Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer’s disease progression

Cell Research, Год журнала: 2019, Номер 29(10), С. 787 - 803

Опубликована: Сен. 6, 2019

Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer's disease (AD) progression, yet role of microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link neuroinflammation progression. Using mouse models, discovered that, during alteration composition leads to peripheral accumulation phenylalanine isoleucine, which stimulates differentiation proliferation pro-inflammatory T helper 1 (Th1) cells. The brain-infiltrated Th1 immune cells are associated with M1 microglia activation, contributing AD-associated neuroinflammation. Importantly, elevation isoleucine concentrations increase cell frequency blood were also observed two small independent cohorts patients mild cognitive impairment (MCI) due AD. Furthermore, GV-971, sodium oligomannate that demonstrated solid consistent cognition improvement phase 3 clinical trial China, suppresses phenylalanine/isoleucine accumulation, harnesses reverses impairment. Together, our findings highlight dysbiosis-promoted progression suggest novel strategy for therapy by remodelling microbiota.

Язык: Английский

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The gut microbiota in anxiety and depression – A systematic review

Clinical Psychology Review, Год журнала: 2020, Номер 83, С. 101943 - 101943

Опубликована: Окт. 29, 2020

Язык: Английский

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Brain-Gut-Microbiota Axis in Alzheimer’s Disease

Journal of Neurogastroenterology and Motility, Год журнала: 2019, Номер 25(1), С. 48 - 60

Опубликована: Янв. 10, 2019

Disturbances along the brain-gut-microbiota axis may significantly contribute to pathogenesis of neurodegenerative disorders. Alzheimer's disease (AD) is most frequent cause dementia characterized by a progressive decline in cognitive function associated with formation amyloid beta (Aβ) plaques and neurofibrillary tangles. Alterations gut microbiota composition induce increased permeability barrier immune activation leading systemic inflammation, which turn impair blood-brain promote neuroinflammation, neural injury, ultimately neurodegeneration. Recently, Aβ has also been recognized as an antimicrobial peptide participating innate response. However, dysregulated state, reveal harmful properties. Importantly, bacterial amyloids through molecular mimicry elicit cross-seeding misfolding microglial priming. The seeding propagation occur at different levels axis. potential mechanisms spreading include neuron-to-neuron or distal neuron spreading, direct crossing via other cells astrocytes, fibroblasts, microglia, system cells. A growing body experimental clinical data confirms key role dysbiosis microbiota-host interactions convergence gut-derived inflammatory response together aging poor diet elderly AD. Modification food-based therapy probiotic supplementation create new preventive therapeutic options

Язык: Английский

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Regulation of Neurotransmitters by the Gut Microbiota and Effects on Cognition in Neurological Disorders

Nutrients, Год журнала: 2021, Номер 13(6), С. 2099 - 2099

Опубликована: Июнь 19, 2021

Emerging evidence indicates that gut microbiota is important in the regulation of brain activity and cognitive functions. Microbes mediate communication among metabolic, peripheral immune, central nervous systems via microbiota–gut–brain axis. However, it not well understood how microbiome neurons mutually interact or these interactions affect normal functioning cognition. We summarize mechanisms whereby regulate production, transportation, neurotransmitters. also discuss dysbiosis affects function, especially neurodegenerative diseases such as Alzheimer’s disease Parkinson’s disease.

Язык: Английский

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Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer's disease

Life Sciences, Год журнала: 2020, Номер 264, С. 118627 - 118627

Опубликована: Окт. 22, 2020

Язык: Английский

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Alzheimer’s Disease Microbiome Is Associated with Dysregulation of the Anti-Inflammatory P-Glycoprotein Pathway

mBio, Год журнала: 2019, Номер 10(3)

Опубликована: Май 6, 2019

Studies of the intestinal microbiome and AD have demonstrated associations with composition at genus level among matched cohorts. We move this body literature forward by more deeply investigating via metagenomics comparing patients against those without dementia other types. also exploit machine learning approaches that combine both metagenomic clinical data. Finally, our functional studies using stool samples from elders demonstrate how c can affect health dysregulation P-glycoprotein pathway. contributes directly to inflammatory disorders intestine. Since has been long thought be linked chronic bacterial infections as a possible etiology, findings therefore fill gap in knowledge field research identifying nexus between microbiome, loss homeostasis, inflammation may underlie neurodegenerative disorder.

