TY - JOUR

T1 - Deciphering unique and shared interactions between the human gut microbiota and oral antidiabetic drugs

AU - Ren, Huahui

AU - Shi, Zhun

AU - Yang, Fangming

AU - Wang, Shujie

AU - Yuan, Fengyi

AU - Li, Tingting

AU - Li, Min

AU - Zhu, Jiahui

AU - Li, Junhua

AU - Wu, Kui

AU - Zhang, Yifei

AU - Ning, Guang

AU - Kristiansen, Karsten

AU - Wang, Weiqing

AU - Gu, Yanyun

AU - Zhong, Huanzi

N1 - Funding Information: We appreciate the research teams from the endocrinology and metabolic departments of Shenzhen People's Hospital for their contributions to the clinical trial and data collection. The sequencing of this work was supported by China National GeneBank. This work was supported by grants from the National Key Research and Development Project of China (2022YFC2505203) and Guangdong Provincial Key Laboratory of Human Disease Genomics (2020B1212070028).

PY - 2024

Y1 - 2024

N2 - Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by hyperglycemia and increased insulin resistance, and is closely associated with gut microbial dysbiosis [1]. Oral antidiabetic drugs (OADs), such as metformin, sulfonylureas, alpha-glucosidase inhibitors (AGIs), and dipeptidyl-peptidase-4 (DPP-4) inhibitors are commonly prescribed for glycemic control in T2D patients, yet the effectiveness of such treatment displays considerable variations across individuals.A number of studies have demonstrated that various OADs significantly alter the gut microbiota, which in turn have profound effects on host metabolism underlying in part the clinical benefits in individuals with T2D [2-6]. The administration of metformin significantly increased the relative abundance of Akkermansia muciniphila [5]. Acarbose, an AGI, was found to dramatically alter the gut microbial composition by elevating Bifidobacterium and depleting Bacteroides spp. [4, 7]. Our recent study demonstrated that a 12-week berberine treatment significantly reduced the abundance of Ruminococcus bromii, a secondary bile acid (SBA)-producer, and plasma levels of deoxycholic acid (DCA), associated with improved glucose homeostasis [6]. Additionally, two studies, including ours, have revealed associations between the baseline gut microbiota and therapeutic outcomes of DPP-4 inhibitors [7, 8].However, considerable disparities persist in the reported gut microbial alterations in response to different OADs, possibly due to the variations in ethnicity, sample size, and metagenomic methodology across studies. A comprehensive evaluation using consistent pipelines is clearly warranted to understand bidirectional interactions between OADs and the gut microbiota, as well as their potential impacts on drug efficacy.

AB - Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by hyperglycemia and increased insulin resistance, and is closely associated with gut microbial dysbiosis [1]. Oral antidiabetic drugs (OADs), such as metformin, sulfonylureas, alpha-glucosidase inhibitors (AGIs), and dipeptidyl-peptidase-4 (DPP-4) inhibitors are commonly prescribed for glycemic control in T2D patients, yet the effectiveness of such treatment displays considerable variations across individuals.A number of studies have demonstrated that various OADs significantly alter the gut microbiota, which in turn have profound effects on host metabolism underlying in part the clinical benefits in individuals with T2D [2-6]. The administration of metformin significantly increased the relative abundance of Akkermansia muciniphila [5]. Acarbose, an AGI, was found to dramatically alter the gut microbial composition by elevating Bifidobacterium and depleting Bacteroides spp. [4, 7]. Our recent study demonstrated that a 12-week berberine treatment significantly reduced the abundance of Ruminococcus bromii, a secondary bile acid (SBA)-producer, and plasma levels of deoxycholic acid (DCA), associated with improved glucose homeostasis [6]. Additionally, two studies, including ours, have revealed associations between the baseline gut microbiota and therapeutic outcomes of DPP-4 inhibitors [7, 8].However, considerable disparities persist in the reported gut microbial alterations in response to different OADs, possibly due to the variations in ethnicity, sample size, and metagenomic methodology across studies. A comprehensive evaluation using consistent pipelines is clearly warranted to understand bidirectional interactions between OADs and the gut microbiota, as well as their potential impacts on drug efficacy.

U2 - 10.1002/imt2.179

DO - 10.1002/imt2.179

M3 - Comment/debate

AN - SCOPUS:85187510999

VL - 3

JO - iMeta

JF - iMeta

SN - 2770-5986

IS - 2

M1 - e179

ER -