Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac Disease
The composition of the gut microbiome reflects the overall health status of the host. In this study, stool samples representing the gut microbiomes from 6 gluten-sensitive (GS) captive juvenile rhesus macaques were compared with those from 6 healthy, age- and diet-matched peers. A total of 48 sample...
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doaj-90133130ebab4df589afa4f39dd4f5132020-11-24T21:43:25ZengMDPI AGNutrients2072-66432016-10-0181168410.3390/nu8110684nu8110684Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac DiseaseMahesh Mohan0Cheryl-Emiliane T. Chow1Caitlin N. Ryan2Luisa S. Chan3Jason Dufour4Pyone P. Aye5James Blanchard6Charles P. Moehs7Karol Sestak8Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USASecond Genome Inc., San Francisco, CA 94080, USASecond Genome Inc., San Francisco, CA 94080, USASecond Genome Inc., San Francisco, CA 94080, USADivision of Veterinary Resources, Tulane National Primate Research Center, Covington, LA 70433, USADivision of Comparative Pathology, Tulane National Primate Research Center, Covington, LA 70433, USADivision of Veterinary Resources, Tulane National Primate Research Center, Covington, LA 70433, USAArcadia Biosciences Inc., Seattle, WA 98119, USADivision of Microbiology, Tulane National Primate Research Center, Covington, LA 70433, USAThe composition of the gut microbiome reflects the overall health status of the host. In this study, stool samples representing the gut microbiomes from 6 gluten-sensitive (GS) captive juvenile rhesus macaques were compared with those from 6 healthy, age- and diet-matched peers. A total of 48 samples representing both groups were studied using V4 16S rRNA gene DNA analysis. Samples from GS macaques were further characterized based on type of diet administered: conventional monkey chow, i.e., wheat gluten-containing diet (GD), gluten-free diet (GFD), barley gluten-derived diet (BOMI) and reduced gluten barley-derived diet (RGB). It was hypothesized that the GD diet would lower the gut microbial diversity in GS macaques. This is the first report illustrating the reduction of gut microbial alpha-diversity (p < 0.05) following the consumption of dietary gluten in GS macaques. Selected bacterial families (e.g., Streptococcaceae and Lactobacillaceae) were enriched in GS macaques while Coriobacteriaceae was enriched in healthy animals. Within several weeks after the replacement of the GD by the GFD diet, the composition (beta-diversity) of gut microbiome in GS macaques started to change (p = 0.011) towards that of a normal macaque. Significance for alpha-diversity however, was not reached by the day 70 when the feeding experiment ended. Several inflammation-associated microRNAs (miR-203, -204, -23a, -23b and -29b) were upregulated (p < 0.05) in jejunum of 4 biopsied GS macaques fed GD with predicted binding sites on 16S ribosomal RNA of Lactobacillus reuteri (accession number: NR_025911), Prevotella stercorea (NR_041364) and Streptococcus luteciae (AJ297218) that were overrepresented in feces. Additionally, claudin-1, a validated tight junction protein target of miR-29b was significantly downregulated in jejunal epithelium of GS macaques. Taken together, we predict that with the introduction of effective treatments in future studies the diversity of gut microbiomes in GS macaques will approach those of healthy individuals. Further studies are needed to elucidate the regulatory pathways of inflammatory miRNAs in intestinal mucosa of GS macaques and to correlate their expression with gut dysbiosis.http://www.mdpi.com/2072-6643/8/11/684celiacglutengutmicrobiomemicrobiotadysbiosisrhesusmacaquemetagenomics16S rRNAmiRNAchronic inflammation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Mahesh Mohan Cheryl-Emiliane T. Chow Caitlin N. Ryan Luisa S. Chan Jason Dufour Pyone P. Aye James Blanchard Charles P. Moehs Karol Sestak |
spellingShingle |
Mahesh Mohan Cheryl-Emiliane T. Chow Caitlin N. Ryan Luisa S. Chan Jason Dufour Pyone P. Aye James Blanchard Charles P. Moehs Karol Sestak Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac Disease Nutrients celiac gluten gut microbiome microbiota dysbiosis rhesus macaque metagenomics 16S rRNA miRNA chronic inflammation |
author_facet |
Mahesh Mohan Cheryl-Emiliane T. Chow Caitlin N. Ryan Luisa S. Chan Jason Dufour Pyone P. Aye James Blanchard Charles P. Moehs Karol Sestak |
author_sort |
Mahesh Mohan |
title |
Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac Disease |
title_short |
Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac Disease |
title_full |
Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac Disease |
title_fullStr |
Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac Disease |
title_full_unstemmed |
Dietary Gluten-Induced Gut Dysbiosis Is Accompanied by Selective Upregulation of microRNAs with Intestinal Tight Junction and Bacteria-Binding Motifs in Rhesus Macaque Model of Celiac Disease |
title_sort |
dietary gluten-induced gut dysbiosis is accompanied by selective upregulation of micrornas with intestinal tight junction and bacteria-binding motifs in rhesus macaque model of celiac disease |
publisher |
MDPI AG |
series |
Nutrients |
issn |
2072-6643 |
publishDate |
2016-10-01 |
description |
The composition of the gut microbiome reflects the overall health status of the host. In this study, stool samples representing the gut microbiomes from 6 gluten-sensitive (GS) captive juvenile rhesus macaques were compared with those from 6 healthy, age- and diet-matched peers. A total of 48 samples representing both groups were studied using V4 16S rRNA gene DNA analysis. Samples from GS macaques were further characterized based on type of diet administered: conventional monkey chow, i.e., wheat gluten-containing diet (GD), gluten-free diet (GFD), barley gluten-derived diet (BOMI) and reduced gluten barley-derived diet (RGB). It was hypothesized that the GD diet would lower the gut microbial diversity in GS macaques. This is the first report illustrating the reduction of gut microbial alpha-diversity (p < 0.05) following the consumption of dietary gluten in GS macaques. Selected bacterial families (e.g., Streptococcaceae and Lactobacillaceae) were enriched in GS macaques while Coriobacteriaceae was enriched in healthy animals. Within several weeks after the replacement of the GD by the GFD diet, the composition (beta-diversity) of gut microbiome in GS macaques started to change (p = 0.011) towards that of a normal macaque. Significance for alpha-diversity however, was not reached by the day 70 when the feeding experiment ended. Several inflammation-associated microRNAs (miR-203, -204, -23a, -23b and -29b) were upregulated (p < 0.05) in jejunum of 4 biopsied GS macaques fed GD with predicted binding sites on 16S ribosomal RNA of Lactobacillus reuteri (accession number: NR_025911), Prevotella stercorea (NR_041364) and Streptococcus luteciae (AJ297218) that were overrepresented in feces. Additionally, claudin-1, a validated tight junction protein target of miR-29b was significantly downregulated in jejunal epithelium of GS macaques. Taken together, we predict that with the introduction of effective treatments in future studies the diversity of gut microbiomes in GS macaques will approach those of healthy individuals. Further studies are needed to elucidate the regulatory pathways of inflammatory miRNAs in intestinal mucosa of GS macaques and to correlate their expression with gut dysbiosis. |
topic |
celiac gluten gut microbiome microbiota dysbiosis rhesus macaque metagenomics 16S rRNA miRNA chronic inflammation |
url |
http://www.mdpi.com/2072-6643/8/11/684 |
work_keys_str_mv |
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