Characterization of local gut microbiome and intestinal transcriptome responses to rosiglitazone treatment in diabetic db/db mice

Mette Simone Aae Madsen, Rikke Veggerby Grønlund, John Eid, Mikkel Christensen-Dalsgaard, Morten Otto Alexander Sommer, Kristoffer Rigbolt, Martin Rønn Madsen, Jacob Jelsing, Niels Vrang, Henrik H. Hansen, Martin Tue Mikkelsen

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Abstract

The gut microbiota has been implicated in the therapeutic effects of antidiabetics. It is unclear if antidiabetics directly influences gut microbiome-host interaction. Oral peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists, such as rosiglitazone, are potent insulin sensitizers used in the treatment of type 2 diabetes (T2D). PPAR-γ is abundantly expressed in the intestine, making it possible that PPAR-γ agonists directly influences gut microbiome-host homeostasis. The presented study therefore aimed to characterize local gut microbiome and intestinal transcriptome responses in diabetic db/db mice following rosiglitazone treatment. Diabetic B6.BKS(D)- Leprdb/J (db/db) mice (8 weeks of age) received oral dosing once daily with vehicle (n = 12) or rosiglitazone (3 mg/kg, n = 12) for 8 weeks. Gut segments (duodenum, jejunum, ileum, caecum, and colon) were sampled for paired analysis of gut microbiota and host transcriptome signatures using full-length bacterial 16S rRNA sequencing and RNA sequencing (n = 5–6 per group). Treatment with rosiglitazone improved glucose homeostasis without influencing local gut microbiome composition in db/db mice. In contrast, rosiglitazone promoted marked changes in ileal and colonic gene expression signatures associated with peroxisomal and mitochondrial lipid metabolism, carbohydrate utilization and immune regulation. In conclusion, rosiglitazone treatment markedly affected transcriptional markers of intestinal lipid metabolism and immune regulation but had no effect on the gut microbiome in diabetic db/db mice.
Original languageEnglish
Article number110966
JournalBiomedicine and Pharmacotherapy
Volume133
ISSN1950-6007
DOIs
Publication statusPublished - 2021

Keywords

  • Peroxisome proliferator-activated receptor-γ
  • Diabetes
  • Mouse model
  • Gut microbiome
  • Gut transcriptome
  • Gut segment

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