Serum metabolic signatures of subclinical atherosclerosis in patients with type 2 diabetes mellitus: a preliminary study

Su, Jiaorong; Zhao, Qing; Zhao, Aihua; Wang, Jia; Zhu, Wei; Lu, Jingyi; Ma, Xiaojing

doi:10.1007/s00592-021-01717-7

Cited by 10 publications

(6 citation statements)

References 34 publications

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“…The quantitative analysis was using UPLC/TQ-MS (LC 1290, MS 6460, Agilent Technologies, USA) according to a protocol we previously established 56 . For serum samples pretreatment, 5 μL of each serum sample was mixed with 25 μL 160 mM 3-nitrophenylhydrazine-hydrochloride and 25 μL of 40 mM N-Ethyl-N′-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC·HCl) solution.…”

Section: Methodsmentioning

confidence: 99%

Gut microbiota-bile acid crosstalk contributes to the rebound weight gain after calorie restriction in mice

Wang

et al. 2022

Nat Commun

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Calorie restriction (CR) and fasting are common approaches to weight reduction, but the maintenance is difficult after resuming food consumption. Meanwhile, the gut microbiome associated with energy harvest alters dramatically in response to nutrient deprivation. Here, we reported that CR and high-fat diet (HFD) both remodeled the gut microbiota with similar microbial composition, Parabacteroides distasonis was most significantly decreased after CR or HFD. CR altered microbiota and reprogramed metabolism, resulting in a distinct serum bile acid profile characterized by depleting the proportion of non-12α-hydroxylated bile acids, ursodeoxycholic acid and lithocholic acid. Downregulation of UCP1 expression in brown adipose tissue and decreased serum GLP-1 were observed in the weight-rebound mice. Moreover, treatment with Parabacteroides distasonis or non-12α-hydroxylated bile acids ameliorated weight regain via increased thermogenesis. Our results highlighted the gut microbiota-bile acid crosstalk in rebound weight gain and Parabacteroides distasonis as a potential probiotic to prevent rapid post-CR weight gain.

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Section: Methodsmentioning

confidence: 99%

Gut microbiota-bile acid crosstalk contributes to the rebound weight gain after calorie restriction in mice

Wang

et al. 2022

Nat Commun

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“…Ankle-branchial index (ABI, ratio of systolic blood pressure in the ankle to that in the arm) has particularly proved to be a good measure of systemic atherosclerosis and serves as a risk indicator even in patients with CVD [ 11 ]. However, few studies have explored the metabolomic profile of ABI in either general populations or people with diabetes, and in those metabolomic studies where atherosclerosis was evaluated by other markers (e.g., pulse wave velocity), populations with diabetes were mainly small Asian groups [ 12 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

Serum metabolomic profiles associated with subclinical and clinical cardiovascular phenotypes in people with type 2 diabetes

Huang

Klarić

Krasauskaite

et al. 2022

Cardiovasc Diabetol

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Background Atherosclerotic cardiovascular diseases (CVD) is the leading cause of death in diabetes, but the full range of biomarkers reflecting atherosclerotic burden and CVD risk in people with diabetes is unknown. Metabolomics may help identify novel biomarkers potentially involved in development of atherosclerosis. We investigated the serum metabolomic profile of subclinical atherosclerosis, measured using ankle brachial index (ABI), in people with type 2 diabetes, compared with the profile for symptomatic CVD in the same population. Methods The Edinburgh Type 2 Diabetes Study is a cohort of 1,066 individuals with type 2 diabetes. ABI was measured at baseline, years 4 and 10, with cardiovascular events assessed at baseline and during 10 years of follow-up. A panel of 228 metabolites was measured at baseline using nuclear magnetic resonance spectrometry, and their association with both ABI and prevalent CVD was explored using univariate regression models and least absolute shrinkage and selection operator (LASSO). Metabolites associated with baseline ABI were further explored for association with follow-up ABI and incident CVD. Results Mean (standard deviation, SD) ABI at baseline was 0.97 (0.18, N = 1025), and prevalence of CVD was 35.0%. During 10-year follow-up, mean (SD) change in ABI was + 0.006 (0.178, n = 436), and 257 CVD events occurred. Lactate, glycerol, creatinine and glycoprotein acetyls levels were associated with baseline ABI in both univariate regression [βs (95% confidence interval, CI) ranged from − 0.025 (− 0.036, − 0.015) to − 0.023 (− 0.034, − 0.013), all p < 0.0002] and LASSO analysis. The associations remained nominally significant after adjustment for major vascular risk factors. In prospective analyses, lactate was nominally associated with ABI measured at years 4 and 10 after adjustment for baseline ABI. The four ABI-associated metabolites were all positively associated with prevalent CVD [odds ratios (ORs) ranged from 1.29 (1.13, 1.47) to 1.49 (1.29, 1.74), all p < 0.0002], and they were also positively associated with incident CVD [ORs (95% CI) ranged from 1.19 (1.02, 1.39) to 1.35 (1.17, 1.56), all p < 0.05]. Conclusions Serum metabolites relating to glycolysis, fluid balance and inflammation were independently associated with both a marker of subclinical atherosclerosis and with symptomatic CVD in people with type 2 diabetes. Additional investigation is warranted to determine their roles as possible etiological and/or predictive biomarkers for atherosclerotic CVD.

