Analyses of gut microbiota and plasma bile acids enable stratification of patients for antidiabetic treatment

Gu, Yuchao; Wang, Xiaokai; Li, Junhua; Zhang, Yifei; Huang, Zhong; Liu, Ruixin; Zhang, Dongya; Feng, Qiang; Xie, Xiaoyan; Hong, Jing; Ren, Huahui; Liu, Wei; Ma, Jing; Su, Qing; Zhang, Hongmei; Yang, Jialin; Wang, Xiaoling; Zhao, Xinjie; Gu, Weiqiong; Bi, Yufang; Peng, Yongde; Xu, Xiaoqiang; Xia, Huihua; Li, Fang; Xu, Xun; Yang, Huanming; Xu, Guowang; Madsen, Lise; Kristiansen, Karsten; Ning, Guang; Wang, Weiqing

doi:10.1038/s41467-017-01682-2

Cited by 339 publications

(404 citation statements)

References 59 publications

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“…Abundant evidence has demonstrated the important roles of bile acids in glucose homeostasis . Total plasma bile acid concentrations are higher in obese and T2D subjects than in healthy controls, whereas bile acid pools are also regulated by glucose‐lowering drugs such as metformin and acarbose . In the present study, we showed that saxagliptin, a DPP‐4 inhibitor, significantly increased serum concentrations of CA, GCA, GCDCA, GDCA, and GUDCA in both NW and OW/OB T2D patients, and with CDCA and DCA levels also increasing in the OW/OB group.…”

Section: Discussionsupporting

confidence: 58%

“…Human studies have demonstrated that the bile acid composition in diabetic or obese patients differs from that in normal populations . Moreover, metabolic surgeries and glucose‐lowering drugs, such as metformin and acarbose, have been reported to regulate the bile acid pool contributing to glucose control . This evidence suggests that bile acids may be involved in the pathophysiological process of metabolic diseases.…”

Section: Introductionmentioning

confidence: 99%

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Saxagliptin alters bile acid profiles and yields metabolic benefits in drug‐naïve overweight or obese type 2 diabetes patient

Wen

Liu

et al. 2019

Journal of Diabetes

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Background The aim of the present study was to investigate the metabolic benefits of saxagliptin and its effects on serum bile acids (BAs) in normal weight and overweight/obese drug‐naïve type 2 diabetes (T2D) patients. Methods In all, 282 drug‐naïve T2D patients (123 normal weight [NW], with body mass index [BMI] between 19.0 and <25.0 kg/m2; 159 overweight/obese [OW/OB], with BMI ≥25.0 kg/m2) were enrolled in the study and treated with saxagliptin 5 mg daily for 24 weeks. Serum BAs were assayed by liquid chromatography with tandem mass spectrometry. Results At 24 weeks, HbA1c was significantly reduced in both groups, but the HbA1c levels were lower in the OW/OB than NW group. Moreover, significant decreases were seen at 24 weeks in C‐reactive protein (CRP), aspartate aminotransferase, alanine aminotransferase, waist circumference, and systolic blood pressure in the OW/OB group. Interestingly, cholic acid, glycocholic acid, glycochenodeoxycholic acid, glycodeoxycholic acid (GDCA), and glycoursodeoxycholic acid (GUDCA) were increased in both groups after treatment, whereas chenodeoxycholic acid and deoxycholic acid (DCA) were specifically increased in the OW/OB group. Increased DCA and GDCA concentrations were significantly associated with decreased HbA1c or fasting blood glucose and CRP levels, whereas increased GDCA and GUDCA concentrations were associated with decreased waist circumference in the OW/OB group during treatment. In the NW group, increased GUDCA concentrations were significantly associated with a decrease in HbA1c. Conclusions Type 2 diabetes patients with OW/OB exhibited greater improvement in glycemic control and additional metabolic benefits after saxagliptin treatment. Saxagliptin significantly increased the BA pool, and DCA and GDCA were associated with metabolic improvements in OW/OB T2D patients.

