Vitamin B12 and gut-brain homeostasis in the pathophysiology of ischemic stroke

Roth, William; Mohamadzadeh, Mansour

doi:10.1016/j.ebiom.2021.103676

Cited by 48 publications

(26 citation statements)

References 79 publications

(74 reference statements)

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“…The Hcy, a key metabolite of methionine, is thought to participate in a variety of biological processes ( 18 – 20 ). Although how Hcy is involved in the pathogenesis of MMD is unclear, several possible mechanisms were reported in diseases.…”

Section: Discussionmentioning

confidence: 99%

Hyperhomocysteinemia Is a Predictor for Poor Postoperative Angiogenesis in Adult Patients With Moyamoya Disease

et al. 2022

Front. Neurol.

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Background and PurposesThe risk factors of poor postoperative angiogenesis in moyamoya disease (MMD) patients remain unknown. We aimed to investigate the association between hyperhomocysteinemia (HHcy) and postoperative angiogenesis of adult patients with MMD.MethodsA total of 138 adult patients with MMD were prospectively recruited from July 1 to December 31, 2019. After excluding 10 patients accepting conservative therapy and 77 individuals without postoperative digital subtraction angiography (DSA), all 51 MMD patients were enrolled, and 28 patients received bilateral operations separately. Patients were grouped according to postoperative angiogenesis and HHcy presentation, respectively. Clinical data and laboratory examinations were compared. Potential risk factors were evaluated by univariate and multivariate logistic regression analysis. Nomogram was further performed. The biological functions of homocysteine (Hcy) were explored in vitro.ResultsComparing to the normal, patients with poor postoperative angiogenesis were higher in serum Hcy (p = 0.004), HHcy ratio (p = 0.011), creatinine (Cr) (p < 0.001), uric acid (UA) (p = 0.036), Triglyceride (p = 0.001), high-density lipoprotein cholesterol (HDL-C) (p = 0.001), low-density lipoprotein cholesterol (LDL-C) (p = 0.009), ApoA (p = 0.022), apolipoprotein B (ApoB) (p = 0.013). Furthermore, HHcy was more common in men (p = 0.003) than women. Logistic analysis results showed that Hcy (OR = 0.817, 95% CI = 0.707–0.944, p = 0.006) was an independent risk factor. HHcy and Cr were significantly associated with poor postoperative angiogenesis in MMD patients. Further, Hcy could inhibit the proliferation, migration, and tube formation of human brain microvascular endothelial cells (HBMECs), which can be reversed by vascular endothelial growth factor (VEGF).ConclusionThe HHcy was significantly correlated with poor postoperative angiogenesis in adult patients with MMD. Hcy significantly inhibits HBMECs proliferation, migration, and tube formation. Furthermore, VEGF could reverse the inhibition effect induced by Hcy. Lowering the level of Hcy may be beneficial for postoperative MMD patients. Focusing on the pathophysiology and mechanism of HHcy might help to guide postoperative clinical management.

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Section: Discussionmentioning

confidence: 99%

Hyperhomocysteinemia Is a Predictor for Poor Postoperative Angiogenesis in Adult Patients With Moyamoya Disease

et al. 2022

Front. Neurol.

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“…Vitamin B is a group of water-soluble essential nutrients that serve as precursors of essential cofactors in numerous metabolic pathways. Vitamin B deficiency would cause a series of diseases including cognitive dysfunction, neuropathy, cardiovascular disease (CVD), and osteoporosis (1)(2)(3)(4)(5)(6)(7). Humans cannot synthesize these vitamins de novo, so vitamin B is mainly supplied through diet and, to a lesser extent, synthesized by gut microbiota.…”

Section: Introductionmentioning

confidence: 99%

Intermediate role of gut microbiota in vitamin B nutrition and its influences on human health

Wan

Zheng²,

Zhu³

et al. 2022

Front. Nutr.

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Vitamin B consists of a group of water-soluble micronutrients that are mainly derived from the daily diet. They serve as cofactors, mediating multiple metabolic pathways in humans. As an integrated part of human health, gut microbiota could produce, consume, and even compete for vitamin B with the host. The interplay between gut microbiota and the host might be a crucial factor affecting the absorbing processes of vitamin B. On the other hand, vitamin B supplementation or deficiency might impact the growth of specific bacteria, resulting in changes in the composition and function of gut microbiota. Together, the interplay between vitamin B and gut microbiota might systemically contribute to human health. In this review, we summarized the interactions between vitamin B and gut microbiota and tried to reveal the underlying mechanism so that we can have a better understanding of its role in human health.

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“…The associated metabolites are dimethylbenzimidazole, 2’-deoxyuridine-5’-monophosphate and 2-(4-hydroxyphenyl)-propionic acid, respectively. Interestingly, dimethylbenzimidazole is a component of vitamin B12 that has been reported to suppress microglial activation 69 . Also, among 4 predicted AD-associated GPCR genes of two AD-derived metabolites, C3AR1 (encoding protein C3AR, paired with 3-hydroxybutyric acid) was differentially expressed in DAM, which is in line with a previous study 66 .…”

Section: Resultsmentioning

confidence: 99%

Comprehensive characterization of multi-omic landscapes between gut-microbiota metabolites and the G-protein-coupled receptors in Alzheimer’s disease

Qiu

Hou

Zhou

et al. 2022

Preprint

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Accumulating evidence suggests that gut-microbiota metabolites contribute to human disease pathophysiology, yet the host receptors that sense these metabolites are largely unknown. Here, we developed a systems pharmacogenomics framework that integrates machine learning (ML), AlphaFold2-derived structural pharmacology, and multi-omics to identify disease-relevant metabolites derived from gut-microbiota with non-olfactory G-protein-coupled receptors (GPCRome). Specifically, we evaluated 1.68 million metabolite-protein pairs connecting 408 human GPCRs and 516 gut metabolites using an Extra Trees algorithm-improved structural pharmacology strategy. Using genetics-derived Mendelian randomization and multi-omics (including transcriptomic and proteomic) analyses, we identified likely causal GPCR targets (C3AR, FPR1, GALR1 and TAS2R60) in Alzheimer's disease (AD). Using three-dimensional structural fingerprint analysis of the metabolite-GPCR complexome, we identified over 60% of the allosteric pockets of orphan GPCR models for gut metabolites in the GPCRome, including AD-related orphan GPCRs (GPR27, GPR34, and GPR84). We additionally identified the potential targets (e.g., C3AR) of two AD-related metabolites (3-hydroxybutyric acid and Indole-3-pyruvic acid) and four metabolites from AD-related bacterium Eubacterium rectale, and also showed that tridecylic acid is a candidate ligand for orphan GPR84 in AD. In summary, this study presents a systems pharmacogenomics approach that serves to uncover the GPCR molecular targets of gut microbiota in AD and likely many other human diseases if broadly applied.

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Vitamin B12 and gut-brain homeostasis in the pathophysiology of ischemic stroke

Cited by 48 publications

References 79 publications

Hyperhomocysteinemia Is a Predictor for Poor Postoperative Angiogenesis in Adult Patients With Moyamoya Disease

Hyperhomocysteinemia Is a Predictor for Poor Postoperative Angiogenesis in Adult Patients With Moyamoya Disease

Intermediate role of gut microbiota in vitamin B nutrition and its influences on human health

Comprehensive characterization of multi-omic landscapes between gut-microbiota metabolites and the G-protein-coupled receptors in Alzheimer’s disease

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