Cargando…

Vitamin B12 coordinates ileal epithelial cell and microbiota functions to resist Salmonella infection in mice

Deprivation of vitamin B12 (VB12) is linked to various diseases, but the underlying mechanisms in disease progression are poorly understood. Using multiomic approaches, we elucidated the responses of ileal epithelial cells (iECs) and gut microbiome to VB12 dietary restriction. Here, VB12 deficiency...

Descripción completa

Detalles Bibliográficos
Autores principales: Ge, Yong, Zadeh, Mojgan, Mohamadzadeh, Mansour
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9184849/
https://www.ncbi.nlm.nih.gov/pubmed/35674742
http://dx.doi.org/10.1084/jem.20220057
_version_ 1784724619942428672
author Ge, Yong
Zadeh, Mojgan
Mohamadzadeh, Mansour
author_facet Ge, Yong
Zadeh, Mojgan
Mohamadzadeh, Mansour
author_sort Ge, Yong
collection PubMed
description Deprivation of vitamin B12 (VB12) is linked to various diseases, but the underlying mechanisms in disease progression are poorly understood. Using multiomic approaches, we elucidated the responses of ileal epithelial cells (iECs) and gut microbiome to VB12 dietary restriction. Here, VB12 deficiency impaired the transcriptional and metabolic programming of iECs and reduced epithelial mitochondrial respiration and carnitine shuttling during intestinal Salmonella Typhimurium (STm) infection. Fecal microbial and untargeted metabolomic profiling identified marked changes related to VB12 deficiency, including reductions of metabolites potentially activating mitochondrial β-oxidation in iECs and short-chain fatty acids (SCFAs). Depletion of SCFA-producing microbes by streptomycin treatment decreased the VB12-dependent STm protection. Moreover, compromised mitochondrial function of iECs correlated with declined cell capability to utilize oxygen, leading to uncontrolled oxygen-dependent STm expansion in VB12-deficient mice. Our findings uncovered previously unrecognized mechanisms through which VB12 coordinates ileal epithelial mitochondrial homeostasis and gut microbiota to regulate epithelial oxygenation, resulting in the control of aerobic STm infection.
format Online
Article
Text
id pubmed-9184849
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-91848492022-12-08 Vitamin B12 coordinates ileal epithelial cell and microbiota functions to resist Salmonella infection in mice Ge, Yong Zadeh, Mojgan Mohamadzadeh, Mansour J Exp Med Article Deprivation of vitamin B12 (VB12) is linked to various diseases, but the underlying mechanisms in disease progression are poorly understood. Using multiomic approaches, we elucidated the responses of ileal epithelial cells (iECs) and gut microbiome to VB12 dietary restriction. Here, VB12 deficiency impaired the transcriptional and metabolic programming of iECs and reduced epithelial mitochondrial respiration and carnitine shuttling during intestinal Salmonella Typhimurium (STm) infection. Fecal microbial and untargeted metabolomic profiling identified marked changes related to VB12 deficiency, including reductions of metabolites potentially activating mitochondrial β-oxidation in iECs and short-chain fatty acids (SCFAs). Depletion of SCFA-producing microbes by streptomycin treatment decreased the VB12-dependent STm protection. Moreover, compromised mitochondrial function of iECs correlated with declined cell capability to utilize oxygen, leading to uncontrolled oxygen-dependent STm expansion in VB12-deficient mice. Our findings uncovered previously unrecognized mechanisms through which VB12 coordinates ileal epithelial mitochondrial homeostasis and gut microbiota to regulate epithelial oxygenation, resulting in the control of aerobic STm infection. Rockefeller University Press 2022-06-08 /pmc/articles/PMC9184849/ /pubmed/35674742 http://dx.doi.org/10.1084/jem.20220057 Text en © 2022 Ge et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Ge, Yong
Zadeh, Mojgan
Mohamadzadeh, Mansour
Vitamin B12 coordinates ileal epithelial cell and microbiota functions to resist Salmonella infection in mice
title Vitamin B12 coordinates ileal epithelial cell and microbiota functions to resist Salmonella infection in mice
title_full Vitamin B12 coordinates ileal epithelial cell and microbiota functions to resist Salmonella infection in mice
title_fullStr Vitamin B12 coordinates ileal epithelial cell and microbiota functions to resist Salmonella infection in mice
title_full_unstemmed Vitamin B12 coordinates ileal epithelial cell and microbiota functions to resist Salmonella infection in mice
title_short Vitamin B12 coordinates ileal epithelial cell and microbiota functions to resist Salmonella infection in mice
title_sort vitamin b12 coordinates ileal epithelial cell and microbiota functions to resist salmonella infection in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9184849/
https://www.ncbi.nlm.nih.gov/pubmed/35674742
http://dx.doi.org/10.1084/jem.20220057
work_keys_str_mv AT geyong vitaminb12coordinatesilealepithelialcellandmicrobiotafunctionstoresistsalmonellainfectioninmice
AT zadehmojgan vitaminb12coordinatesilealepithelialcellandmicrobiotafunctionstoresistsalmonellainfectioninmice
AT mohamadzadehmansour vitaminb12coordinatesilealepithelialcellandmicrobiotafunctionstoresistsalmonellainfectioninmice