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

Wen, Li; Liu, Ruixin; Li, Xuelin; Tao, Bei; Zhai, Nan; Wang, Xiaolin; Li, Qi; Zhang, Yifei; Gu, Weiqiong; Wang, Weiqing; Ning, Guang

doi:10.1111/1753-0407.12956

Cited by 13 publications

(10 citation statements)

References 47 publications

(98 reference statements)

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“…Our data demonstrated that specific gut microbiota related metabolites contributed to the interpretation of the connection between the fruit-related microbiota and T2D. Previous studies demonstrated that treatment with specific microbiota derived secondary bile acids (obeticholic acid, DCA, and GDCA) in patients with T2D improved insulin sensitivity and HbAlc, which was consistent with our present study [40,41]. Another study found that fecal sebacic acid was decreased in IBD patients [42].…”

Section: Discussionsupporting

confidence: 92%

Dietary fruit and vegetable intake, gut microbiota, and type 2 diabetes: results from two large human cohort studies

Jiang

Sun

et al. 2020

BMC Med

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Background Little is known about the inter-relationship among fruit and vegetable intake, gut microbiota and metabolites, and type 2 diabetes (T2D) in human prospective cohort study. The aim of the present study was to investigate the prospective association of fruit and vegetable intake with human gut microbiota and to examine the relationship between fruit and vegetable-related gut microbiota and their related metabolites with type 2 diabetes (T2D) risk. Methods This study included 1879 middle-age elderly Chinese adults from Guangzhou Nutrition and Health Study (GNHS). Baseline dietary information was collected using a validated food frequency questionnaire (2008–2013). Fecal samples were collected at follow-up (2015–2019) and analyzed for 16S rRNA sequencing and targeted fecal metabolomics. Blood samples were collected and analyzed for glucose, insulin, and glycated hemoglobin. We used multivariable linear regression and logistic regression models to investigate the prospective associations of fruit and vegetable intake with gut microbiota and the association of the identified gut microbiota (fruit/vegetable-microbiota index) and their related fecal metabolites with T2D risk, respectively. Replications were performed in an independent cohort involving 6626 participants. Results In the GNHS, dietary fruit intake, but not vegetable, was prospectively associated with gut microbiota diversity and composition. The fruit-microbiota index (FMI, created from 31 identified microbial features) was positively associated with fruit intake (p < 0.001) and inversely associated with T2D risk (odds ratio (OR) 0.83, 95%CI 0.71–0.97). The FMI-fruit association (p = 0.003) and the FMI-T2D association (OR 0.90, 95%CI 0.84–0.97) were both successfully replicated in the independent cohort. The FMI-positive associated metabolite sebacic acid was inversely associated with T2D risk (OR 0.67, 95%CI 0.51–0.86). The FMI-negative associated metabolites cholic acid (OR 1.35, 95%CI 1.13–1.62), 3-dehydrocholic acid (OR 1.30, 95%CI 1.09–1.54), oleylcarnitine (OR 1.77, 95%CI 1.45–2.20), linoleylcarnitine (OR 1.66, 95%CI 1.37–2.05), palmitoylcarnitine (OR 1.62, 95%CI 1.33–2.02), and 2-hydroglutaric acid (OR 1.47, 95%CI 1.25–1.72) were positively associated with T2D risk. Conclusions Higher fruit intake-associated gut microbiota and metabolic alteration were associated with a lower risk of T2D, supporting the public dietary recommendation of adopting high fruit intake for the T2D prevention.

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Section: Discussionsupporting

confidence: 92%

Dietary fruit and vegetable intake, gut microbiota, and type 2 diabetes: results from two large human cohort studies

Jiang

Sun

et al. 2020

BMC Med

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“…25 In addition, increased serum GUDCA levels are associated with decreased hemoglobin A1c and waist circumference in patients with T2DM. 26 The above evidence…”

Section: Discussionmentioning

confidence: 87%

“… 25 In addition, increased serum GUDCA levels are associated with decreased hemoglobin A1c and waist circumference in patients with T2DM. 26 The above evidence indicates that GUDCA has potential metabolic beneficial effects. However, in our study, GUDCA level in the GDM group was increased and positively correlated with blood glucose and triglyceride levels.…”

