Journal Article

Intestinal disturbances associated with mortality of children with complicated severe malnutrition

Mwalekwa, Laura, Walson, Judd L., Farooqui, Amber, Bourdon, Celine, Chimwezi, Emmanuel, Ngari, Moses, Thitiri, Johnstone, Bandsma, Robert H. J., Voskuijl, Wieger, Berkley, James A., Tarafdar, Nawar, Wen, Bijun

2023

Overview

Background Children admitted to hospital with complicated severe malnutrition (CSM) have high mortality despite compliance with standard WHO management guidelines. Limited data suggests a relationship between intestinal dysfunction and poor prognosis in CSM, but this has not been explicitly studied. This study aimed to evaluate the role of intestinal disturbances in CSM mortality. Methods A case-control study nested within a randomized control trial was conducted among children hospitalized with CSM in Kenya and Malawi. Children who died (cases, n  = 68) were compared with those who were discharged, propensity matched to the cases on age, HIV and nutritional status (controls, n  = 68) on fecal metabolomics that targeted about 70 commonly measured metabolites, and enteropathy markers: fecal myeloperoxidase (MPO), fecal calprotectin, and circulating intestinal fatty acid binding protein (I-FABP). Results The fecal metabolomes of cases show specific reductions in amino acids, monosaccharides, and microbial fermentation products, when compared to controls. SCFA levels did not differ between groups. The overall fecal metabolomics signature moderately differentiates cases from controls (AUC = 0.72). Enteropathy markers do not differ between groups overall, although serum I-FABP is elevated in cases in a sensitivity analysis among non-edematous children. Integrative analysis with systemic data suggests an indirect role of intestinal inflammation in the causal path of mortality. Conclusions Intestinal disturbances appear to have an indirect association with acute mortality. Findings of the study improve our understanding of pathophysiological pathways underlying mortality of children with CSM. Plain Language Summary Malnourished children are at a high risk of dying when exposed to an acute illness. They often have symptoms like diarrhea that indicate their gut is not working properly. It is unclear whether these gut problems contribute to their deaths. Feces contain numerous small molecules processed by the gut that reflect gut health. We compare these fecal molecules between malnourished children who died during hospitalization to those who survived, and relate them to signs of inflammation in the body. We show that the fecal molecules are different between children who died and those who survived. These differences reveal that poor gut health could increase risk of death, potentially by perturbing the body’s defensive response to an acute illness. These findings underscore that treatment for ill severely malnourished children should focus on improving gut health. Wen et al. investigate associations between intestinal disturbances and mortality in children hospitalized with complicated severe malnutrition. Differences are seen in the fecal metabolome of children who die compared with those who are discharged, with integrative analyses suggesting an indirect role for intestinal inflammation in mortality.

• Publisher: Nature Publishing Group UK,Springer Nature B.V,Nature Portfolio
• Subject: 692/308/3187 / 692/4020/1503 / 692/699/1702/295 / 82/6 / Age / Child mortality / Diarrhea / Feces / Hospitals / Inflammation / Malnutrition / Medicine / Medicine & Public Health / Metabolites / Microbiota / Mortality / NMR / Nuclear magnetic resonance / Regression analysis / Sample size