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Type 2 diabetes (T2D) is a chronic metabolic disorder in which insulin resistance and impaired insulin secretion result in altered metabolite balance, specifically elevated levels of circulating glucose and succinate, which increases the risk of many pathologies, including periodontitis. Succinate, a tricarboxylic acid (TCA) cycle intermediate, can be produced and metabolized by both host cells and host microbiota, where elevated levels serve as an inflammation and pathogen threat signal through activating the succinate G protein‐coupled receptor, SUCNR1. Modulating succinate‐induced SUCNR1 signaling remains a promising therapeutic approach for pathologies resulting in elevated levels of succinate, such as T2D and periodontitis. Here, we demonstrate hyperglycemia and elevated intracellular succinate in a T2D mouse model and determine gut microbiome composition. Drawing on previous work demonstrating the ability of a novel SUCNR1 antagonist, compound 7a, to block inflammation and alleviate dysbiosis in a mouse model, we examined if compound 7a has an impact on the growth and virulence gene expression of bacterial and fungal human microbiota in vitro, and if 7a could reduce bone loss in a periodontitis‐induced mouse model. T2D mice harbored a significantly different gut microbiome, suggesting the altered metabolite profile of T2D causes shifts in host‐microbial community structure, with enrichment in succinate producers and consumers and mucin‐degrading bacteria. Bacterial and fungal cultures showed that 7a did not influence growth or virulence gene expression, suggesting the therapeutic effects of 7a are a direct result of 7a interacting with host cells and that alterations in microbial community structure are driven by reduced host SUCNR1 signaling. This work further suggests that targeting SUCNR1 signaling is a promising therapeutic approach in metabolic, inflammatory, or immune disorders with elevated succinate levels. [ABSTRACT FROM AUTHOR]

The effect of electronic cigarette (e‐cigarette) smoking, especially its long‐term impact on oral health, is poorly understood. Here, we conducted a longitudinal clinical study with two study visits, 6 months apart, to investigate the effect of e‐cigarette use on the bacterial community structure in the saliva of 101 periodontitis patients. Our data demonstrated that e‐cigarette use altered the oral microbiome in periodontitis patients, enriching members of the Filifactor, Treponema, and Fusobacterium taxa. For patients at the same periodontal disease stage, cigarette smokers and e‐cigarette smokers shared more similarities in their oral bacterial composition. E‐cigarette smoking may have a similar potential as cigarette smoking at altering the bacterial composition of saliva over time, leading to an increase in the relative abundance of periodontal disease‐associated pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum. The correlation analysis showed that certain genera, such as Dialister, Selenomonas, and Leptotrichia in the e‐cigarette smoking group, were positively correlated with the levels of proinflammatory cytokines, including IFN‐γ, IL‐1β, and TNF‐α. E‐cigarette use was also associated with elevated levels of proinflammatory cytokines such as IFN‐γ and TNF‐α, which contribute to oral microbiome dysbiosis and advanced disease state. [ABSTRACT FROM AUTHOR]

One‐third of epilepsy patients have drug‐resistant epilepsy (DRE), which is often complicated by polydrug toxicity and psychiatric and cognitive comorbidities. Advances in understanding the microbiome and gut‐brain‐axis are likely to shed light on epilepsy pathogenesis, anti‐seizure medication (ASM) resistance, and potential therapeutic targets. Gut dysbiosis is associated with inflammation, blood‐brain barrier disruption, and altered neuromodulators. High‐throughput and metagenomic sequencing has advanced the characterization of microbial species and functional pathways. DRE patients show altered gut microbiome composition compared to drug‐sensitive patients and healthy controls. The ketogenic and modified Atkins diets can reduce seizures in some patients with DRE. These low‐carbohydrate dietary therapies alter the taxonomic and functional composition of the gut microbiome, and composition varies between diet responders and nonresponders. Murine models suggest that specific phyla are necessary to confer efficacy from the diet, and antibiotic treatment may eliminate efficacy. The impact of diet might involve alterations in microbiota, promotion of select microbial interactions, and variance in brain neurotransmitter levels that then influence seizures. Understanding the mechanics of how diet manipulates seizures may suggest novel therapies. Most ASMs act on neuronal transmission via effects on ion channels and neurotransmitters. However, ASMs may also assert their effects via the gut microbiota. In animal models, the microbiota composition (eg, abundance of certain phyla) can vary with ASM active drug metabolites. Given the developing understanding of the gut microbiome in DRE, probiotics are another potential therapy. Probiotics alter the microbiota composition, and small studies suggest that these supplements can reduce seizures in some patients. DRE has enormous consequences to patients and society, and the gut microbiome holds promise as a potential therapeutic target. However, the exact mechanism and recognition of which patients are likely to be responders remain elusive. Further studies are warranted. [ABSTRACT FROM AUTHOR]

Enantiopure SPINOL-phosphoric acids exhibit high activities and excellent diastereo- and enantioselectivities in the catalysis of the three-component Povarov reaction of N-vinylcarbamate (III), anilines (II) and aldehydes (I). [ABSTRACT FROM AUTHOR]

The synthetic value of the present protocol is demonstrated by synthesis of (IX), the enantiomer of which is a potent orally active antihypertensive agent. [ABSTRACT FROM AUTHOR]

Asymmetric Pictet-Spengler reaction of tryptamine derivatives (II) with a diversity of aromatic and aliphatic aldehydes proceeds efficiently in the presence of SPINOL-phosphoric acids as organocatalysts. [ABSTRACT FROM AUTHOR]