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

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Feb. 16, 2024

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

Language: Английский

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Gut microbial characteristical comparison reveals potential anti-aging function of Dubosiella newyorkensis in mice

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Jan. 31, 2023

Introduction Previous study has indicated Dubosiella newyorkensis may act as a potential probiotic in age-related diseases. However, its detailed role aging not yet been promulgated. This aimed to explore the anti-aging of by comparing effect resveratrol young and old mice. Method Measurement intestinal aging-related factors colon serum, vascular endothelial function-related serum were performed enzyme-linked immunosorbent assay (ELISA). Gut microbial analysis contents identified 16S rRNA gene sequencing. Results The on reducing malondialdehyde (MDA) increasing superoxide dismutase (SOD) aged mice greater than that resveratrol. While nitric oxide (NO) level was less resveratrol, reduction growth factor (VEGF) pentosidine (PTD) better In mice, promoted an increase beneficial genus Lactobacillus, Bifidobacterium Ileibacterium effectively compared with treatment. Bifidobacterium, Akkermansia, Staphylococcus, Verrucomicrobiota expression Both showed same results for remaining markers, including changes gut composition predictions function. Conclusion similar functions even be more effective oxidative stress, improving function, redistributing microbiota. research provides innovative strategy improve aging.

Language: Английский

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Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Feb. 27, 2024

The aetiologies and origins of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS) Huntington's (HD), are complex multifaceted. A growing body evidence suggests that the gut microbiome plays crucial roles in development progression diseases. Clinicians have come to realize therapeutics targeting potential halt This narrative review examines alterations AD, PD, ALS HD, highlighting close relationship between brain Processes mediate microbiome-brain communication including immunological, vagus nerve circulatory pathways, evaluated. Furthermore, we summarize for diseases modify its metabolites, diets, probiotics prebiotics, microbial antibacterials faecal transplantation. Finally, current challenges future directions discussed.

Language: Английский

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Outer Membrane Vesicles Released from Garlic Exosome‐like Nanoparticles (GaELNs) Train Gut Bacteria that Reverses Type 2 Diabetes via the Gut‐Brain Axis

Small, Journal Year: 2024, Volume and Issue: 20(20)

Published: Jan. 15, 2024

Gut microbiota function has numerous effects on humans and the diet consume emerged as a pivotal determinant of gut function. Here, new concept that can be trained by diet-derived exosome-like nanoparticles (ELNs) to release healthy outer membrane vesicles (OMVs) is introduced. Specifically, OMVs released from garlic ELN (GaELNs) human Akkermansia muciniphila (A. muciniphila) reverse high-fat diet-induced type 2 diabetes (T2DM) in mice. Oral administration GaELNs A. traffick brain where they are taken up microglial cells, resulting inhibition inflammation. treatment increases levels OMV Amuc-1100, P9, phosphatidylcholines. Increasing Amuc-1100 P9 leads increasing GLP-1 plasma level. phosphatidylcholines required for cGas STING-mediated inflammation GLP-1R crosstalk with insulin pathway expression Insulin Receptor Substrate (IRS1 IRS2) targeted cells. These findings reveal molecular mechanism whereby plant nanoparticle-trained bacteria regulate genes expressed brain, have implications dysfunction caused metabolic syndrome.

Language: Английский

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Plant-nanoparticles enhance anti-PD-L1 efficacy by shaping human commensal microbiota metabolites

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 3, 2025

Abstract Diet has emerged as a key impact factor for gut microbiota function. However, the complexity of dietary components makes it difficult to predict specific outcomes. Here we investigate plant-derived nanoparticles (PNP) on and metabolites in context cancer immunotherapy with humanized gnotobiotic mouse model. Specifically, show that ginger-derived exosome-like nanoparticle (GELN) preferentially taken up by Lachnospiraceae Lactobacillaceae mediated digalactosyldiacylglycerol (DGDG) glycine, respectively. We further demonstrate GELN aly-miR159a-3p enhances anti-PD-L1 therapy melanoma inhibiting expression recipient bacterial phospholipase C (PLC) increases accumulation docosahexaenoic acid (DHA). An increased level circulating DHA inhibits PD-L1 tumor cells binding promoter subsequently prevents c-myc-initiated transcription PD-L1. Colonization germ-free male mice bacteria from non-responding patients supplemented efficacy compared controls. Our findings reveal previously unknown mechanistic PNP human modulating metabolic pathways.

Language: Английский

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Microbiota-immune-brain interactions: A lifespan perspective

Current Opinion in Neurobiology, Journal Year: 2022, Volume and Issue: 78, P. 102652 - 102652

Published: Dec. 1, 2022

There is growing appreciation of key roles the gut microbiota in maintaining homeostasis and influencing brain behaviour at critical windows across lifespan. Mounting evidence suggests that communication between could be to understanding multiple neuropsychiatric disorders, with immune system coming forefront as an important mechanistic mediator. Throughout lifespan, exchanges continuous reciprocal signals central nervous system. Intestinal microbial cues alter mediators consequences for host neurophysiology behaviour. Several factors challenge composition, which response release molecules neuro- immuno-active potential are crucial adequate neuro-immune interactions. In this review, contributing upkeep fine balance health disease these systems discussed, we elucidate implications inputs on

