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Dietary Fiber as a Counterbalance to Age-Related Microglial Cell Dysfunction

With increasing age, microglia shift toward a pro-inflammatory phenotype that may predispose individuals to neurodegenerative disease. Because fiber fermentation in the colon produces bioactive short-chain fatty acids (SCFAs; e.g., acetate, butyrate, and propionate) that signal through the gut-brain...

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Autores principales: Vailati-Riboni, Mario, Rund, Laurie, Caetano-Silva, Maria Elisa, Hutchinson, Noah T., Wang, Selena S., Soto-Díaz, Katiria, Woods, Jeffrey A., Steelman, Andrew J., Johnson, Rodney W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964049/
https://www.ncbi.nlm.nih.gov/pubmed/35360677
http://dx.doi.org/10.3389/fnut.2022.835824
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author Vailati-Riboni, Mario
Rund, Laurie
Caetano-Silva, Maria Elisa
Hutchinson, Noah T.
Wang, Selena S.
Soto-Díaz, Katiria
Woods, Jeffrey A.
Steelman, Andrew J.
Johnson, Rodney W.
author_facet Vailati-Riboni, Mario
Rund, Laurie
Caetano-Silva, Maria Elisa
Hutchinson, Noah T.
Wang, Selena S.
Soto-Díaz, Katiria
Woods, Jeffrey A.
Steelman, Andrew J.
Johnson, Rodney W.
author_sort Vailati-Riboni, Mario
collection PubMed
description With increasing age, microglia shift toward a pro-inflammatory phenotype that may predispose individuals to neurodegenerative disease. Because fiber fermentation in the colon produces bioactive short-chain fatty acids (SCFAs; e.g., acetate, butyrate, and propionate) that signal through the gut-brain axis, increasing dietary fiber may prevent or reverse age-related dysregulation of microglia. Adult (3–4 months old) and aged (23–24 months old) male and female mice were given ad libitum access to a modified AIN-93M diet with 1% cellulose or the same diet with 2.5 or 5.0% inulin for 8 weeks. Several adult and aged male mice fed 0 or 5% inulin were randomly selected for whole brain single-cell RNA sequencing (scRNA-seq) and differential gene expression analysis to classify brain microglia according to gene expression profile; and identify additional genetic markers of aging as possible targets for dietary interventions. Microglia were isolated from remaining mice and expression of selected aging-, inflammatory-, and sensome-related genes was assessed by Fluidigm as was the ex vivo secretion of tumor necrosis factor-alpha (TNF-α). SCFAs were measured in samples collected from the cecum. Microglia from adult and aged mice segregated into distinct phenotypes according to their gene expression profile. In aged mice, a considerably greater proportion of the population of microglia was identified being “activated” and a considerably smaller proportion was identified being “quiescent.” These findings using whole brain scRNA-seq were largely corroborated using highly purified microglia and Fluidigm analysis to assess a selected panel of genes. Aged mice compared to adults had lower levels of SCFA’s in cecum. Dietary inulin increased SCFAs in cecum and mostly restored microglial cell gene expression and TNF-α secretion to that seen in adults. Sex differences were observed with females having lower levels of SCFAs in cecum and increased neuroinflammation. Overall, these data support the use of fiber supplementation as a strategy to counterbalance the age-related microglial dysregulation.
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spelling pubmed-89640492022-03-30 Dietary Fiber as a Counterbalance to Age-Related Microglial Cell Dysfunction Vailati-Riboni, Mario Rund, Laurie Caetano-Silva, Maria Elisa Hutchinson, Noah T. Wang, Selena S. Soto-Díaz, Katiria Woods, Jeffrey A. Steelman, Andrew J. Johnson, Rodney W. Front Nutr Nutrition With increasing age, microglia shift toward a pro-inflammatory phenotype that may predispose individuals to neurodegenerative disease. Because fiber fermentation in the colon produces bioactive short-chain fatty acids (SCFAs; e.g., acetate, butyrate, and propionate) that signal through the gut-brain axis, increasing dietary fiber may prevent or reverse age-related dysregulation of microglia. Adult (3–4 months old) and aged (23–24 months old) male and female mice were given ad libitum access to a modified AIN-93M diet with 1% cellulose or the same diet with 2.5 or 5.0% inulin for 8 weeks. Several adult and aged male mice fed 0 or 5% inulin were randomly selected for whole brain single-cell RNA sequencing (scRNA-seq) and differential gene expression analysis to classify brain microglia according to gene expression profile; and identify additional genetic markers of aging as possible targets for dietary interventions. Microglia were isolated from remaining mice and expression of selected aging-, inflammatory-, and sensome-related genes was assessed by Fluidigm as was the ex vivo secretion of tumor necrosis factor-alpha (TNF-α). SCFAs were measured in samples collected from the cecum. Microglia from adult and aged mice segregated into distinct phenotypes according to their gene expression profile. In aged mice, a considerably greater proportion of the population of microglia was identified being “activated” and a considerably smaller proportion was identified being “quiescent.” These findings using whole brain scRNA-seq were largely corroborated using highly purified microglia and Fluidigm analysis to assess a selected panel of genes. Aged mice compared to adults had lower levels of SCFA’s in cecum. Dietary inulin increased SCFAs in cecum and mostly restored microglial cell gene expression and TNF-α secretion to that seen in adults. Sex differences were observed with females having lower levels of SCFAs in cecum and increased neuroinflammation. Overall, these data support the use of fiber supplementation as a strategy to counterbalance the age-related microglial dysregulation. Frontiers Media S.A. 2022-03-14 /pmc/articles/PMC8964049/ /pubmed/35360677 http://dx.doi.org/10.3389/fnut.2022.835824 Text en Copyright © 2022 Vailati-Riboni, Rund, Caetano-Silva, Hutchinson, Wang, Soto-Díaz, Woods, Steelman and Johnson. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Nutrition
Vailati-Riboni, Mario
Rund, Laurie
Caetano-Silva, Maria Elisa
Hutchinson, Noah T.
Wang, Selena S.
Soto-Díaz, Katiria
Woods, Jeffrey A.
Steelman, Andrew J.
Johnson, Rodney W.
Dietary Fiber as a Counterbalance to Age-Related Microglial Cell Dysfunction
title Dietary Fiber as a Counterbalance to Age-Related Microglial Cell Dysfunction
title_full Dietary Fiber as a Counterbalance to Age-Related Microglial Cell Dysfunction
title_fullStr Dietary Fiber as a Counterbalance to Age-Related Microglial Cell Dysfunction
title_full_unstemmed Dietary Fiber as a Counterbalance to Age-Related Microglial Cell Dysfunction
title_short Dietary Fiber as a Counterbalance to Age-Related Microglial Cell Dysfunction
title_sort dietary fiber as a counterbalance to age-related microglial cell dysfunction
topic Nutrition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8964049/
https://www.ncbi.nlm.nih.gov/pubmed/35360677
http://dx.doi.org/10.3389/fnut.2022.835824
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