkley, Caroline Tigoi, Judd L. Walson, James M. Njunge, Agnes Gwela, Wieger P. Voskuijl, Ezekiel Mupere, Abdoulaye Hama Diallo, Zaubina Kazi, Arya Ghate, Holm H. Uhlig, Kirkby D. Tickell, Ali Faisal Saleem, Benson O. Singa, Mohammod Jobayer Chisti, Wilson Gumbi, Tahmeed Ahmed
article en
2 citations

Abstract

Childhood mortality remains high in low-resource settings, where environmental enteric dysfunction (EED) is prevalent. Peripheral blood bacterial lipopolysaccharides (LPS) are potential biomarkers of intestinal microbial translocation and inflammation; however, the effects of LPS translocation on mortality in this context remains unexplored. We investigate the association between plasma LPS and mortality among 638 acutely ill hospitalised children and compare them to 251 well community peers in a nested case-cohort (NCC) conducted between November 2016 and January 2019 across 9 sites in 6 countries in sub-Saharan Africa and South Asia. Higher levels of plasma LPS and inflammatory biomarkers (fecal calprotectin, plasma myeloperoxidase, and CD14) are associated with elevated 90-day mortality, and those associations are independent of wasting status. Non-survivors with high plasma LPS exhibit elevated gram-negative enteric microbiota, increased fecal biomarkers of EED, systemic inflammatory proteins, and differentially expressed proteins linked to the Insulin-like growth factor (IGF) nutritional axis, Interleukin-1 and collagen regeneration. Cellular interaction network models deconvoluted from a single-cell transcriptomic dataset enable an exploratory investigation of systemic immune responses and epithelial-immune cells crosstalk active in pathways leading to mortality. This knowledge can guide the identification of potential therapeutic signaling pathways in settings with high EED and malnutrition.

Nature CommunicationsVol. 16(1)
Aga Khan University (PK), Université Joseph Ki-Zerbo (BF), Centre for Human Genetics (GB), Johns Hopkins University (US), Oregon Health & Science University (US), University of Washington (US), International Centre for Diarrhoeal Disease Research (BD), Johns Hopkins Medicine (US), Great Ormond Street Hospital (GB), Kamuzu Central Hospital (MW), Hospital for Sick Children (CA), Kenya Medical Research Institute (KE), University of Oxford (GB), Emma Kinderziekenhuis (NL), Amsterdam Institute for Global Health and Development (NL), Oxford BioMedica (United Kingdom) (GB), The Childhood Acute Illness and Nutrition Network (KE), Centre Muraz (BF), Kamuzu University of Health Sciences (MW), University College London (GB), Seattle University (US), Makerere University (UG), University of Amsterdam (NL)
Bill and Melinda Gates Foundation, Wellcome Trust, National Institute for Health and Care Research, NIHR Oxford Biomedical Research Centre
Openalex Percentile: Top 14%
Gut microbiota and health
1.61
DOIOpen Access PDFOpenAlex
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