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Gut Microbial Changes in Diabetic db/db Mice and Recovery of Microbial Diversity upon Pirfenidone Treatment

The leptin receptor-deficient db/db mouse model is an accepted in vivo model to study obesity, type 2 diabetes, and diabetic kidney disease. Healthy gastrointestinal (GI) microbiota has been linked to weight loss, improved glycemic control, and physiological benefits. We investigated the effect of v...

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Autores principales: Singh, Harinder, Miyamoto, Satoshi, Darshi, Manjula, Torralba, Manolito G., Kwon, Keehwan, Sharma, Kumar, Pieper, Rembert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564638/
https://www.ncbi.nlm.nih.gov/pubmed/32899353
http://dx.doi.org/10.3390/microorganisms8091347
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author Singh, Harinder
Miyamoto, Satoshi
Darshi, Manjula
Torralba, Manolito G.
Kwon, Keehwan
Sharma, Kumar
Pieper, Rembert
author_facet Singh, Harinder
Miyamoto, Satoshi
Darshi, Manjula
Torralba, Manolito G.
Kwon, Keehwan
Sharma, Kumar
Pieper, Rembert
author_sort Singh, Harinder
collection PubMed
description The leptin receptor-deficient db/db mouse model is an accepted in vivo model to study obesity, type 2 diabetes, and diabetic kidney disease. Healthy gastrointestinal (GI) microbiota has been linked to weight loss, improved glycemic control, and physiological benefits. We investigated the effect of various drugs on the GI microbiota of db/db mice as compared to control db/m mice. Treatment with long-acting pirfenidone (PFD) increased gut microbial diversity in diabetic db/db mice. Firmicutes, the most abundant phylum in db/m mice, decreased significantly in abundance in db/db mice but showed increased abundance with long-acting PFD treatment. Several bacterial taxa, including Lactobacillus and some Bacteroides, were less abundant in db/db mice and more abundant in long-acting-PFD-treated db/db mice. Long-acting PFD treatment reduced the abundance of Akkermansia muciniphila (5%) as compared to db/db mice (~15%). We conclude that gut microbial dysbiosis observed in db/db mice was partially reversed by long-acting PFD treatment and hypothesize that PFD has beneficial effects, in part, via its influence on the gut microbial metabolite profile. In quantitatively assessing urine metabolites, we observed a high abundance of diabetic ketoacidosis biomarkers, including 3-hydroxybutyric acid and acetoacetic acid in db/db mice, which were less abundant in the long-acting-PFD-treated db/db mice.
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spelling pubmed-75646382020-10-29 Gut Microbial Changes in Diabetic db/db Mice and Recovery of Microbial Diversity upon Pirfenidone Treatment Singh, Harinder Miyamoto, Satoshi Darshi, Manjula Torralba, Manolito G. Kwon, Keehwan Sharma, Kumar Pieper, Rembert Microorganisms Article The leptin receptor-deficient db/db mouse model is an accepted in vivo model to study obesity, type 2 diabetes, and diabetic kidney disease. Healthy gastrointestinal (GI) microbiota has been linked to weight loss, improved glycemic control, and physiological benefits. We investigated the effect of various drugs on the GI microbiota of db/db mice as compared to control db/m mice. Treatment with long-acting pirfenidone (PFD) increased gut microbial diversity in diabetic db/db mice. Firmicutes, the most abundant phylum in db/m mice, decreased significantly in abundance in db/db mice but showed increased abundance with long-acting PFD treatment. Several bacterial taxa, including Lactobacillus and some Bacteroides, were less abundant in db/db mice and more abundant in long-acting-PFD-treated db/db mice. Long-acting PFD treatment reduced the abundance of Akkermansia muciniphila (5%) as compared to db/db mice (~15%). We conclude that gut microbial dysbiosis observed in db/db mice was partially reversed by long-acting PFD treatment and hypothesize that PFD has beneficial effects, in part, via its influence on the gut microbial metabolite profile. In quantitatively assessing urine metabolites, we observed a high abundance of diabetic ketoacidosis biomarkers, including 3-hydroxybutyric acid and acetoacetic acid in db/db mice, which were less abundant in the long-acting-PFD-treated db/db mice. MDPI 2020-09-03 /pmc/articles/PMC7564638/ /pubmed/32899353 http://dx.doi.org/10.3390/microorganisms8091347 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Singh, Harinder
Miyamoto, Satoshi
Darshi, Manjula
Torralba, Manolito G.
Kwon, Keehwan
Sharma, Kumar
Pieper, Rembert
Gut Microbial Changes in Diabetic db/db Mice and Recovery of Microbial Diversity upon Pirfenidone Treatment
title Gut Microbial Changes in Diabetic db/db Mice and Recovery of Microbial Diversity upon Pirfenidone Treatment
title_full Gut Microbial Changes in Diabetic db/db Mice and Recovery of Microbial Diversity upon Pirfenidone Treatment
title_fullStr Gut Microbial Changes in Diabetic db/db Mice and Recovery of Microbial Diversity upon Pirfenidone Treatment
title_full_unstemmed Gut Microbial Changes in Diabetic db/db Mice and Recovery of Microbial Diversity upon Pirfenidone Treatment
title_short Gut Microbial Changes in Diabetic db/db Mice and Recovery of Microbial Diversity upon Pirfenidone Treatment
title_sort gut microbial changes in diabetic db/db mice and recovery of microbial diversity upon pirfenidone treatment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564638/
https://www.ncbi.nlm.nih.gov/pubmed/32899353
http://dx.doi.org/10.3390/microorganisms8091347
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