Progression of diabetes is associated with changes in the ileal transcriptome and ileal‐colon morphology in the UC Davis Type 2 Diabetes Mellitus rat

Abstract Deterioration in glucose homeostasis has been associated with intestinal dysbiosis, but it is not known how metabolic dysregulation alters the gastrointestinal environment. We investigated how the progression of diabetes alters ileal and colonic epithelial mucosal structure, microbial abund...

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Autores principales:	Brian D. Piccolo, James L. Graham, Ping Kang, Christopher E. Randolph, Kartik Shankar, Laxmi Yeruva, Renee Fox, Michael S. Robeson, Becky Moody, Tanya LeRoith, Kimber L. Stanhope, Sean H. Adams, Peter J. Havel
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	crypt diabetes microbiome RNA‐seq UCD‐T2DM rat villi Physiology QP1-981
Acceso en línea:	https://doaj.org/article/c68b4547c4934ed29e8abdfeca5bbe3f
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spelling	oai:doaj.org-article:c68b4547c4934ed29e8abdfeca5bbe3f2021-11-27T15:48:30ZProgression of diabetes is associated with changes in the ileal transcriptome and ileal‐colon morphology in the UC Davis Type 2 Diabetes Mellitus rat2051-817X10.14814/phy2.15102https://doaj.org/article/c68b4547c4934ed29e8abdfeca5bbe3f2021-11-01T00:00:00Zhttps://doi.org/10.14814/phy2.15102https://doaj.org/toc/2051-817XAbstract Deterioration in glucose homeostasis has been associated with intestinal dysbiosis, but it is not known how metabolic dysregulation alters the gastrointestinal environment. We investigated how the progression of diabetes alters ileal and colonic epithelial mucosal structure, microbial abundance, and transcript expression in the University of California Davis Type 2 Diabetes Mellitus (UCD‐T2DM) rat model. Male UCD‐T2DM rats (age ~170 days) were included if <1‐month (n = 6, D1M) or 3‐month (n = 6, D3M) post‐onset of diabetes. Younger nondiabetic UCD‐T2DM rats were included as a nondiabetic comparison (n = 6, ND, age ~70 days). Ileum villi height/crypt depths and colon crypt depths were assessed by histology. Microbial abundance of colon content was measured with 16S rRNA sequencing. Ileum and colon transcriptional abundances were analyzed using RNA sequencing. Ileum villi height and crypt depth were greater in D3M rats compared to ND. Colon crypt depth was greatest in D3M rats compared to both ND and D1M rats. Colon abundances of Akkermansia and Muribaculaceae were lower in D3M rats relative to D1M, while Oscillospirales, Phascolarctobacterium, and an unidentified genus of Lachnospiraceae were higher. Only two transcripts were altered by diabetes advancement within the colon; however, 2039 ileal transcripts were altered. Only colonic abundances of Sptlc3, Enpp7, Slc7a15, and Kctd14 had more than twofold changes between D1M and D3M rats. The advancement of diabetes in the UCD‐T2DM rat results in a trophic effect on the mucosal epithelia and was associated with regulation of gastrointestinal tract RNA expression, which appears more pronounced in the ileum relative to the colon.Brian D. PiccoloJames L. GrahamPing KangChristopher E. RandolphKartik ShankarLaxmi YeruvaRenee FoxMichael S. RobesonBecky MoodyTanya LeRoithKimber L. StanhopeSean H. AdamsPeter J. HavelWileyarticlecryptdiabetesmicrobiomeRNA‐seqUCD‐T2DM ratvilliPhysiologyQP1-981ENPhysiological Reports, Vol 9, Iss 22, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	crypt diabetes microbiome RNA‐seq UCD‐T2DM rat villi Physiology QP1-981
