Protein Malnutrition Modifies Innate Immunity and Gene Expression by Intestinal Epithelial Cells and Human Rotavirus Infection in Neonatal Gnotobiotic Pigs

ABSTRACT Malnutrition affects millions of children in developing countries, compromising immunity and contributing to increased rates of death from infectious diseases. Rotavirus is a major etiological agent of childhood diarrhea in developing countries, where malnutrition is prevalent. However, the...

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Autores principales:	Anastasia N. Vlasova, Francine C. Paim, Sukumar Kandasamy, Moyasar A. Alhamo, David D. Fischer, Stephanie N. Langel, Loic Deblais, Anand Kumar, Juliet Chepngeno, Lulu Shao, Huang-Chi Huang, Rosario A. Candelero-Rueda, Gireesh Rajashekara, Linda J. Saif
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	intestinal epithelial cells gnotobiotic piglets human infant fecal microbiota human rotavirus innate immunity intestinal epithelial barrier Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9291c5cc56e846e5b040c39e7bff2034
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spelling	oai:doaj.org-article:9291c5cc56e846e5b040c39e7bff20342021-11-15T15:21:45ZProtein Malnutrition Modifies Innate Immunity and Gene Expression by Intestinal Epithelial Cells and Human Rotavirus Infection in Neonatal Gnotobiotic Pigs10.1128/mSphere.00046-172379-5042https://doaj.org/article/9291c5cc56e846e5b040c39e7bff20342017-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00046-17https://doaj.org/toc/2379-5042ABSTRACT Malnutrition affects millions of children in developing countries, compromising immunity and contributing to increased rates of death from infectious diseases. Rotavirus is a major etiological agent of childhood diarrhea in developing countries, where malnutrition is prevalent. However, the interactions between the two and their combined effects on immune and intestinal functions are poorly understood. In this study, we used neonatal gnotobiotic (Gn) pigs transplanted with the fecal microbiota of a healthy 2-month-old infant (HIFM) and fed protein-deficient or -sufficient bovine milk diets. Protein deficiency induced hypoproteinemia, hypoalbuminemia, hypoglycemia, stunting, and generalized edema in Gn pigs, as observed in protein-malnourished children. Irrespective of the diet, human rotavirus (HRV) infection early, at HIFM posttransplantation day 3 (PTD3), resulted in adverse health effects and higher mortality rates (45 to 75%) than later HRV infection (PTD10). Protein malnutrition exacerbated HRV infection and affected the morphology and function of the small intestinal epithelial barrier. In pigs infected with HRV at PTD10, there was a uniform decrease in the function and/or frequencies of natural killer cells, plasmacytoid dendritic cells, and CD103+ and apoptotic mononuclear cells and altered gene expression profiles of intestinal epithelial cells (chromogranin A, mucin 2, proliferating cell nuclear antigen, SRY-Box 9, and villin). Thus, we have established the first HIFM-transplanted neonatal pig model that recapitulates major aspects of protein malnutrition in children and can be used to evaluate physiologically relevant interventions. Our findings provide an explanation of why nutrient-rich diets alone may lack efficacy in malnourished children. IMPORTANCE Malnutrition and rotavirus infection, prevalent in developing countries, individually and in combination, affect the health of millions of children, compromising their immunity and increasing the rates of death from infectious diseases. However, the interactions between the two and their combined effects on immune and intestinal functions are poorly understood. We have established the first human infant microbiota-transplanted neonatal pig model of childhood malnutrition that reproduced the impaired immune, intestinal, and other physiological functions seen in malnourished children. This model can be used to evaluate relevant dietary and other health-promoting interventions. Our findings provide an explanation of why adequate nutrition alone may lack efficacy in malnourished children.Anastasia N. VlasovaFrancine C. PaimSukumar KandasamyMoyasar A. AlhamoDavid D. FischerStephanie N. LangelLoic DeblaisAnand KumarJuliet ChepngenoLulu ShaoHuang-Chi HuangRosario A. Candelero-RuedaGireesh RajashekaraLinda J. SaifAmerican Society for Microbiologyarticleintestinal epithelial cellsgnotobiotic pigletshuman infant fecal microbiotahuman rotavirusinnate immunityintestinal epithelial barrierMicrobiologyQR1-502ENmSphere, Vol 2, Iss 2 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	intestinal epithelial cells gnotobiotic piglets human infant fecal microbiota human rotavirus innate immunity intestinal epithelial barrier Microbiology QR1-502
