부산대학교 도서관

Frequent enteric infections in children may be an important cause of growth faltering; however, we do not fully understand the mechanisms by which pathogen infections and the physiological responses to these infections result in poorer growth. Commonly used protein fecal biomarkers (anti-alpha trypsin, neopterin, and myeloperoxidase) provide broad immunological information on an inflammatory response; however, they do not provide information on non-immune processes (e.g., gut integrity) that may be important indicators of chronic end states such as environmental enteric dysfunction (EED). To explore how additional biomarkers will better inform which physiological pathways (both immune and non-immune) are impacted by pathogen exposure we added to the traditional panel of 3 protein fecal biomarkers 4 novel fecal mRNA transcript biomarkers (sucrase isomaltase, caudal homeobox 1, S100A8, and mucin 12) and analyzed stool samples from infants living in informal settlements in Addis Ababa, Ethiopia. To test how this expanded biomarker panel captures distinct pathogen exposure processes we used two different scoring systems. First, we used a theory-based approach to assign each biomarker to specific physiological attributes based on prior understanding of each biomarker. Second, we used data reduction methods to categorize biomarkers and then assign physiological attributes to those categories. We used linear models to examine the association between the derived biomarker scores (based on mRNA and protein levels) and stool pathogen gene counts to determine pathogen specific effects on gut physiology and immune responses. Inflammation scores were positively associated with Shigella and enteropathogenic E.Coli (EPEC) infection, while gut integrity scores were negatively associated with Shigella, EPEC and, shigatoxigenic E.coli (STEC) infection. Our expanded panel of biomarkers hold promise as tools to measure systemic outcomes of enteric pathogen infection. mRNA biomarkers complement established protein biomarkers by providing important cell-specific physiological and immunological consequences of pathogen carriage that can lead to chronic end states such as EED. Author summary: Frequent enteric infections in children may be an important cause of growth faltering. Mechanisms by which pathogen infections result in poorer growth, however, are not fully understood. Commonly used biomarkers provide information on broad immunological processes but not on non-immune processes (e.g., gut integrity) that may be important indicators of overall health. In this manuscript we explore how additional biomarkers can expand our understanding on which immune and non-immune pathways are impacted by pathogen exposure. To do this we developed a panel consisting of 3 commonly used and 4 novel biomarkers. We analyzed stool samples from infants living in informal settlements in Addis Ababa, Ethiopia. To test how this expanded biomarker panel captures distinct pathological processes we used two scoring systems and examined their association with stool pathogen gene counts. We found that Shigella and enteropathogenic E. Coli (EPEC) were positively associated in inflammation, while the integrity of intestinal tissue was negatively associated with Shigella, EPEC and shigatoxigenic E.coli (STEC) infection. Our biomarker panel holds promise as a tool to measure both immune and non-immune outcomes of pathogen infection. [ABSTRACT FROM AUTHOR]