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Section: Discussionsupporting

confidence: 58%

Section: Introductionmentioning

confidence: 99%

Saxagliptin alters bile acid profiles and yields metabolic benefits in drug‐naïve overweight or obese type 2 diabetes patient

Wen

Liu

et al. 2019

Journal of Diabetes

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“…172,173 Metformin reduced the abundance of B. fragilis in patients with type 2 diabetes and increased the concentration of bile acid glycoursodeoxycholic acid. 175 174 Similarly, acarbose is recommended for the treatment of type 2 diabetes.…”

Section: Metformin and Acarbosementioning

confidence: 99%

“…Treatment with acarbose increased the relative abundances of Lactobacillus and Bifidobacterium and reduced Bacteroides, thereby changing bile acid metabolism. 175…”

Section: Metformin and Acarbosementioning

confidence: 99%

The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing

Song

Khan

et al. 2019

Intl Journal of Cancer

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The prevalence of colorectal cancer (CRC) has markedly increased worldwide in the last decade. Alterations of bile acid metabolism and gut microbiota have been reported to play vital roles in intestinal carcinogenesis. About trillions of bacteria have inhabited in the human gut and maintained the balance of host metabolism. Bile acids are one of numerous metabolites that are synthesized in the liver and further metabolized by the gut microbiota, and are essential in maintaining the normal gut microbiota and lipid digestion. Multiple receptors such as FXR, GPBAR1, PXR, CAR and VDR act as sensors of bile acids have been reported. In this review, we mainly discussed interplay between bile acid metabolism and gut microbiota in intestinal carcinogenesis. We then summarized the critical role of bile acids receptors involving in CRC, and also addressed the rationale of multiple interventions for CRC management by regulating bile acids–microbiota axis such as probiotics, metformin, ursodeoxycholic acid and fecal microbiota transplantation. Thus, by targeting the bile acids–microbiota axis may provide novel therapeutic modalities in CRC prevention and treatment.

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“…Thus, the microbiota-metabolites interactions are important to maintain the host health and wellbeing. Integrative data analysis of gut microbiome and metabolome can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases (e.g., autoimmune diseases, inflammatory bowel disease [5] , cancers [6] , type 2 diabetes and obesity [7] , cardiovascular disorders, and non-alcoholic fatty liver disease [8] ), and provide potential diagnostic and therapeutic targets [9] .…”

Section: Introductionmentioning

confidence: 99%

M²IA: a Web Server for Microbiome and Metabolome Integrative Analysis

Deng

et al. 2019

Preprint

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Background: In the last decade, integrative studies of microbiome and metabolome have experienced exponential growth in understanding their impact on human health and diseases. However, analyzing the resulting multi-omics data and their correlations remains a significant challenge in current studies due to the lack of a comprehensive computational tool to facilitate data integration and interpretation. In this study, we have developed a microbiome and metabolome integrative analysis pipeline (M 2 IA) to meet the urgent needs for tools that effectively integrate microbiome and metabolome data to derive biological insights.Results: M 2 IA streamlines the integrative data analysis between metabolome and microbiome, including both univariate analysis and multivariate modeling methods.KEGG-based functional analysis of microbiome and metabolome are provided to explore their biological interactions within specific metabolic pathways. The functionality of M 2 IA was demonstrated using TwinsUK cohort data with 1116 fecal metabolites and 16s rRNA microbiome from 786 individuals. As a result, we identified two important pathways, i.e., the benzoate degradation and phosphotransferase system, were closely associated with obesity from both metabolome and microbiome.Conclusions: M 2 IA is a public available web server (http://m2ia.met-bioinformatics.cn) with the capability to investigate the complex interplay between microbiome and metabolome, and help users to develop mechanistic hypothesis for nutritional and personalized therapies of diseases.

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Analyses of gut microbiota and plasma bile acids enable stratification of patients for antidiabetic treatment

Cited by 339 publications

References 59 publications

Saxagliptin alters bile acid profiles and yields metabolic benefits in drug‐naïve overweight or obese type 2 diabetes patient

Saxagliptin alters bile acid profiles and yields metabolic benefits in drug‐naïve overweight or obese type 2 diabetes patient

The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing

M²IA: a Web Server for Microbiome and Metabolome Integrative Analysis

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Analyses of gut microbiota and plasma bile acids enable stratification of patients for antidiabetic treatment

Cited by 339 publications

References 59 publications

Saxagliptin alters bile acid profiles and yields metabolic benefits in drug‐naïve overweight or obese type 2 diabetes patient

Saxagliptin alters bile acid profiles and yields metabolic benefits in drug‐naïve overweight or obese type 2 diabetes patient

The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: An old story, yet mesmerizing

M2IA: a Web Server for Microbiome and Metabolome Integrative Analysis

Contact Info

Product

Resources

About

M²IA: a Web Server for Microbiome and Metabolome Integrative Analysis