Causal relationship between gut microflora and dementia: a Mendelian randomization study

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 15, 2024

Background Numerous pertinent investigations have demonstrated a correlation between gut microflora (GM) and the occurrence of dementia. However, causal connection GM dementia its subtypes has not yet been clarified. Objective To explore association dementia, including subtypes, two-sample Mendelian randomization (TSMR) analysis was used. Methods Our data comes from Genome-Wide Association Study (GWAS). The principal approach employed for study inverse-variance weighted method, supplemented by four methods: MR-Egger, median, simple mode, mode. This followed Cochrane’s Q test, MR-Egger intercept MR-PRESSO global leave-one-out as sensitivity validation. Results Twenty-one GMs associated with any Alzheimer’s disease, vascular Lewy body Parkinson’s under other disease classifications were derived analysis, 21 passed tests. Conclusion We confirmed relationship specific flora increased or decreased risk provided new ideas preventive, diagnostic, therapeutic interventions mediated microbiota.

Language: Английский

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Targeting lipid metabolism: novel insights and therapeutic advances in pancreatic cancer treatment

Lipids in Health and Disease, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 13, 2025

Lipid metabolism in cancer is characterized by dysregulated lipid regulation and utilization, critical for promoting tumor growth, survival, resistance to therapy. Pancreatic (PC) a highly aggressive malignancy of the gastrointestinal tract that has dismal 5-year survival rate less than 10%. Given essential function pancreas digestion, progression severely disrupts its function. Standard treatments PC such as surgical resection, chemotherapy, radiotherapy. However, these therapies often face significant challenges, including biochemical recurrence drug resistance. limitations, new therapeutic approaches are being developed target metabolism. Dysregulation cholesterol biosynthesis alterations fatty acids (FAs), palmitate, stearate, omega-3, omega-6, have been observed pancreatic cancer. These lipids serve energy sources, signaling molecules, components cell membranes. Their accumulation fosters an immunosuppressive microenvironment supports proliferation metastasis. Moreover, dysregulation within immune cells, particularly T impairs surveillance weakens body's defenses against Abnormal also contributes PC. Despite targeting may offer promising strategy. By enhancing peroxidation, induction ferroptosis—a form regulated death—could impair cells hinder disease progression.

Language: Английский

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Oral Administration of Lactobacillus gasseri and Lacticaseibacillus rhamnosus Ameliorates Amyloid Beta (Aβ)-Induced Cognitive Impairment by Improving Synaptic Function Through Regulation of TLR4/Akt Pathway

Antioxidants, Journal Year: 2025, Volume and Issue: 14(2), P. 139 - 139

Published: Jan. 24, 2025

This study investigated the anti-amnesic effects of Lactobacillus gasseri (L. gasseri) MG4247 and Lacticaseibacillus rhamnosus rhamnosus) MG4644 in amyloid beta (Aβ)-induced mice. We confirmed that oral administration L. ameliorated cognitive impairment Aβ-induced mice using Y-maze, passive avoidance, Morris water maze tests. Oral protected antioxidant system by regulating superoxide dismutase levels, reduced glutathione malondialdehyde contents. Similarly, they attenuated mitochondrial function decreasing reactive oxygen species levels increasing membrane potential ATP levels. In addition, regulated neuroinflammation neurotoxicity modulating Toll-like receptor 4 (TLR4)/protein kinase B (Akt) pathway. As a result, enhanced synaptic acetylcholine contents, acetylcholinesterase activity, expression synaptic-function-related proteins such as AChE, ChAT, SYP, PSD-95, GAP-43. Furthermore, improved dysbiosis promoting growth beneficial bacteria while suppressing harmful bacteria. Therefore, these results suggest may be used probiotics to prevent impairment.

Language: Английский

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Radix Bupleuri aqueous extract attenuates MK801-induced schizophrenia-like symptoms in mice: Participation of intestinal flora

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 172, P. 116267 - 116267

Published: Feb. 16, 2024

Schizophrenia (SCZ) is a psychotic mental disorder characterized by cognitive, behavioral, and social impairments. However, current pharmacological treatment regimens are subpar in terms of effectiveness. This study aimed to investigate the function Radix Bupleuri aqueous extract SCZ mouse models. The model was established MK-801 injection feeding or combined antibiotics. significantly improved aberrant behaviors neuronal damage mice, upregulated SYP PSD-95 expression BDNF levels hippocampal homogenates, down-regulated DA 5-HT levels, suppressed microglial activation mice. Moreover, integrity intestinal tract barrier. 16 S rRNA sequencing feces showed that modulated composition gut flora. Lactobacillus abundance decreased mice reversed administration which exhibited significant negative correlation with IL-6, IL-1β, DA, 5-HT, positive tissues. Parabacteroides Alloprevotella increased It administration, BDNF. In conclusion, attenuates inflammatory response tissues modulates neurotransmitter exerting its neuroprotective effect SCZ. Meanwhile, alteration flora may be involved this process, expected an underlying therapeutic option treating

Language: Английский

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Alleviation of Cognitive Impairment-like Behaviors, Neuroinflammation, Colitis, and Gut Dysbiosis in 5xFAD Transgenic and Aged Mice by Lactobacillus mucosae and Bifidobacterium longum

Nutrients, Journal Year: 2023, Volume and Issue: 15(15), P. 3381 - 3381

Published: July 29, 2023

Neuropsychiatric disorders including Alzheimer’s disease (AD) may cause gut inflammation and dysbiosis. Gut inflammation-suppressing probiotics alleviate neuropsychiatric disorders. Herein, to understand whether anti-inflammatory Lactobacillus mucosae NK41 Bifidobacterium longum NK46, which suppressed tumor necrosis factor (TNF)-α expression in lipopolysaccharide (LPS)-stimulated macrophages, could cognitive impairment, we first examined their effects on function, inflammation, microbiota composition 5xFAD-transgenic mice. Oral administration of or NK46 decreased impairment-like behaviors, hippocampal amyloid-β (Aβ), TNF-α interleukin (IL)-1β expression, NF-κB+Iba1+ cell population, Aβ accumulation, while brain-derived neurotropic (BDNF) IL-10 BDNF+NeuN+ population increased. They also IL-1β NF-κB+CD11c+ the colon. reduced fecal blood LPS levels Proteobacteria Verrucomicrobia populations (including Akkkermansiaceae), are positively associated with negatively correlated BDNF level. However, they increased Odoribactericeae, level ratio. The combination (4:1, NKc), potently inhibited LPS-stimulated additively alleviated behaviors aged NKc mice, decreased. colon feces. These findings suggest that bacteria its product be closely connected occurrence impairment neuroinflammation can by inducing NF-κB-suppressed suppressing LPS-producing bacteria.

Language: Английский

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Pseudostellaria heterophylla polysaccharide mitigates Alzheimer's-like pathology via regulating the microbiota-gut-brain axis in 5 × FAD mice

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 270, P. 132372 - 132372

Published: May 14, 2024

Language: Английский

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The NF-κB Pathway: Key Players in neurocognitive functions and related disorders

European Journal of Pharmacology, Journal Year: 2024, Volume and Issue: 984, P. 177038 - 177038

Published: Oct. 5, 2024

Language: Английский

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Gut microbiota in centenarians: A potential metabolic and aging regulator in the study of extreme longevity

Aging Medicine, Journal Year: 2024, Volume and Issue: 7(3), P. 406 - 413

Published: June 1, 2024

Centenarians, those aged 100 years or older, are considered the most successful biological aging model in humans. This population is commonly characterized by a low prevalence of chronic diseases, with favorable maintenance functionality and independence, thus determining health phenotype aging. There many factors usually associated extreme longevity: genetics, lifestyles, diet, among others. However, it likely multifactorial condition where protective contribute individually to some extent. The gut microbiota (GM) has emerged as potential factor establishment that allows for longevity, seen centenarians. To understand possible impact generated GM, its changes, probable causes aging, aim this review was synthesize evidence on role GM achieving using relationship

Language: Английский

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DHA Supplementation and Infant Brain Development: Role of Gut Microbiome

Nutrition Research, Journal Year: 2024, Volume and Issue: 131, P. 1 - 13

Published: Sept. 7, 2024

Language: Английский

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Asiaticoside improves depressive-like behavior in mice with chronic unpredictable mild stress through modulation of the gut microbiota

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: Oct. 18, 2024

Background Asiaticoside, the main active ingredient of Centella asiatica, is a pentacyclic triterpenoid compound. Previous studies have suggested that asiaticoside possesses neuroprotective and anti-depressive properties, however, mechanism its anti-depressant action not fully understood. In recent years, growing body research on anti-depressants has focused microbiota-gut-brain axis, we noted disruption gut microbial community structure diversity can induce or exacerbate depression, which plays key role in regulation depression. Methods Behavioral experiments were conducted to detect depression-like behavior mice through sucrose preference, forced swimming, open field tests. Additionally, composition short-chain fatty acid (SCFA) levels mouse feces analyzed 16S rRNA sequencing gas chromatography-mass spectrometry (GC-MS). Hippocampal brain-derived neurotrophic factor (BDNF) 5-hydroxytryptamine receptor 1A (5-HT1A) expression was assessed by western blotting. Changes serum inflammatory factors, neurotransmitters, hormones measured using ELISA. Results This study revealed oral administration significantly improved chronic unpredictable mild stress (CUMS) mice. It partially restored CUMS mice, altered SCFA metabolism, regulated hypothalamic–pituitary–adrenal axis (HPA axis) levels, upregulated BDNF 5-HT1A protein expression, increased serotonin (5-hydroxytryptamine, 5-HT) concentration. These findings reveal exerts antidepressant effects via axis. Conclusions results model.

Language: Английский

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