spellingShingle	intestinal epithelial cells gnotobiotic piglets human infant fecal microbiota human rotavirus innate immunity intestinal epithelial barrier Microbiology QR1-502 Anastasia N. Vlasova Francine C. Paim Sukumar Kandasamy Moyasar A. Alhamo David D. Fischer Stephanie N. Langel Loic Deblais Anand Kumar Juliet Chepngeno Lulu Shao Huang-Chi Huang Rosario A. Candelero-Rueda Gireesh Rajashekara Linda J. Saif Protein Malnutrition Modifies Innate Immunity and Gene Expression by Intestinal Epithelial Cells and Human Rotavirus Infection in Neonatal Gnotobiotic Pigs
description	ABSTRACT Malnutrition affects millions of children in developing countries, compromising immunity and contributing to increased rates of death from infectious diseases. Rotavirus is a major etiological agent of childhood diarrhea in developing countries, where malnutrition is prevalent. However, the interactions between the two and their combined effects on immune and intestinal functions are poorly understood. In this study, we used neonatal gnotobiotic (Gn) pigs transplanted with the fecal microbiota of a healthy 2-month-old infant (HIFM) and fed protein-deficient or -sufficient bovine milk diets. Protein deficiency induced hypoproteinemia, hypoalbuminemia, hypoglycemia, stunting, and generalized edema in Gn pigs, as observed in protein-malnourished children. Irrespective of the diet, human rotavirus (HRV) infection early, at HIFM posttransplantation day 3 (PTD3), resulted in adverse health effects and higher mortality rates (45 to 75%) than later HRV infection (PTD10). Protein malnutrition exacerbated HRV infection and affected the morphology and function of the small intestinal epithelial barrier. In pigs infected with HRV at PTD10, there was a uniform decrease in the function and/or frequencies of natural killer cells, plasmacytoid dendritic cells, and CD103+ and apoptotic mononuclear cells and altered gene expression profiles of intestinal epithelial cells (chromogranin A, mucin 2, proliferating cell nuclear antigen, SRY-Box 9, and villin). Thus, we have established the first HIFM-transplanted neonatal pig model that recapitulates major aspects of protein malnutrition in children and can be used to evaluate physiologically relevant interventions. Our findings provide an explanation of why nutrient-rich diets alone may lack efficacy in malnourished children. IMPORTANCE Malnutrition and rotavirus infection, prevalent in developing countries, individually and in combination, affect the health of millions of children, compromising their immunity and increasing the rates of death from infectious diseases. However, the interactions between the two and their combined effects on immune and intestinal functions are poorly understood. We have established the first human infant microbiota-transplanted neonatal pig model of childhood malnutrition that reproduced the impaired immune, intestinal, and other physiological functions seen in malnourished children. This model can be used to evaluate relevant dietary and other health-promoting interventions. Our findings provide an explanation of why adequate nutrition alone may lack efficacy in malnourished children.
format	article
author	Anastasia N. Vlasova Francine C. Paim Sukumar Kandasamy Moyasar A. Alhamo David D. Fischer Stephanie N. Langel Loic Deblais Anand Kumar Juliet Chepngeno Lulu Shao Huang-Chi Huang Rosario A. Candelero-Rueda Gireesh Rajashekara Linda J. Saif
author_facet	Anastasia N. Vlasova Francine C. Paim Sukumar Kandasamy Moyasar A. Alhamo David D. Fischer Stephanie N. Langel Loic Deblais Anand Kumar Juliet Chepngeno Lulu Shao Huang-Chi Huang Rosario A. Candelero-Rueda Gireesh Rajashekara Linda J. Saif
author_sort	Anastasia N. Vlasova
title	Protein Malnutrition Modifies Innate Immunity and Gene Expression by Intestinal Epithelial Cells and Human Rotavirus Infection in Neonatal Gnotobiotic Pigs
title_short	Protein Malnutrition Modifies Innate Immunity and Gene Expression by Intestinal Epithelial Cells and Human Rotavirus Infection in Neonatal Gnotobiotic Pigs
title_full	Protein Malnutrition Modifies Innate Immunity and Gene Expression by Intestinal Epithelial Cells and Human Rotavirus Infection in Neonatal Gnotobiotic Pigs
title_fullStr	Protein Malnutrition Modifies Innate Immunity and Gene Expression by Intestinal Epithelial Cells and Human Rotavirus Infection in Neonatal Gnotobiotic Pigs
title_full_unstemmed	Protein Malnutrition Modifies Innate Immunity and Gene Expression by Intestinal Epithelial Cells and Human Rotavirus Infection in Neonatal Gnotobiotic Pigs
title_sort	protein malnutrition modifies innate immunity and gene expression by intestinal epithelial cells and human rotavirus infection in neonatal gnotobiotic pigs
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/9291c5cc56e846e5b040c39e7bff2034
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_version_	1718428144852008960

Protein Malnutrition Modifies Innate Immunity and Gene Expression by Intestinal Epithelial Cells and Human Rotavirus Infection in Neonatal Gnotobiotic Pigs

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