Canagliflozin alters the gut, oral, and ocular surface microbiota of patients with type 2 diabetes mellitus

Abstract

BackgroundModifications in the gut microbiota may be a crucial factor in the efficacy of canagliflozin (Cana) in managing patients with type 2 diabetes mellitus (T2DM). However, the interplay between oral and ocular surface microbiota and this treatment remains poorly explored.AimThis study aimed to assess alterations in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment in patients with T2DM.MethodsIn this 30-day, controlled before-and-after study, 21 treatment-naïve patients with T2DM received sole treatment with Cana (100 mg/day), and were matched with 10 healthy controls based on gender and age. Using 16S rRNA sequencing, changes in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment were assessed and compared with those of healthy controls. Concurrently, diabetes-related clinical parameters were recorded over the study period. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR200034878).ResultsA noticeable shift was observed in the gut, oral, and ocular surface microbiota pre- and post-Cana treatment. The post-Cana treatment gut microbiota was more similar to that of the healthy controls. Network correlation analysis revealed that modifications in the gut, oral, and ocular surface microbiota were related to changes in clinical parameters, especially for the ocular surface microbiota.Clinical parametersA significant decrease in fasting plasma glucose (8.22 ± 2.19 vs 6.87 ± 1.09 mmol/L), glycated serum protein [291.00 (264.00, 353.00) vs 275.00 (251.00, 342.50) μmol/L], hemoglobin A1c (7.39 ± 1.18 vs 7.12 ± 1.33%), body mass index (25.32 ± 2.99 vs 24.83 ± 2.95 kg/m2), systolic blood pressure (129.05 ± 17.51 vs 123.43 ± 14.82 mmHg), and urinary creatinine [158.40 (74.75, 219.15) vs 79.70 (56.25, 138.10) μmmol/kg] levels was noted after 30-day Cana monotherapy (P < 0.05).Gut microbiomeTreatment with Cana resulted in an increase in the relative abundance of short-chain fatty acid (SCFA)-producing bacteria, particularly Lachnospiraceae UCG 004, Bacteroides, and Lachnospiraceae NK4A136 group.Oral microbiotaAfter Cana treatment, a significant increase of Prevotella and Veillonella, both of which are known to be closely associated with SCFAs, was observed.Ocular surface microbiotaPost-Cana administration, the ocular surface microbiota exhibited the most distinct changes in structure and composition. Remarkably, the majority of the increased ocular surface microbiota could produce SCFAs within the gut microbiota.ConclusionCana effectively improved the dysregulated glucose metabolism in patients with T2DM. This improvement can potentially be attributed to the restoration of balance among the gut, oral, and ocular surface microbial communities.Clinical trial registrationhttps://www.chictr.org.cn/showproj.html?proj=56487, identifier ChiCTR2000034878.

Canagliflozin attenuates kidney injury, gut-derived toxins, and gut microbiota imbalance in high-salt diet-fed Dahl salt-sensitive rats

“…It is increasingly recognized that the microbiome may affect the health and disease of the host [ 33 , 34 ]. Animal and clinical studies have shown that canagliflozin inhibits intestinal SGLT1, thereby altering the composition of the intestinal microbiota [ 17–19 , 35 , 36 ]. Our study also found canagliflozin-mediated changes in the gut microbiota in HSD-fed DSS rats.…”

Fecal microbiome predicts treatment response after the initiation of semaglutide or empagliflozin uptake

“…It has been shown that metformin alters the microbiome composition, but the microbiome is also a part of the mode of action of the drug and can modulate drug efficiency and toxicity [14][15] . Similarly to the firstchoice metformin, the action of novel glucagon-like peptide-1 receptor agonists (GLP-1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) toward the microbiome has been previously studied [16][17][18][19][20] . However, these studies have shown conflicting results regarding the changes in microbial diversity and abundance of microbial taxa.…”