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A Gluten-Free Diet during Pregnancy and Early Life Increases Short Chain Fatty Acid-Producing Bacteria and Regulatory T Cells in Prediabetic NOD Mice

The incidence of the autoimmune disease type 1 diabetes is increasing, likely caused by environmental factors. A gluten-free diet has previously been shown to ameliorate autoimmune diabetes in non-obese diabetic (NOD) mice and humans. Although the exact mechanisms are not understood, interventions i...

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Autores principales: Johansen, Valdemar Brimnes Ingemann, Færø, Daisy, Buschard, Karsten, Kristiansen, Karsten, Pociot, Flemming, Kiilerich, Pia, Josefsen, Knud, Haupt-Jorgensen, Martin, Antvorskov, Julie Christine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10297205/
https://www.ncbi.nlm.nih.gov/pubmed/37371037
http://dx.doi.org/10.3390/cells12121567
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author Johansen, Valdemar Brimnes Ingemann
Færø, Daisy
Buschard, Karsten
Kristiansen, Karsten
Pociot, Flemming
Kiilerich, Pia
Josefsen, Knud
Haupt-Jorgensen, Martin
Antvorskov, Julie Christine
author_facet Johansen, Valdemar Brimnes Ingemann
Færø, Daisy
Buschard, Karsten
Kristiansen, Karsten
Pociot, Flemming
Kiilerich, Pia
Josefsen, Knud
Haupt-Jorgensen, Martin
Antvorskov, Julie Christine
author_sort Johansen, Valdemar Brimnes Ingemann
collection PubMed
description The incidence of the autoimmune disease type 1 diabetes is increasing, likely caused by environmental factors. A gluten-free diet has previously been shown to ameliorate autoimmune diabetes in non-obese diabetic (NOD) mice and humans. Although the exact mechanisms are not understood, interventions influencing the intestinal microbiota early in life affect the risk of type 1 diabetes. Here, we characterize how NOD mice that are fed a gluten-free (GF) diet differ from NOD mice that are fed a gluten-containing standard (STD) diet in terms of their microbiota composition by 16S rRNA gene amplicon sequencing and pancreatic immune environment by real-time quantitative PCR at the prediabetic stage at 6 and 13 weeks of age. Gut microbiota analysis revealed highly distinct microbiota compositions in both the cecum and the colon of GF-fed mice compared with STD-fed mice. The microbiotas of the GF-fed mice were characterized by an increased Firmicutes/Bacteroidetes ratio, an increased abundance of short chain fatty acid (particularly butyrate)-producing bacteria, and a reduced abundance of Lactobacilli compared with STD mice. We found that the insulitis score in the GF mice was significantly reduced compared with the STD mice and that the markers for regulatory T cells and T helper 2 cells were upregulated in the pancreas of the GF mice. In conclusion, a GF diet during pre- and early post-natal life induces shifts in the cecal and colonic microbiota compatible with a less inflammatory environment, providing a likely mechanism for the protective effect of a GF diet in humans.
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spelling pubmed-102972052023-06-28 A Gluten-Free Diet during Pregnancy and Early Life Increases Short Chain Fatty Acid-Producing Bacteria and Regulatory T Cells in Prediabetic NOD Mice Johansen, Valdemar Brimnes Ingemann Færø, Daisy Buschard, Karsten Kristiansen, Karsten Pociot, Flemming Kiilerich, Pia Josefsen, Knud Haupt-Jorgensen, Martin Antvorskov, Julie Christine Cells Article The incidence of the autoimmune disease type 1 diabetes is increasing, likely caused by environmental factors. A gluten-free diet has previously been shown to ameliorate autoimmune diabetes in non-obese diabetic (NOD) mice and humans. Although the exact mechanisms are not understood, interventions influencing the intestinal microbiota early in life affect the risk of type 1 diabetes. Here, we characterize how NOD mice that are fed a gluten-free (GF) diet differ from NOD mice that are fed a gluten-containing standard (STD) diet in terms of their microbiota composition by 16S rRNA gene amplicon sequencing and pancreatic immune environment by real-time quantitative PCR at the prediabetic stage at 6 and 13 weeks of age. Gut microbiota analysis revealed highly distinct microbiota compositions in both the cecum and the colon of GF-fed mice compared with STD-fed mice. The microbiotas of the GF-fed mice were characterized by an increased Firmicutes/Bacteroidetes ratio, an increased abundance of short chain fatty acid (particularly butyrate)-producing bacteria, and a reduced abundance of Lactobacilli compared with STD mice. We found that the insulitis score in the GF mice was significantly reduced compared with the STD mice and that the markers for regulatory T cells and T helper 2 cells were upregulated in the pancreas of the GF mice. In conclusion, a GF diet during pre- and early post-natal life induces shifts in the cecal and colonic microbiota compatible with a less inflammatory environment, providing a likely mechanism for the protective effect of a GF diet in humans. MDPI 2023-06-06 /pmc/articles/PMC10297205/ /pubmed/37371037 http://dx.doi.org/10.3390/cells12121567 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Johansen, Valdemar Brimnes Ingemann
Færø, Daisy
Buschard, Karsten
Kristiansen, Karsten
Pociot, Flemming
Kiilerich, Pia
Josefsen, Knud
Haupt-Jorgensen, Martin
Antvorskov, Julie Christine
A Gluten-Free Diet during Pregnancy and Early Life Increases Short Chain Fatty Acid-Producing Bacteria and Regulatory T Cells in Prediabetic NOD Mice
title A Gluten-Free Diet during Pregnancy and Early Life Increases Short Chain Fatty Acid-Producing Bacteria and Regulatory T Cells in Prediabetic NOD Mice
title_full A Gluten-Free Diet during Pregnancy and Early Life Increases Short Chain Fatty Acid-Producing Bacteria and Regulatory T Cells in Prediabetic NOD Mice
title_fullStr A Gluten-Free Diet during Pregnancy and Early Life Increases Short Chain Fatty Acid-Producing Bacteria and Regulatory T Cells in Prediabetic NOD Mice
title_full_unstemmed A Gluten-Free Diet during Pregnancy and Early Life Increases Short Chain Fatty Acid-Producing Bacteria and Regulatory T Cells in Prediabetic NOD Mice
title_short A Gluten-Free Diet during Pregnancy and Early Life Increases Short Chain Fatty Acid-Producing Bacteria and Regulatory T Cells in Prediabetic NOD Mice
title_sort gluten-free diet during pregnancy and early life increases short chain fatty acid-producing bacteria and regulatory t cells in prediabetic nod mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10297205/
https://www.ncbi.nlm.nih.gov/pubmed/37371037
http://dx.doi.org/10.3390/cells12121567
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