Section: Discussionmentioning

confidence: 94%

“…A recent study reported that GUDCA can act as an intestinal farnesol X receptor antagonist, significantly reducing weight gain and restoring glucose intolerance and insulin resistance in a diet‐induced obesity mouse model 25 . In addition, increased serum GUDCA levels are associated with decreased hemoglobin A1c and waist circumference in patients with T2DM 26 …”

Section: Discussionmentioning

confidence: 99%

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Alterations of gut microbiota‐derived metabolites in gestational diabetes mellitus and clinical significance

Gao

Chen

et al. 2022

Clinical Laboratory Analysis

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Background The change in the characteristics of the gut microbiota is linked to gestational diabetes mellitus (GDM). However, whether and how the gut microbiota‐derived metabolites change in GDM is uncertain. Here, we aimed to determine associations between the gut microbiota‐derived metabolites and GDM. Methods Using targeted metabolomics approaches, 7 types of short‐chain fatty acids (SCFAs), 38 types of bile acids (BAs), and 5 types of trimethylamine N‐oxide (TMAO), and its derivatives of serum samples were obtained from pregnant women with GDM (n = 24), and healthy pregnant controls (HC, n = 28) were detected to identify the metabolic signature of GDM to investigate the potential biomarkers. Moreover, we assessed the associations between gut microbiota‐derived metabolites and clinical parameters. Results In our study, the gut microbiota‐derived metabolites signatures were significantly different between GDM and HC. Quantitative results showed the levels of isobutyric acid, isovaleric acid, valeric acid, caproic acid, GUDCA, THDCA + TUDCA, and LCA‐3S were significantly higher in GDM, but the level of TMAO and its derivatives did not change significantly. Some altered gut microbiota‐derived metabolites were significantly correlated with glucose and lipid levels. Receiver‐operating characteristic (ROC) analysis of generalized linear models showed that gut microbiota‐derived metabolites may be potential biomarkers of GDM. Conclusion This study highlights gut microbiota‐derived metabolites alterations in GDM and correlation of the clinical indicators, which provides a new direction for future studies aiming to novel serum biomarker for early detection or target of drug therapy of GDM.

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“…In contrast to the work of Humbert et al., phospholipid‐depletion SPE was shown by other groups to give higher recovery and reproducibility than protein precipitation and reversed‐phase SPE [20,31]. Alternative sample preparation methods include those omitting the SPE step, for instance, incubation of samples at low temperatures with ice‐cold methanol and centrifugation [32], lyophilization [10,33,34], or ultrafiltration [35]. Sun et al.…”

Section: Bile Acid Analysismentioning

confidence: 99%

Analysis of bile acids in human biological samples by microcolumn separation techniques: A review

2020

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Bile acids are a group of compounds essential for lipid digestion and absorption with a steroid skeleton and a carboxylate side chain usually conjugated to glycine or taurine. Bile acids are regulatory molecules for a number of metabolic processes and can be used as biomarkers of various disorders. Since the middle of the twentieth century, the detection of bile acids has evolved from simple qualitative analysis to accurate quantification in complicated mixtures. Advanced methods are required to characterize and quantify individual bile acids in these mixtures. This article overviews the literature from the last two decades (2000-2020) and focuses on bile acid analysis in various human biological samples. The methods for sample preparation, including the sample treatment of conventional (blood plasma, blood serum, and urine) and unconventional samples (bile, saliva, duodenal/gastric juice, feces, etc.) are shortly discussed. Eventually, the focus is on novel analytical approaches and methods for each particular biological sample, providing an overview of the microcolumn separation techniques, such as high-performance liquid chromatography, gas chromatography, and capillary electrophoresis, used in their analysis. This is followed by a discussion on selected clinical applications.

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

Cited by 13 publications

References 47 publications

Dietary fruit and vegetable intake, gut microbiota, and type 2 diabetes: results from two large human cohort studies

Dietary fruit and vegetable intake, gut microbiota, and type 2 diabetes: results from two large human cohort studies

Alterations of gut microbiota‐derived metabolites in gestational diabetes mellitus and clinical significance

Analysis of bile acids in human biological samples by microcolumn separation techniques: A review

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