Clostridial Butyrate Biosynthesis Enzymes Are Significantly Depleted in the Gut Microbiota of Nonobese Diabetic Mice

ABSTRACT Increasing evidence suggests that the intestinal microbiota is involved in the pathogenesis of type 1 diabetes (T1D). Here we sought to determine which gut microbial taxa and functions vary between nonobese diabetic (NOD) mice and genetically modified NOD mice protected from T1D (Eα16/NOD)...

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Autores principales:	Alessandro Tanca, Antonio Palomba, Cristina Fraumene, Valeria Manghina, Michael Silverman, Sergio Uzzau
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	butyrate diabetes metaproteomics microbiome short-chain fatty acids Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4bc749e457524cc1bdf58d159f7665eb
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spelling	oai:doaj.org-article:4bc749e457524cc1bdf58d159f7665eb2021-11-15T15:22:26ZClostridial Butyrate Biosynthesis Enzymes Are Significantly Depleted in the Gut Microbiota of Nonobese Diabetic Mice10.1128/mSphere.00492-182379-5042https://doaj.org/article/4bc749e457524cc1bdf58d159f7665eb2018-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00492-18https://doaj.org/toc/2379-5042ABSTRACT Increasing evidence suggests that the intestinal microbiota is involved in the pathogenesis of type 1 diabetes (T1D). Here we sought to determine which gut microbial taxa and functions vary between nonobese diabetic (NOD) mice and genetically modified NOD mice protected from T1D (Eα16/NOD) at 10 weeks of age in the time window between insulitis development and T1D onset. The gut microbiota of NOD mice were investigated by analyzing stool samples with a metaproteogenomic approach, comprising both 16S rRNA gene sequencing and microbial proteome profiling through high-resolution mass spectrometry. A depletion of Firmicutes (particularly, several members of Lachnospiraceae) in the NOD gut microbiota was observed compared to the level in the Eα16/NOD mice microbiota. Moreover, the analysis of proteins actively produced by the gut microbiota revealed different profiles between NOD and Eα16/NOD mice, with the production of butyrate biosynthesis enzymes being significantly reduced in diabetic mice. Our results support a model for gut microbiota influence on T1D development involving bacterium-produced metabolites as butyrate. IMPORTANCE Alterations of the gut microbiota early in age have been hypothesized to impact T1D autoimmune pathogenesis. In the NOD mouse model, protection from T1D has been found to operate via modulation of the composition of the intestinal microbiota during a critical early window of ontogeny, although little is known about microbiota functions related to T1D development. Here, we show which gut microbial functions are specifically associated with protection from T1D in the time window between insulitis development and T1D onset. In particular, we describe that production of butyrate biosynthesis enzymes is significantly reduced in NOD mice, supporting the hypothesis that modulating the gut microbiota butyrate production may influence T1D development.Alessandro TancaAntonio PalombaCristina FraumeneValeria ManghinaMichael SilvermanSergio UzzauAmerican Society for Microbiologyarticlebutyratediabetesmetaproteomicsmicrobiomeshort-chain fatty acidsMicrobiologyQR1-502ENmSphere, Vol 3, Iss 5 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	butyrate diabetes metaproteomics microbiome short-chain fatty acids Microbiology QR1-502
spellingShingle	butyrate diabetes metaproteomics microbiome short-chain fatty acids Microbiology QR1-502 Alessandro Tanca Antonio Palomba Cristina Fraumene Valeria Manghina Michael Silverman Sergio Uzzau Clostridial Butyrate Biosynthesis Enzymes Are Significantly Depleted in the Gut Microbiota of Nonobese Diabetic Mice
description	ABSTRACT Increasing evidence suggests that the intestinal microbiota is involved in the pathogenesis of type 1 diabetes (T1D). Here we sought to determine which gut microbial taxa and functions vary between nonobese diabetic (NOD) mice and genetically modified NOD mice protected from T1D (Eα16/NOD) at 10 weeks of age in the time window between insulitis development and T1D onset. The gut microbiota of NOD mice were investigated by analyzing stool samples with a metaproteogenomic approach, comprising both 16S rRNA gene sequencing and microbial proteome profiling through high-resolution mass spectrometry. A depletion of Firmicutes (particularly, several members of Lachnospiraceae) in the NOD gut microbiota was observed compared to the level in the Eα16/NOD mice microbiota. Moreover, the analysis of proteins actively produced by the gut microbiota revealed different profiles between NOD and Eα16/NOD mice, with the production of butyrate biosynthesis enzymes being significantly reduced in diabetic mice. Our results support a model for gut microbiota influence on T1D development involving bacterium-produced metabolites as butyrate. IMPORTANCE Alterations of the gut microbiota early in age have been hypothesized to impact T1D autoimmune pathogenesis. In the NOD mouse model, protection from T1D has been found to operate via modulation of the composition of the intestinal microbiota during a critical early window of ontogeny, although little is known about microbiota functions related to T1D development. Here, we show which gut microbial functions are specifically associated with protection from T1D in the time window between insulitis development and T1D onset. In particular, we describe that production of butyrate biosynthesis enzymes is significantly reduced in NOD mice, supporting the hypothesis that modulating the gut microbiota butyrate production may influence T1D development.
format	article
author	Alessandro Tanca Antonio Palomba Cristina Fraumene Valeria Manghina Michael Silverman Sergio Uzzau
author_facet	Alessandro Tanca Antonio Palomba Cristina Fraumene Valeria Manghina Michael Silverman Sergio Uzzau
author_sort	Alessandro Tanca
title	Clostridial Butyrate Biosynthesis Enzymes Are Significantly Depleted in the Gut Microbiota of Nonobese Diabetic Mice
title_short	Clostridial Butyrate Biosynthesis Enzymes Are Significantly Depleted in the Gut Microbiota of Nonobese Diabetic Mice
title_full	Clostridial Butyrate Biosynthesis Enzymes Are Significantly Depleted in the Gut Microbiota of Nonobese Diabetic Mice
title_fullStr	Clostridial Butyrate Biosynthesis Enzymes Are Significantly Depleted in the Gut Microbiota of Nonobese Diabetic Mice
title_full_unstemmed	Clostridial Butyrate Biosynthesis Enzymes Are Significantly Depleted in the Gut Microbiota of Nonobese Diabetic Mice
title_sort	clostridial butyrate biosynthesis enzymes are significantly depleted in the gut microbiota of nonobese diabetic mice
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/4bc749e457524cc1bdf58d159f7665eb
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Clostridial Butyrate Biosynthesis Enzymes Are Significantly Depleted in the Gut Microbiota of Nonobese Diabetic Mice

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