Frontiers in immunology · 2026
DPP-4 inhibitors in drug-resistant epilepsy: a hypothesized mechanism via the gut microbiota-short-chain fatty acids-glucagon-like peptide-1 axis.
СтатьяОбзорНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Fu Xili, Xie Yinyin, Xie Yi, Han Aoya, Zhou Xinru, Zhang Shijie, Shen Changchang, Zhang Yuxuan, Wang Lina, Xie Nanchang
Аннотация
BACKGROUND: Drug-resistant epilepsy (DRE) affects approximately one-third of patients with epilepsy and remains a major therapeutic challenge.Recent studies have demonstrated significant gut microbiota dysbiosis in patients with DRE, and certain interventions targeting the gut microbiota demonstrate therapeutic efficacy. However, pharmacological interventions that precisely modulate the gut microbiota in DRE have not yet been fully explored.
OBJECTIVE: This review aims to propose a systematic hypothesis that Dipeptidyl peptidase-4 inhibitors (DPP-4is) may alleviate peripheral and central pathological damage by regulating the "gut microbiota-short-chain fatty acids (SCFAs) -glucagon-like peptide-1 (GLP-1) axis", thereby reducing susceptibility to DRE.
EVIDENCE: Existing studies indicate that: (1)DPP-4is possess neuroprotective effects in experimental epilepsy models, partly by enhancing endogenous GLP-1 signaling. (2)DPP-4is have been reported to modulate gut microbiota composition and increase the abundance of SCFA-producing bacteria in metabolic diseases. (3)SCFAs can promote GLP-1 secretion by activating free fatty acid receptors (FFAR2/3) and improve intestinal barrier function and inflammatory status in metabolic and neurodegeneration disease. However, it remains unclear whether this pathway mediates the effects of DPP-4is in epilepsy. (4)Enhanced peripheral GLP-1 signaling can further influence central nervous system homeostasis, including enhancing inhibitory synaptic transmission, attenuating neuroinflammation, oxidative stress, and inhibiting neuronal apoptosis, thereby reducing susceptibility to seizures.
CONCLUSION: By integrating cross-contextual evidence, we propose that DPP-4is may exert protective effects on DRE through gut microbiota-SCFAs-GLP-1 axis.
OBJECTIVE: This review aims to propose a systematic hypothesis that Dipeptidyl peptidase-4 inhibitors (DPP-4is) may alleviate peripheral and central pathological damage by regulating the "gut microbiota-short-chain fatty acids (SCFAs) -glucagon-like peptide-1 (GLP-1) axis", thereby reducing susceptibility to DRE.
EVIDENCE: Existing studies indicate that: (1)DPP-4is possess neuroprotective effects in experimental epilepsy models, partly by enhancing endogenous GLP-1 signaling. (2)DPP-4is have been reported to modulate gut microbiota composition and increase the abundance of SCFA-producing bacteria in metabolic diseases. (3)SCFAs can promote GLP-1 secretion by activating free fatty acid receptors (FFAR2/3) and improve intestinal barrier function and inflammatory status in metabolic and neurodegeneration disease. However, it remains unclear whether this pathway mediates the effects of DPP-4is in epilepsy. (4)Enhanced peripheral GLP-1 signaling can further influence central nervous system homeostasis, including enhancing inhibitory synaptic transmission, attenuating neuroinflammation, oxidative stress, and inhibiting neuronal apoptosis, thereby reducing susceptibility to seizures.
CONCLUSION: By integrating cross-contextual evidence, we propose that DPP-4is may exert protective effects on DRE through gut microbiota-SCFAs-GLP-1 axis.