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

• Published in: The Brazilian journal of infectious diseases Vol. 27; no. 3; p. 102776
• Main Authors: Oriá, Reinaldo B., Costa, Deiziane V.S., de Medeiros, Pedro Henrique Q.S., Roque, Cássia R., Dias, Ronaldo P., Warren, Cirle A., Bolick, David T., Guerrant, Richard L.
• Format: Journal Article
• Language: English; Portuguese
• Published: Brazil Elsevier España, S.L.U 01.05.2023; Contexto; Elsevier; Brazilian Society of Infectious Diseases
• Subjects: Analysis; Animals; Biological markers; Brain - pathology; Complications and side effects; Cryptosporidiosis; Cryptosporidiosis - complications; Cryptosporidiosis - pathology; Cryptosporidium; Cryptosporidium parvum; Diagnosis; Enzyme-linked immunosorbent assay; Feces; Gut; INFECTIOUS DISEASES; Inflammation; Malnutrition; Malnutrition - pathology; Mice; Mice, Inbred C57BL; Myeloperoxidase; Neuroinflammation; NF-kappa B; Original; Peroxidase; Serum Amyloid A Protein; Brazil; Neuroinflammation; Myeloperoxidase; Cryptosporidium parvum; Malnutrition; Gut
• ISSN: 1413-8670; 1678-4391; 1678-4391
• DOI: 10.1016/j.bjid.2023.102776

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 identify new biomarkers that may be related to gut-brain axis dysfunction in children suffering from the malnutrition/infection vicious cycle, necessary for better intervention strategies. Myeloperoxidase (MPO) is a well-known neutrophil-related tissue factor released during enteropathy 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 immunostaining. 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.