spellingShingle	crypt diabetes microbiome RNA‐seq UCD‐T2DM rat villi Physiology QP1-981 Brian D. Piccolo James L. Graham Ping Kang Christopher E. Randolph Kartik Shankar Laxmi Yeruva Renee Fox Michael S. Robeson Becky Moody Tanya LeRoith Kimber L. Stanhope Sean H. Adams Peter J. Havel Progression of diabetes is associated with changes in the ileal transcriptome and ileal‐colon morphology in the UC Davis Type 2 Diabetes Mellitus rat
description	Abstract Deterioration in glucose homeostasis has been associated with intestinal dysbiosis, but it is not known how metabolic dysregulation alters the gastrointestinal environment. We investigated how the progression of diabetes alters ileal and colonic epithelial mucosal structure, microbial abundance, and transcript expression in the University of California Davis Type 2 Diabetes Mellitus (UCD‐T2DM) rat model. Male UCD‐T2DM rats (age ~170 days) were included if <1‐month (n = 6, D1M) or 3‐month (n = 6, D3M) post‐onset of diabetes. Younger nondiabetic UCD‐T2DM rats were included as a nondiabetic comparison (n = 6, ND, age ~70 days). Ileum villi height/crypt depths and colon crypt depths were assessed by histology. Microbial abundance of colon content was measured with 16S rRNA sequencing. Ileum and colon transcriptional abundances were analyzed using RNA sequencing. Ileum villi height and crypt depth were greater in D3M rats compared to ND. Colon crypt depth was greatest in D3M rats compared to both ND and D1M rats. Colon abundances of Akkermansia and Muribaculaceae were lower in D3M rats relative to D1M, while Oscillospirales, Phascolarctobacterium, and an unidentified genus of Lachnospiraceae were higher. Only two transcripts were altered by diabetes advancement within the colon; however, 2039 ileal transcripts were altered. Only colonic abundances of Sptlc3, Enpp7, Slc7a15, and Kctd14 had more than twofold changes between D1M and D3M rats. The advancement of diabetes in the UCD‐T2DM rat results in a trophic effect on the mucosal epithelia and was associated with regulation of gastrointestinal tract RNA expression, which appears more pronounced in the ileum relative to the colon.
format	article
author	Brian D. Piccolo James L. Graham Ping Kang Christopher E. Randolph Kartik Shankar Laxmi Yeruva Renee Fox Michael S. Robeson Becky Moody Tanya LeRoith Kimber L. Stanhope Sean H. Adams Peter J. Havel
author_facet	Brian D. Piccolo James L. Graham Ping Kang Christopher E. Randolph Kartik Shankar Laxmi Yeruva Renee Fox Michael S. Robeson Becky Moody Tanya LeRoith Kimber L. Stanhope Sean H. Adams Peter J. Havel
author_sort	Brian D. Piccolo
title	Progression of diabetes is associated with changes in the ileal transcriptome and ileal‐colon morphology in the UC Davis Type 2 Diabetes Mellitus rat
title_short	Progression of diabetes is associated with changes in the ileal transcriptome and ileal‐colon morphology in the UC Davis Type 2 Diabetes Mellitus rat
title_full	Progression of diabetes is associated with changes in the ileal transcriptome and ileal‐colon morphology in the UC Davis Type 2 Diabetes Mellitus rat
title_fullStr	Progression of diabetes is associated with changes in the ileal transcriptome and ileal‐colon morphology in the UC Davis Type 2 Diabetes Mellitus rat
title_full_unstemmed	Progression of diabetes is associated with changes in the ileal transcriptome and ileal‐colon morphology in the UC Davis Type 2 Diabetes Mellitus rat
title_sort	progression of diabetes is associated with changes in the ileal transcriptome and ileal‐colon morphology in the uc davis type 2 diabetes mellitus rat
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/c68b4547c4934ed29e8abdfeca5bbe3f
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Progression of diabetes is associated with changes in the ileal transcriptome and ileal‐colon morphology in the UC Davis Type 2 Diabetes Mellitus rat

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