A Murine Model of Maternal Micronutrient Deficiencies and Gut Inflammatory Host-microbe Interactions in the Offspring.

Autor:	Holani R; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada; Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada., Littlejohn PT; Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada; Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada; Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada., Edwards K; British Columbia Children's Hospital Research Institute, Vancouver, British Columbia, Canada., Petersen C; Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada; British Columbia Children's Hospital, Vancouver, British Columbia, Canada., Moon KM; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada; Biochemistry and Molecular Biology Department, University of British Columbia, Vancouver, British Columbia, Canada., Stacey RG; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada., Bozorgmehr T; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada; Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada., Gerbec ZJ; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada; Biochemistry and Molecular Biology Department, University of British Columbia, Vancouver, British Columbia, Canada; Department of Integrative Oncology, BC Cancer Research Institute, Vancouver, British Columbia, Canada., Serapio-Palacios A; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada; Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada., Krekhno Z; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada; Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada., Donald K; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada; Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada., Foster LJ; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada; Biochemistry and Molecular Biology Department, University of British Columbia, Vancouver, British Columbia, Canada., Turvey SE; Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada., Finlay BB; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada; Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada; Biochemistry and Molecular Biology Department, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: bfinlay@interchange.ubc.ca.
Jazyk:	angličtina
Zdroj:	Cellular and molecular gastroenterology and hepatology [Cell Mol Gastroenterol Hepatol] 2024; Vol. 17 (5), pp. 827-852. Date of Electronic Publication: 2024 Feb 01.
DOI:	10.1016/j.jcmgh.2024.01.018
Abstrakt:	Background & Aims: Micronutrient deficiency (MND) (ie, lack of vitamins and minerals) during pregnancy is a major public health concern. Historically, studies have considered micronutrients in isolation; however, MNDs rarely occur alone. The impact of co-occurring MNDs on public health, mainly in shaping mucosal colonization by pathobionts from the Enterobacteriaceae family, remains undetermined due to lack of relevant animal models. Methods: To establish a maternal murine model of multiple MND (MMND), we customized a diet deficient in vitamins (A, B12, and B9) and minerals (iron and zinc) that most commonly affect children and women of reproductive age. Thereafter, mucosal adherence by Enterobacteriaceae, the associated inflammatory markers, and proteomic profile of intestines were determined in the offspring of MMND mothers (hereafter, low micronutrient [LM] pups) via bacterial plating, flow cytometry, and mass spectrometry, respectively. For human validation, Enterobacteriaceae abundance, assessed via 16s sequencing of 3-month-old infant fecal samples (n = 100), was correlated with micronutrient metabolites using Spearman's correlation in meconium of children from the CHILD birth cohort. Results: We developed an MMND model and reported an increase in colonic abundance of Enterobacteriaceae in LM pups at weaning. Findings from CHILD cohort confirmed a negative correlation between Enterobacteriaceae and micronutrient availability. Furthermore, pro-inflammatory cytokines and increased infiltration of lymphocyte antigen 6 complex high monocytes and M1-like macrophages were evident in the colons of LM pups. Mechanistically, mitochondrial dysfunction marked by reduced expression of nicotinamide adenine dinucleotide (NAD)H dehydrogenase and increased expression of NAD phosphate oxidase (Nox) 1 contributed to the Enterobacteriaceae bloom. Conclusion: This study establishes an early life MMND link to intestinal pathobiont colonization and mucosal inflammation via damaged mitochondria in the offspring. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu