Protective effects of dioscin against Parkinson's disease via regulating bile acid metabolism through remodeling gut microbiome/GLP-1 signaling

Zhang, Mao; Hui, Haochen; Zhao, Xin; Xu, Lina; Qi, Yan; Yin, Lianhong; Qu, Liping; Han, Lei; Peng, Jinyong

doi:10.1016/j.jpha.2023.06.007

Cited by 8 publications

(3 citation statements)

References 70 publications

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“…316 The alleviation of MPTP-induced gut dysbiosis and BAs alterations by dioscin treatment activates the intestinal TGR5 to stimulate GLP-1 secretion and upregulate GLP-1R expression in the brain, thereby attenuating glial activation and neurodegeneration. 390 Altogether, these studies underscore the potential of gut microbiome interventions to restore GLP-1 signaling and ameliorate PD pathogenesis.…”

Section: Ghrelinmentioning

confidence: 94%

“…Multiple in vivo studies have demonstrated the neuroprotective effects of UDCA and TUDCA in counteracting mitochondrial dysfunction, oxidative stress, and neuroinflammation within PD mouse models. [386][387][388][389][390][391][392] Moreover, the administration of a lowprotein high-carbohydrate diet effectively mitigated PD pathologies in MPTP-treated mice by increasing the serum concentrations of TUDCA. 393 These encouraging results have prompted two clinical trials, NCT03840005 (phase II) and NCT02967250 (phase I), which investigate the application of UDCA in PD patients.…”

Section: Gut Microbiota-derived Metabolites In Neurodegenerative Dise...mentioning

confidence: 99%

“…Importantly, the co-administration of UDCA and dioscin further enhanced the neuroprotective effects of dioscin. 390 GLP-1 is an incretin hormone that plays a pivotal role in stimulating insulin secretion and lowering blood glucose levels, making it highly relevant in the context of neurodegenerative diseases. 395 The administration of GLP-1 receptor agonist inhibited microglial activation, prevented microglial-mediated conversion of astrocytes into the neurotoxic A1 phenotype, and effectively protected against α-synucleinopathy-induced neurodegeneration.…”

Section: Gut Microbiota-derived Metabolites In Neurodegenerative Dise...mentioning

confidence: 99%

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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Loh,

Mak,

Tan

et al. 2024

Sig Transduct Target Ther

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The human gastrointestinal tract is populated with a diverse microbial community. The vast genetic and metabolic potential of the gut microbiome underpins its ubiquity in nearly every aspect of human biology, including health maintenance, development, aging, and disease. The advent of new sequencing technologies and culture-independent methods has allowed researchers to move beyond correlative studies toward mechanistic explorations to shed light on microbiome–host interactions. Evidence has unveiled the bidirectional communication between the gut microbiome and the central nervous system, referred to as the “microbiota–gut–brain axis”. The microbiota–gut–brain axis represents an important regulator of glial functions, making it an actionable target to ameliorate the development and progression of neurodegenerative diseases. In this review, we discuss the mechanisms of the microbiota–gut–brain axis in neurodegenerative diseases. As the gut microbiome provides essential cues to microglia, astrocytes, and oligodendrocytes, we examine the communications between gut microbiota and these glial cells during healthy states and neurodegenerative diseases. Subsequently, we discuss the mechanisms of the microbiota–gut–brain axis in neurodegenerative diseases using a metabolite-centric approach, while also examining the role of gut microbiota-related neurotransmitters and gut hormones. Next, we examine the potential of targeting the intestinal barrier, blood–brain barrier, meninges, and peripheral immune system to counteract glial dysfunction in neurodegeneration. Finally, we conclude by assessing the pre-clinical and clinical evidence of probiotics, prebiotics, and fecal microbiota transplantation in neurodegenerative diseases. A thorough comprehension of the microbiota–gut–brain axis will foster the development of effective therapeutic interventions for the management of neurodegenerative diseases.

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Section: Ghrelinmentioning

confidence: 94%

Section: Gut Microbiota-derived Metabolites In Neurodegenerative Dise...mentioning

confidence: 99%

Section: Gut Microbiota-derived Metabolites In Neurodegenerative Dise...mentioning

confidence: 99%

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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Loh,

Mak,

Tan

et al. 2024

Sig Transduct Target Ther

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Isomeric differentiation of bile acids using three‐dimensional MS² spectrum

Niu,

Zhou,

Zhao

et al. 2024

J Chinese Chemical Soc

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Bile acids (BAs) currently occupy the research hotspot because of their unreplaceable physiological functions as well as their unique abilities to reflect the physiopathological status. It is always challenging to characterize BAs‐submetabolome using LC–MS/MS, primarily attributing to the high‐level structural diversity. The key obstructing confirmative identification is isomeric identification because of the inherent “isomer‐blind” disadvantage of MS/MS. The isomerism styles of BAs are broadly divided into: type‐I, 5α‐H and 5β‐H epimers; type‐II, α‐OH and β‐OH epimers; type‐III, C‐OH positional isomers; and type‐IV, hybrid isomers bearing two or more isomerism fashions. Herein, we aim to comprehensively pursue isomer‐selective clues for BAs through constructing three‐dimensional MS2 (3D‐MS2) spectrum that was accomplished by fortifying energy‐resolved MS (ER‐MS) program as the new dimension. The breakdown graphs of primary MS2 spectral signals composed of 3D‐MS2 spectrum namely full collision energy ramp (FCER)‐MS2 spectrum for each BA species after appropriate normalization, and seven isomeric BAs covering all isomerism styles were utilized as representative cases. After recording MS2 spectra with progressive CE levels, differences were observed for their FCER‐MS2 spectra. Diagnostic fragment ions (DFIs) occurred within type‐I, type‐II, type‐III or type‐IV isomers, and noteworthily, 2.02 Da neutral loss discriminated BAs containing cis‐6,7‐diol and trans‐6,7‐diol functional groups. Notably, the features such as the maximal relative ion intensity (RIImax) and optimal CE (OCE) enabled isomeric differentiation for all types, even type‐II and type‐III isomers. Above all, it is feasible to acquire in‐depth isomer‐selective MS/MS clues for BAs using FCER‐MS2 spectrum, regardless of the isomerism manner.

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Gut Microbiota-Induced Modulation of the Central Nervous System Function in Parkinson’s Disease Through the Gut-Brain Axis and Short-Chain Fatty Acids

Ni,

Tong,

et al. 2024

Mol Neurobiol

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Protective effects of dioscin against Parkinson's disease via regulating bile acid metabolism through remodeling gut microbiome/GLP-1 signaling

Cited by 8 publications

References 70 publications

Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Isomeric differentiation of bile acids using three‐dimensional MS² spectrum

Gut Microbiota-Induced Modulation of the Central Nervous System Function in Parkinson’s Disease Through the Gut-Brain Axis and Short-Chain Fatty Acids

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Protective effects of dioscin against Parkinson's disease via regulating bile acid metabolism through remodeling gut microbiome/GLP-1 signaling

Cited by 8 publications

References 70 publications

Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases

Isomeric differentiation of bile acids using three‐dimensional MS2 spectrum

Gut Microbiota-Induced Modulation of the Central Nervous System Function in Parkinson’s Disease Through the Gut-Brain Axis and Short-Chain Fatty Acids

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Isomeric differentiation of bile acids using three‐dimensional MS² spectrum