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“…41 Carotid intimamedia thickness (C-IMT), a proxy for subclinical atherosclerosis, was analysed in correlation with patients' serum metabolic pro les, it was found that deoxycholic acid and taurodeoxycholic acid (TDCA) levels were signi cantly higher in patients with abnormal C-IMT than in those with normal C-IMT. 42 The levels of TCDCA, TCA were increased in gingival tissues of patients with periodontitis and showed a positive correlation with periodontal clinical parameters. 43 These results suggest that CAP-induced changes in bile acids may contribute to the extent of atherosclerosis by affecting intestinal permeability.…”

Section: Discussionmentioning

confidence: 91%

Unveiling the Oral-Gut Connection: Chronic Periodontal Infection Accelerates Atherosclerosis via Gut Microbiota Dysbiosis and Altered Metabolites in apoE-/- Mice on a High-Fat Diet

Huang,

Gan,

Lin

et al. 2023

Preprint

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This study aimed to explore the impact of chronic apical periodontitis (CAP) on atherosclerosis in apoE−/− mice subjected to a high-fat diet (HFD). The investigation focused on gut microbiota, metabolites, and intestinal barrier function to uncover potential links between oral health and cardiovascular disease. In this research, CAP was found to exacerbate atherosclerosis in HFD-fed apoE−/− mice, as evident from increased plaque size and volume in arterial walls by Oil Red-O staning. 16S rRNA sequence uncovered significant alterations in gut microbiota, with harmful bacterial species thriving while beneficial ones declined. Metabolomic profiling indicated disruptions in lipid metabolism and primary bile acid synthesis, leading to elevated levels of taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), and tauroursodeoxycholic acid (TDCA). These metabolic shifts may contribute to atherosclerosis development. Furthermore, the study observed impairment in intestinal barrier function, characterized by reduced mucin expression and disrupted tight junction proteins. The increased intestinal permeability observed positively correlated with the extent of atherosclerotic lesions, emphasizing the significance of the intestinal barrier in cardiovascular health. In conclusion, this research underscores the intricate interplay between oral health, gut microbiota composition, metabolite profiles, and cardiovascular disease. It highlights the exacerbating effect of CAP on atherosclerosis in the context of a high-fat diet. These findings emphasize the importance of maintaining good oral hygiene as a potential preventive measure against cardiovascular issues, as well as the need for further investigations into the intricate mechanisms linking oral health, gut microbiota, and metabolic pathways in cardiovascular disease development.

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Serum metabolic signatures of subclinical atherosclerosis in patients with type 2 diabetes mellitus: a preliminary study

Cited by 10 publications

References 34 publications

Gut microbiota-bile acid crosstalk contributes to the rebound weight gain after calorie restriction in mice

Gut microbiota-bile acid crosstalk contributes to the rebound weight gain after calorie restriction in mice

Serum metabolomic profiles associated with subclinical and clinical cardiovascular phenotypes in people with type 2 diabetes

Unveiling the Oral-Gut Connection: Chronic Periodontal Infection Accelerates Atherosclerosis via Gut Microbiota Dysbiosis and Altered Metabolites in apoE-/- Mice on a High-Fat Diet

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