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Microorganisms
Volume 8
Issue 9
10.3390/microorganisms8091347
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Article

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

by
Harinder Singh
1,*,
Satoshi Miyamoto
2,
Manjula Darshi
2,
Manolito G. Torralba
3,
Keehwan Kwon
1,
Kumar Sharma
2 and
Rembert Pieper
1
1
J. Craig Venter Institute, 9605 Medical Center Drive, Suite 150, Rockville, MD 20850, USA
2
Department of Medicine, University of Texas Health, San Antonio, TX 77030, USA
3
J. Craig Venter Institute, 4120 Capricorn Lane, La Jolla, CA 92037, USA
*
Author to whom correspondence should be addressed.
Microorganisms 2020, 8(9), 1347; https://doi.org/10.3390/microorganisms8091347
Submission received: 4 August 2020 / Revised: 29 August 2020 / Accepted: 2 September 2020 / Published: 3 September 2020
(This article belongs to the Special Issue Gut Microbiota: Its Role in Diabetes and Obesity)
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Abstract

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.
Keywords: gut microbiome; db/db mouse model; pirfenidone; cholecystokinin; type 2 diabetes; diabetic nephropathy; diabetic complications; kidney metabolism; metagenomics gut microbiome; db/db mouse model; pirfenidone; cholecystokinin; type 2 diabetes; diabetic nephropathy; diabetic complications; kidney metabolism; metagenomics

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MDPI and ACS Style

Singh, H.; Miyamoto, S.; Darshi, M.; Torralba, M.G.; Kwon, K.; Sharma, K.; Pieper, R. Gut Microbial Changes in Diabetic db/db Mice and Recovery of Microbial Diversity upon Pirfenidone Treatment. Microorganisms 2020, 8, 1347. https://doi.org/10.3390/microorganisms8091347

AMA Style

Singh H, Miyamoto S, Darshi M, Torralba MG, Kwon K, Sharma K, Pieper R. Gut Microbial Changes in Diabetic db/db Mice and Recovery of Microbial Diversity upon Pirfenidone Treatment. Microorganisms. 2020; 8(9):1347. https://doi.org/10.3390/microorganisms8091347

Chicago/Turabian Style

Singh, Harinder, Satoshi Miyamoto, Manjula Darshi, Manolito G. Torralba, Keehwan Kwon, Kumar Sharma, and Rembert Pieper. 2020. "Gut Microbial Changes in Diabetic db/db Mice and Recovery of Microbial Diversity upon Pirfenidone Treatment" Microorganisms 8, no. 9: 1347. https://doi.org/10.3390/microorganisms8091347

APA Style

Singh, H., Miyamoto, S., Darshi, M., Torralba, M. G., Kwon, K., Sharma, K., & Pieper, R. (2020). Gut Microbial Changes in Diabetic db/db Mice and Recovery of Microbial Diversity upon Pirfenidone Treatment. Microorganisms, 8(9), 1347. https://doi.org/10.3390/microorganisms8091347

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