Intestinal disturbances associated with mortality of children with complicated severe malnutrition
Abstract 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...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-023-00355-0 |
| _version_ | 1797556963428532224 |
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| author | Bijun Wen Amber Farooqui Celine Bourdon Nawar Tarafdar Moses Ngari Emmanuel Chimwezi Johnstone Thitiri Laura Mwalekwa Judd L. Walson Wieger Voskuijl James A. Berkley Robert H. J. Bandsma |
| author_facet | Bijun Wen Amber Farooqui Celine Bourdon Nawar Tarafdar Moses Ngari Emmanuel Chimwezi Johnstone Thitiri Laura Mwalekwa Judd L. Walson Wieger Voskuijl James A. Berkley Robert H. J. Bandsma |
| author_sort | Bijun Wen |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-10T17:09:28Z |
| format | Article |
| id | doaj.art-ee4ec22ff3ee4d6aafaa72fdad5a8e33 |
| institution | Directory Open Access Journal |
| issn | 2730-664X |
| language | English |
| last_indexed | 2024-03-10T17:09:28Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj.art-ee4ec22ff3ee4d6aafaa72fdad5a8e332023-11-20T10:42:35ZengNature PortfolioCommunications Medicine2730-664X2023-09-013111010.1038/s43856-023-00355-0Intestinal disturbances associated with mortality of children with complicated severe malnutritionBijun Wen0Amber Farooqui1Celine Bourdon2Nawar Tarafdar3Moses Ngari4Emmanuel Chimwezi5Johnstone Thitiri6Laura Mwalekwa7Judd L. Walson8Wieger Voskuijl9James A. Berkley10Robert H. J. Bandsma11Department of Nutritional Sciences, Faculty of Medicine, University of TorontoDepartment of Translational medicine, Hospital for Sick ChildrenDepartment of Translational medicine, Hospital for Sick ChildrenDepartment of Translational medicine, Hospital for Sick ChildrenThe Childhood Acute Illness & Nutrition NetworkThe Childhood Acute Illness & Nutrition NetworkThe Childhood Acute Illness & Nutrition NetworkKEMRI/Wellcome Trust Research ProgrammeThe Childhood Acute Illness & Nutrition NetworkThe Childhood Acute Illness & Nutrition NetworkThe Childhood Acute Illness & Nutrition NetworkDepartment of Nutritional Sciences, Faculty of Medicine, University of TorontoAbstract 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.https://doi.org/10.1038/s43856-023-00355-0 |
| spellingShingle | Bijun Wen Amber Farooqui Celine Bourdon Nawar Tarafdar Moses Ngari Emmanuel Chimwezi Johnstone Thitiri Laura Mwalekwa Judd L. Walson Wieger Voskuijl James A. Berkley Robert H. J. Bandsma Intestinal disturbances associated with mortality of children with complicated severe malnutrition Communications Medicine |
| title | Intestinal disturbances associated with mortality of children with complicated severe malnutrition |
| title_full | Intestinal disturbances associated with mortality of children with complicated severe malnutrition |
| title_fullStr | Intestinal disturbances associated with mortality of children with complicated severe malnutrition |
| title_full_unstemmed | Intestinal disturbances associated with mortality of children with complicated severe malnutrition |
| title_short | Intestinal disturbances associated with mortality of children with complicated severe malnutrition |
| title_sort | intestinal disturbances associated with mortality of children with complicated severe malnutrition |
| url | https://doi.org/10.1038/s43856-023-00355-0 |
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