Atlas of gut microbe-derived products from aromatic amino acids and risk of cardiovascular morbidity and mortality

European Heart Journal, Journal Year: 2023, Volume and Issue: 44(32), P. 3085 - 3096

Published: June 21, 2023

Abstract Aims Precision microbiome modulation as a novel treatment strategy is rapidly evolving and sought goal. The aim of this study to determine relationships among systemic gut microbial metabolite levels incident cardiovascular disease risks identify pathways possible targets for personalized therapeutic interventions. Methods results Stable isotope dilution mass spectrometry methods quantitatively measure aromatic amino acids their metabolites were used examine sequential subjects undergoing elective diagnostic cardiac evaluation in two independent cohorts with longitudinal outcome data [US (n = 4000) EU 833) cohorts]. It was also plasma from humans mice before vs. after cocktail poorly absorbed antibiotics suppress microbiota. Multiple acid-derived that originate, at least part, bacteria are associated (3-year) major adverse event (MACE) (myocardial infarction, stroke, or death) all-cause mortality traditional risk factors. Key microbiota-derived MACE poorer survival include: (i) phenylacetyl glutamine glycine (from phenylalanine); (ii) p-cresol tyrosine) yielding sulfate glucuronide; (iii) 4-OH-phenyllactic acid 4-OH-benzoic 4-OH-hippuric acid; (iv) indole tryptophan) glucuronide indoxyl sulfate; (v) indole-3-pyruvic indole-3-lactic indole-3-acetyl-glutamine, (vi) 5-OH-indole-3-acetic tryptophan). Conclusion microbiota-generated derived independently outcomes identified, thus will help focus future studies on gut-microbial metabolic outputs relevant host health.

Language: Английский

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Feeding gut microbes to nourish the brain: unravelling the diet–microbiota–gut–brain axis

Nature Metabolism, Journal Year: 2024, Volume and Issue: 6(8), P. 1454 - 1478

Published: Aug. 22, 2024

Language: Английский

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Gut bacteria–derived serotonin promotes immune tolerance in early life

Science Immunology, Journal Year: 2024, Volume and Issue: 9(93)

Published: March 15, 2024

The gut microbiota promotes immune system development in early life, but the interactions between metabolome and cells neonatal remain largely undefined. Here, we demonstrate that is uniquely enriched with neurotransmitters, including serotonin, specific bacteria directly produce serotonin while down-regulating monoamine oxidase A to limit breakdown. We found signals T increase intracellular indole-3-acetaldehdye inhibit mTOR activation, thereby promoting differentiation of regulatory cells, both ex vivo intestine. Oral gavage into mice resulted long-term cell-mediated antigen-specific tolerance toward dietary antigens commensal bacteria. Together, our study has uncovered an important role for availability identified a function shaping cell response promote life.

Language: Английский

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Fermented foods: Harnessing their potential to modulate the microbiota-gut-brain axis for mental health

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 158, P. 105562 - 105562

Published: Jan. 25, 2024

Over the past two decades, whole food supplementation strategies have been leveraged to target mental health. In addition, there has increasing attention on ability of gut microbes, so called psychobiotics, positively impact behaviour though microbiota-gut-brain axis. Fermented foods offer themselves as a combined microbiota modulating intervention. Indeed, they contain potentially beneficial microbial metabolites and other bioactives, which are being harnessed axis for positive benefits. This review highlights diverse nature fermented in terms raw materials used type fermentation employed, summarises their potential shape composition microbiota, brain communication pathways including immune system and, ultimately, modulate Throughout, we identify knowledge gaps challenges faced designing human studies investigating health-promoting individual or components thereof. Importantly, also suggest solutions that can advance understanding therapeutic merit

Language: Английский

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Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

MedComm, Journal Year: 2024, Volume and Issue: 5(3)

Published: March 1, 2024

Abstract Autism spectrum disorder (ASD) has become a common neurodevelopmental disorder. The heterogeneity of ASD poses great challenges for its research and clinical translation. On the basis reviewing ASD, this review systematically summarized current status progress pathogenesis, diagnostic markers, interventions ASD. We provided an overview molecular mechanisms identified by multi‐omics studies convergent mechanism in different genetic backgrounds. comorbidities, associated with important physiological metabolic abnormalities (i.e., inflammation, immunity, oxidative stress, mitochondrial dysfunction), gut microbial were reviewed. non‐targeted omics targeting markers also Moreover, we methods behavioral educational interventions, intervention related to technological devices, on medical potential drug targets. This highlighted application high‐throughput emphasized importance seeking homogeneity from exploring convergence disease mechanisms, biomarkers, approaches, proposes that taking into account individuality commonality may be key achieve accurate diagnosis treatment

Language: Английский

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Dysbiosis of the gut microbiota and its effect on α-synuclein and prion protein misfolding: consequences for neurodegeneration