Language: Английский

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Leucine-Restricted Diet Ameliorates Obesity-Linked Cognitive Deficits: Involvement of the Microbiota–Gut–Brain Axis

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(24), P. 9404 - 9418

Published: June 12, 2023

Leucine restriction (LR) improves insulin resistance and promotes white adipose tissue browning. However, the effect of LR on obesity-associated cognitive impairment remains unclear. The present study found that an 8-week dramatically improved high-fat diet (HFD)-induced decline by preventing synaptic dysfunction, increasing expressions neurotrophic factors, inhibiting neuroinflammation in memory-related brain regions. Moreover, notably reshaped structure gut microbiota, which was manifested downregulating Firmicutes/Bacteroidetes ratio, reducing relative abundance inflammation-related bacteria including Acetatifactor, Helicobacter, Mucispirillum, Oscillibacter but short-chain fatty acid (SCFA)-producing bacterial genera Alistipes, Allobaculum, Odoribacter, Olsenella. Notably, HFD-caused SCFA reduction, barrier damage, LPS leakage were recovered LR. Our findings suggested could serve as effective approach to attenuate obesity-induced deficits, may be achieved balancing microbiota homeostasis enhancing production.

Language: Английский

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Association between gut microbiota and glioblastoma: a Mendelian randomization study

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

Published: Jan. 4, 2024

Background: Glioblastoma (GBM) is the most prevalent malignant brain tumor, significantly impacting physical and mental wellbeing of patients. Several studies have demonstrated a close association between gut microbiota development GBM. In this investigation, Mendelian randomization (MR) was employed to rigorously evaluate potential causal relationship Methods: We utilized summary statistics derived from genome-wide (GWAS) encompassing 211 The GBM scrutinized using Inverse Variance Weighted (IVW), MR-Egger, Median (WM) methods. Cochrane’s Q statistic conduct heterogeneity test. MR-Pleiotropic Residuals Outliers (MR-PRESSO) were applied identify eliminate SNPs with horizontal pleiotropic outliers. Additionally, Reverse MR assess pertinent microbiota. Results: study estimates suggest that nine remain stable, considering sensitivity Among these, family.Peptostreptococcaceae genus.Eubacterium brachy group associated an increased risk GBM, whereas family.Ruminococcaceae , genus.Anaerostipes genus.Faecalibacterium genus.LachnospiraceaeUCG004 genus.Phascolarctobacterium genus.Prevotella7 genus.Streptococcus reduced Following Benjamini Hochberg (BH) correction, (OR = 0.04, 95% CI: 0.01–0.19, FDR 0.003) identified as playing protective role against Conclusion: This groundbreaking first demonstrate modulation family_Ruminococcaceae for treatment holds considerable clinical significance.

Language: Английский

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The role of microglia immunometabolism in neurodegeneration: Focus on molecular determinants and metabolic intermediates of metabolic reprogramming

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 153, P. 113412 - 113412

Published: July 14, 2022

Microglia, resident macrophages that act as the brain's innate immune cells, play a key role in initiating defense response to infection or neuroinflammation of host. Once broad spectrum dangers is confronted, microglia get triggered and transform their against stimuli. Recent studies have shown remarkable metabolic changes present activated affect function. Given important progression neurodegeneration widely recognized, it crucial know whether reprogramming also presents how this may influence progression. This paper provides an overview microglia, major pathways involved recent advances five neurodegenerative diseases aging (NDAs), including Alzheimer's disease (AD), Parkinson's (PD), multiple sclerosis (MS), amyotrophic lateral (ALS), frontotemporal dementia (FTD), etc. And then we elucidated impacts on neurodegeneration. Furthermore, growing evidence suggests microbiota-derived metabolites, acetate, N6-carboxymethyllysine (CML), isoamylamine (IAA), regulate functions cellular homeostasis. We shed light topic concluded these metabolites are potential therapeutic targets for NDAs.

Language: Английский

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Investigating the causal impact of gut microbiota on glioblastoma: a bidirectional Mendelian randomization study

BMC Genomics, Journal Year: 2023, Volume and Issue: 24(1)

Published: Dec. 18, 2023

Abstract Background Currently, the influence of microbiota on occurrence, progression, and treatment cancer is a topic considerable research interest. Therefore, based theory gut-brain axis proved by previous studies, our objective was to uncover causal relationship between glioblastoma gut microbiome using Mendelian randomization analysis. Methods We conducted bidirectional study summary statistics derived from MiBioGen consortium, largest database microbiota. Summary for were obtained IEU OpenGWAS project, which included 91 cases 218,701 controls. assessed presence heterogeneity horizontal pleiotropy in analyzed data. primarily employed inverse variance weighting method investigate after excluding pleiotropy. Four other analysis methods as supplementary. Excluding abnormal results leave-one-out sensitivity Finally, reverse performed. Results genus-level taxa one family-level exhibited associations with glioblastoma. And these shown three taxa. However, Prevotella7(Forward, P =0.006, OR=0.34, 95%CI:0.158-0.732; Reverse, =0.004, OR=0.972, 95%CI:0.953-0.991) randomization. Conclusions In this study, we identified five species additional randomized controlled trials are required clarify impact reveal its precise mechanisms.

Language: Английский

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