Язык: Английский

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Gut Microbiota and Dysbiosis in Alzheimer’s Disease: Implications for Pathogenesis and Treatment

Molecular Neurobiology, Год журнала: 2020, Номер 57(12), С. 5026 - 5043

Опубликована: Авг. 22, 2020

Understanding how gut flora influences gut-brain communications has been the subject of significant research over past decade. The broadening term "microbiota-gut-brain axis" from "gut-brain underscores a bidirectional communication system between and brain. microbiota-gut-brain axis involves metabolic, endocrine, neural, immune pathways which are crucial for maintenance brain homeostasis. Alterations in composition microbiota associated with multiple neuropsychiatric disorders. Although causal relationship dysbiosis neural dysfunction remains elusive, emerging evidence indicates that may promote amyloid-beta aggregation, neuroinflammation, oxidative stress, insulin resistance pathogenesis Alzheimer's disease (AD). Illustration mechanisms underlying regulation by pave way developing novel therapeutic strategies AD. In this narrative review, we provide an overview their dysregulation Novel insights into modification as preventive or approach AD highlighted.

Язык: Английский

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Diet and Inflammation in Cognitive Ageing and Alzheimer’s Disease

Current Nutrition Reports, Год журнала: 2019, Номер 8(2), С. 53 - 65

Опубликована: Апрель 4, 2019

Nutrition is known to modulate the immune system and may alter neuroinflammatory processes implicated in pathogenesis of Alzheimer's disease (AD) progression neurodegeneration. Here, we review evidence for healthy dietary patterns age-related cognition discuss potential actions diet on cognitive function. Anti-inflammatory such as Mediterranean (MD) approaches stop hypertension (DASH) be neuroprotective. Several components consumed MD DASH (omega-3 fatty acids, antioxidants polyphenols) can inhibit neuroinflammation associated with AD. diets also attenuate via indirect pathways from gut microbiome systemic circulation. Diet influence ageing several inflammatory pathways. However, data human studies are lacking exact mechanisms linking function remain elusive. Further intervention required investigate diet-associated neurological change earliest through latest stages decline. Furthermore, incorporation neuroimaging measures would advance current understanding mechanistic effects modification brain.

Язык: Английский

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Inflammatory bowel disease is associated with higher dementia risk: a nationwide longitudinal study

Gut, Год журнала: 2020, Номер 70(1), С. 85 - 91

Опубликована: Июнь 23, 2020

Increasing evidence supports reciprocal communication between the enteric and central nervous system in disease, termed 'gut-brain axis'. Recent findings suggest a connection IBD development of Parkinson's disease. The role dementia, another insidious neurodegenerative disorder, has not been explored.

Язык: Английский

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Probiotic Bifidobacterium lactis V9 Regulates the Secretion of Sex Hormones in Polycystic Ovary Syndrome Patients through the Gut-Brain Axis

mSystems, Год журнала: 2019, Номер 4(2)

Опубликована: Апрель 15, 2019

Although a few studies have investigated the intestinal microbiota of women with polycystic ovary syndrome (PCOS), functional and metabolic mechanisms microbes associated PCOS, as well potential microbial biomarkers, not yet been identified. To address this gap, we designed two-phase experiment in which performed shotgun metagenomic sequencing monitored parameters, gut-brain mediators, sex hormones PCOS patients. In first stage, identified an imbalance patients, observing that Faecalibacterium, Bifidobacterium, Blautia were significantly more abundant control group, whereas Parabacteroides Clostridium enriched group. second impact probiotic Bifidobacterium lactis V9 on microbiome, 14 Notably, observed levels luteinizing hormone (LH) LH/follicle-stimulating (LH/FSH) decreased 9 volunteers, short-chain fatty acids (SCFAs) increased markedly. contrast, changes indices mentioned above indistinct remaining 5 volunteers. The results analysis number viable cells two groups highly consistent clinical SCFA results. Therefore, effective host gut colonization was crucial for its ability to function probiotic. Finally, propose mechanism describing how probiotics regulate by manipulating microbiome IMPORTANCE Polycystic (PCOS) is common disorder among reproductive age worldwide. Through experiment, revealed By binning annotating sequences into species (MGS), 61 MGSs PCOS-related biomarkers. microbiota, microbiotas participating patients exhibited inconsistent response intake B. regulates

Язык: Английский

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