Association of Intestinal Alkaline Phosphatase and vitamin D level with enteric pathogens in children: results from the MAL-ED study in Bangladesh

ObjectiveIntestinal Alkaline Phosphatase (IAP), expressed by enterocytes, maintains gut homeostasis by promoting commensal microbiota growth and limiting inflammation. Vitamin D strengthens intestinal barrier, and its deficiency is linked to various diseases. This study explores the relationship among IAP, vitamin D, and enteric pathogens in children. MethodsIn the MAL-ED (Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development) study, 265 newborns were enrolled between February 2010 to February 2012, from Dhaka, Bangladesh. 15-month time point data was collected and analyses, where intestinal pathogens were identified by TaqMan Array Card assay, stool IAP and serum vitamin D level were determined by colorimetric assay and chemiluminescence immunoassay respectively. Multivariable linear regression was performed to determine the association between IAP, vitamin D and gut pathogens. A p-value of <0.05 is considered as significant. ResultsMedian (IQR) of IAP was 55.41 (19.60, 155.41) U/{micro}L. Bivariate analysis showed significant negative association of IAP with Campylobacter-pan Genome (p=0.047), Campylobacter jejuni (p=0.020) and Enterocytozoon bieneusi (p=0.023). Multivariable linear regression analysis revealed a significant and inverse association with the Adenovirus-pan genome ({beta}= -2.00; 95% CI= -3.94, -0.07) and E. bieneusi ({beta}= -3.03; 95% CI= -5.94, -0.11). ConclusionIAP was inversely and significantly associated with Adenovirus-pan genome and E. bieneusi, a less-explored enteric pathogen, while its relationship with vitamin D was positive but not statistically significant. These findings suggest that IAP may play a protective role against specific enteric pathogens. What is already known on this topicO_LIIntestinal Alkaline Phosphatase (IAP) plays a crucial role in maintenance of gut homeostasis by promoting beneficial microbiota and reducing intestinal inflammation. C_LIO_LIVitamin D strengthens the intestinal barrier, and deficiency has been linked to increased risk of infections and various chronic diseases. C_LIO_LIWhile both IAP and vitamin D are important in gut health, evidence linking them with specific enteric pathogens in human, especially in children remains limited. C_LI What this study addsO_LIThis study demonstrates that IAP is inversely and significantly associated with Adenovirus-pan genome and Enterocytozoon bieneusi, a less-explored pathogen in children. C_LIO_LIIt shows that although not statistically significant, IAP levels were positively related to vitamin D C_LIO_LIThese findings provide novel evidence that IAP may play a protective role against specific viral and protozoan enteric infections. C_LI How this study might affect research, practice or policyO_LIThe results highlight IAP as a potential biomarker of intestinal defense and a candidate for future therapeutic or preventive interventions targeting childhood enteric infections. C_LIO_LIInsights into IAP-pathogen relationships could guide in the development of microbiome-based or nutritional strategies to reduce diarrheal disease burden, and support the inclusion of IAP as potential intervention in child health and nutrition research in low-resource settings. C_LI