Myeloperoxidase as a biomarker for intestinal-brain axis dysfunction induced by malnutrition and Cryptosporidium infection in weanling mice

Cryptosporidiosis is a waterborne protozoal infection that may cause life-threatening diarrhea in undernourished children living in unsanitary environments. The aim of this study is to iden-tify new biomarkers that may be related to gut-brain axis dysfunction in children suffering from the malnutrition/infection vicious cycle is necessary for better intervention strategies. Myeloperoxidase (MPO) is a well-known neutrophil-related tissue factor released during enter-opathy that could drive gut-derived brain inflammation. We utilized a model of environmental enteropathy in C57BL/6 weanling mice challenged by Cryptosporidium and undernutrition. Mice were fed a 2%-Protein Diet (dPD) for eight days and orally infected with 107-C. parvum oocysts. C. parvum oocyst shedding was assessed from fecal and ileal-extracted genomic DNA by qRT-PCR. Ileal histopathology scores were assessed for intestinal inflammation. Prefrontal cortex samples were snap-frozen for MPO ELISA assay and NF-kb immunostaining. Blood samples were drawn by cardiac puncture after anesthesia and sera were obtained for serum amyloid A (SAA) and MPO analysis. Brain samples were also obtained for Iba-1 prefrontal cortex immu-nostaining. C. parvum-infected mice showed sustained stool oocyst shedding for six days post -infection and increased fecal MPO and inflammation scores. dPD and cryptosporidiosis led to impaired growth and weight gain. C. parvum-infected dPD mice showed increased serum MPO and serum amyloid A (SAA) levels, markers of systemic inflammation. dPD-infected mice showed greater MPO, NF-kB expression, and Iba-1 immunolabeling in the prefrontal cortex, an important brain region involved in executive function. Our findings suggest MPO as a potential biomarker for intestinal-brain axis dysfunction due to environmental enteropathy. (c) 2023 Sociedade Brasileira de Infectologia. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Automated summary

This study aims to identify new biomarkers related to gut-brain axis dysfunction in children suffering from malnutrition and infection, and provides new insights into potential intervention strategies. The research found that MPO, a neutrophil-related tissue factor released during enteropathy, could drive gut-derived brain inflammation. Using a mouse model, the study showed that undernourished mice infected with Cryptosporidium displayed higher levels of intestinal inflammation markers, systemic inflammation markers, and brain inflammation markers.