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

Published: Feb. 16, 2024

Abnormal behavior of α-synuclein and prion proteins is the hallmark Parkinson’s disease (PD) illnesses, respectively, being complex neurological disorders. A primary cause protein aggregation, brain injury, cognitive loss in illnesses misfolding normal cellular (PrP C ) into an infectious form Sc ). Aggregation causes disruptions processes (PD), leading to dopamine-producing neurons motor symptoms. Alteration composition or activity gut microbes may weaken intestinal barrier make it possible for prions go from brain. The gut-brain axis linked neuroinflammation; metabolites produced by microbiota affect aggregation α-synuclein, regulate inflammation immunological responses, influence course neurotoxicity proteins, even if their targets are distinct proteins. This thorough analysis explores interactions that exist between neurodegenerative particularly involvement microbiota, a collection bacteria, archaea, fungi, viruses etc., various becoming increasingly recognized. microbiome influences neuroinflammation, neurotransmitter synthesis, mitochondrial function, integrity through axis, which contributes development progression disease. review delves molecular mechanisms underlie these relationships, emphasizing effects microbial such as bacterial lipopolysaccharides (LPS), short-chain fatty acids (SCFAs) regulating functioning. Additionally, looks at how environmental dietary decisions whether they could be risk factors illnesses. study concludes highlighting critical role plays It also provides promising direction future research treatment approaches. People afflicted difficult ailments find hope new preventive therapeutic approaches diseases better understood.

Language: Английский

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Maternal immune activation induces autism-like changes in behavior, neuroinflammatory profile and gut microbiota in mouse offspring of both sexes

Translational Psychiatry, Journal Year: 2022, Volume and Issue: 12(1)

Published: Sept. 14, 2022

Abstract Autism Spectrum Disorder (ASD) is a sex-biased neurodevelopmental disorder with male to female prevalence of 4:1, characterized by persistent deficits in social communication and interaction restricted-repetitive patterns behavior, interests or activities. Microbiota alterations as well signs neuroinflammation have been also reported ASD. The involvement immune dysregulation ASD further supported evidence suggesting that maternal activation (MIA), especially during early pregnancy, may be risk factor for present study was aimed at characterizing the effects MIA on gut microbiota mouse offspring considering impact two sexes. exhibited significant ASD-like behavioral (i.e., sociability sensorimotor gating, perseverative behaviors). analysis revealed changes specific microbial taxa recapitulated those seen children. In addition, molecular analyses indicated sex-related differences neuroinflammatory responses triggered MIA, more prominent effect cerebellum. Our data suggest both sexes should included experimental designs preclinical studies order identify mechanisms confer different vulnerability males females.

Language: Английский

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Extracellular ATP: A powerful inflammatory mediator in the central nervous system

Neuropharmacology, Journal Year: 2022, Volume and Issue: 224, P. 109333 - 109333

Published: Nov. 15, 2022

Nucleotides play a crucial role in extracellular signaling across species boundaries.All the three kingdoms of life (Bacteria, Archea and Eukariota) are responsive to ATP (eATP) many release this other nucleotides.Thus, eATP fulfills different functions, related danger-sensing or avoidance reactions.Basically all living organisms have evolved sensors for nucleotides with very affinity selectivity, thus conferring remarkable plasticity system.Likewise, intracellular transduction systems were associated during evolution receptors eATP.In mammalian evolution, control (iATP) homeostasis has been closely intertwined that Ca 2+ , whether milieu cytoplasm, establishing an inverse reciprocal relationship, i.e. high levels negligible eATP, while low concentrations.This relationship is messenger functions both molecules.Extracellular sensed by specific plasma membrane widely named P2 (P2Rs) which 17 subtypes known.This confers P2R signaling.The central nervous system (CNS) privileged site purinergic as brain cell types express P2Rs.Accruing evidence suggests addition participating synaptic transmission, also plays homeostatic fine tuning microglia, astroglia oligodendroglia responses.Drugs modulating concentration CNS likely be new frontier therapy neuroinflammation.

Language: Английский

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The systemic immune response in Parkinson’s disease: focus on the peripheral immune component

Trends in Neurosciences, Journal Year: 2023, Volume and Issue: 46(10), P. 863 - 878

Published: Aug. 17, 2023

Language: Английский

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Glymphatic System Pathology and Neuroinflammation as Two Risk Factors of Neurodegeneration

Cells, Journal Year: 2024, Volume and Issue: 13(3), P. 286 - 286

Published: Feb. 5, 2024

The key to the effective treatment of neurodegenerative disorders is a thorough understanding their pathomechanism. Neurodegeneration and neuroinflammation are mutually propelling brain processes. An impairment glymphatic system function in neurodegeneration contributes progression pathological question arises as how related. This review highlights direct indirect influence these two seemingly independent Protein aggregates, characteristic feature neurodegeneration, correlated with clearance neuroinflammation. Glial cells cannot be overlooked when considering neuroinflammatory Astrocytes essential for functioning play crucial role inflammatory responses central nervous system. It imperative acknowledge significance AQP4, protein that exhibits high degree polarization astrocytes AQP4 influences processes have not yet been clearly delineated. Another interesting issue gut–brain axis microbiome, which potentially impact discussed A discussion correlation between may contribute exploring pathomechanism neurodegeneration.

Language: Английский

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