Intestinal microbial metabolites in human metabolism and type 2 diabetes

Herrema, Hilde; Niess, Jan Hendrik

doi:10.1007/s00125-020-05268-4

Cited by 70 publications

(47 citation statements)

References 140 publications

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“…The role of gut microbiota-derived metabolites in the development of cardiovascular disease has gained recent attention [ 11 ], particularly in individuals with T2D [ 34 ]. Nevertheless, the association of TMAO with risk of cardiovascular mortality in subjects with T2D has not being sufficiently studied.…”

Section: Discussionmentioning

confidence: 99%

Circulating Trimethylamine N-Oxide Is Associated with Increased Risk of Cardiovascular Mortality in Type-2 Diabetes: Results from a Dutch Diabetes Cohort (ZODIAC-59)

Flores‐Guerrero

Dijk

Connelly

et al. 2021

JCM

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Trimethylamine N-oxide (TMAO), a novel cardiovascular (CV) disease and mortality risk marker, is a gut microbiota-derived metabolite as well. Recently, plasma concentrations of branched-chain amino acids (BCAA) have been reported to be affected by microbiota. The association of plasma TMAO with CV mortality in Type 2 Diabetes (T2D) and its determinants are still incompletely described. We evaluated the association between plasma BCAA and TMAO, and the association of TMAO with CV mortality in T2D individuals. We used data of 595 participants (mean age 69.5 years) from the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) cohort were analyzed. Plasma TMAO and BCAA were measured with nuclear magnetic resonance spectroscopy. CV mortality risk was estimated using multivariable-adjusted Cox regression models. Cross-sectionally, TMAO was independently associated with BCAA standardized (Std) β = 0.18 (95% Confidence Interval (CI) 0.09; 0.27), p <0.001. During a median follow-up of 10 years, 113 CV deaths were recorded. In Cox regression analyses, adjusted for multiple clinical and laboratory variables including BCAA, TMAO was independently associated with CV mortality: adjusted hazard ratio (adjHR) 1.93 (95% CI 1.11; 3.34), p = 0.02 (for the highest vs. the lowest tertile of the TMAO distribution). The same was true for analyses with TMAO as continuous variable: adjHR 1.32 (95% CI 1.07; 1.63), p = 0.01 (per 1 SD increase). In contrast, BCAAs were not associated with increased CV mortality. In conclusion, higher plasma TMAO but not BCAA concentrations are associated with an increased risk of CV mortality in individuals with T2D, independent of clinical and biochemical risk markers.

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Section: Discussionmentioning

confidence: 99%

Circulating Trimethylamine N-Oxide Is Associated with Increased Risk of Cardiovascular Mortality in Type-2 Diabetes: Results from a Dutch Diabetes Cohort (ZODIAC-59)

Flores‐Guerrero

Dijk

Connelly

et al. 2021

JCM

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“…Numerous studies have demonstrated that the α-glucosidase inhibitory and α-amylase inhibitory activities of probiotics may be beneficial for glycemic regulation [ 28 , 29 ]. Probiotics have been reported to alleviate T2DM by regulating glucose metabolism and improving insulin sensitivity through several mechanisms, including the production of metabolites, such as SCFAs [ 30 , 31 ]. Some probiotic strains have been reported to produce bioactive components capable of inhibiting α-glucosidase activity [ 15 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Antidiabetic, Antioxidant Activity, and Probiotic Activities of Lactiplantibacillus plantarum and Lacticaseibacillus paracasei Strains

et al. 2021

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Diabetes, a chronic metabolic disorder, is characterized by persistent hyperglycemia. This study aimed to evaluate the hypoglycemic and antioxidant activities of lactic acid bacteria strains isolated from humans and food products and investigate the probiotic properties of the selected four strains. The hypoglycemic activity of the isolated strains was examined by evaluating the α-glucosidase and α-amylase inhibitory activities. The antioxidant activity was measured using the DPPH, ABTS, and FRAP assays. Four strains (Lactiplantibacillus plantarum MG4229, MG4296, MG5025, and Lacticaseibacillus paracasei MG5012) exhibited potent α-glucosidase inhibitory (>75%) and α-amylase inhibitory (>85%) activities, which were comparable to those of acarbose (>50%; 1000 μg/mL). Similarly, the radical scavenging and antioxidant activities of the four strains were comparable to those of ascorbic acid (50 μg/mL). Additionally, the probiotic properties of the four selected strains were examined based on acid and bile salt tolerance, auto-aggregation ability, and antibiotic resistance. The four strains were resistant to pH 2 (>50% of survivability) and 0.5% bile salt (>80% of survivability). Therefore, we suggest that the selected strains with hypoglycemic, antioxidant, probiotic properties can potentially prevent diabetes.

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“…Yet, further studies are needed to address whether alterations in gut microbiome in humans is a cause of type 2 diabetes or is an outcome of it. [ 93 , 95 , 96 , 97 , 98 ]…”

Section: Glucagon Signalingmentioning

confidence: 99%

Emerging Targets in Type 2 Diabetes and Diabetic Complications

et al. 2021

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Type 2 diabetes is a metabolic, chronic disorder characterized by insulin resistance and elevated blood glucose levels. Although a large drug portfolio exists to keep the blood glucose levels under control, these medications are not without side effects. More importantly, once diagnosed diabetes is rarely reversible. Dysfunctions in the kidney, retina, cardiovascular system, neurons, and liver represent the common complications of diabetes, which again lack effective therapies that can reverse organ injury. Overall, the molecular mechanisms of how type 2 diabetes develops and leads to irreparable organ damage remain elusive. This review particularly focuses on novel targets that may play role in pathogenesis of type 2 diabetes. Further research on these targets may eventually pave the way to novel therapies for the treatment-or even the prevention-of type 2 diabetes along with its complications.

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Intestinal microbial metabolites in human metabolism and type 2 diabetes

Cited by 70 publications

References 140 publications

Circulating Trimethylamine N-Oxide Is Associated with Increased Risk of Cardiovascular Mortality in Type-2 Diabetes: Results from a Dutch Diabetes Cohort (ZODIAC-59)

Circulating Trimethylamine N-Oxide Is Associated with Increased Risk of Cardiovascular Mortality in Type-2 Diabetes: Results from a Dutch Diabetes Cohort (ZODIAC-59)

In Vitro Antidiabetic, Antioxidant Activity, and Probiotic Activities of Lactiplantibacillus plantarum and Lacticaseibacillus paracasei Strains

Emerging Targets in Type 2 Diabetes and Diabetic Complications

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