Systemic inflammation and metabolic disturbances underlie inpatient mortality among ill children with severe malnutrition

Bijun Wen, James M. Njunge, Celine Bourdon, Gerard Bryan Gonzales, Bonface M. Gichuki, Dorothy Lee, David S. Wishart, Moses Ngari, Emmanuel Chimwezi, Johnstone Thitiri, Laura Mwalekwa, Wieger Voskuijl, James A. Berkley, Robert H. J. Bandsma

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Children admitted to hospital with an acute illness and concurrent severe malnutrition [complicated severe malnutrition (CSM)] have a high risk of dying. The biological processes underlying their mortality are poorly understood. In this case-control study nested within a multicenter randomized controlled trial among children with CSM in Kenya and Malawi, we found that blood metabolomic and proteomic profiles robustly differentiated children who died (n = 92) from those who survived (n = 92). Fatalities were characterized by increased energetic substrates (tricarboxylic acid cycle metabolites), microbial metabolites (e.g., propionate and isobutyrate), acute phase proteins (e.g., calprotectin and C-reactive protein), and inflammatory markers (e.g., interleukin-8 and tumor necrosis factor–α). These perturbations indicated disruptions in mitochondria-related bioenergetic pathways and sepsis-like responses. This study identified specific biomolecular disturbances associated with CSM mortality, revealing that systemic inflammation and bioenergetic deficits are targetable pathophysiological processes for improving survival of this vulnerable population.
Original languageEnglish
Article numbereabj6779
JournalScience advances
Volume8
Issue number7
DOIs
Publication statusPublished - 1 Feb 2022

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