Alzheimer s Research & Therapy, Journal Year: 2023, Volume and Issue: 15(1)
Published: May 31, 2023
Increasing evidence links the gut microbiota (GM) to Alzheimer's disease (AD) but mechanisms through which bacteria influence brain are still unclear. This study tests hypothesis that GM and mediators of microbiota-gut-brain axis (MGBA) associated with amyloid cascade in sporadic AD.
Language: Английский
Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)
Published: July 12, 2023
Abstract Studies in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and Amyotrophic lateral sclerosis, Huntington’s so on, have suggested that inflammation is not only a result of neurodegeneration but also crucial player this process. Protein aggregates which are very common pathological phenomenon can induce neuroinflammation further aggravates protein aggregation neurodegeneration. Actually, even happens earlier than aggregation. Neuroinflammation induced by genetic variations CNS cells or peripheral immune may deposition some susceptible population. Numerous signaling pathways range been to be involved the pathogenesis neurodegeneration, although they still far from being completely understood. Due limited success traditional treatment methods, blocking enhancing inflammatory considered promising strategies for therapy many them got exciting results animal models clinical trials. Some them, few, approved FDA usage. Here we comprehensively review factors affecting major pathogenicity sclerosis. We summarize current strategies, both clinic, diseases.
Language: Английский
Citations
545
Molecular and Cellular Endocrinology, Journal Year: 2022, Volume and Issue: 546, P. 111572 - 111572
Published: Jan. 20, 2022
The role of the intestinal microbiota as a regulator gut-brain axis signalling has risen to prominence in recent years. Understanding relationship between gut microbiota, metabolites it produces, and brain will be critical for subsequent development new therapeutic approaches, including identification novel psychobiotics. A key focus this regard have been short-chain fatty acids (SCFAs) produced by bacterial fermentation dietary fibre, which include butyrate, acetate, propionate. Ongoing research is focused on entry SCFAs into systemic circulation from lumen, their migration cerebral across blood barrier, potential exert acute chronic effects structure function. This review aims discuss our current mechanistic understanding direct indirect influence that function, behaviour physiology, inform future microbiota-targeted interventions disorders.
Language: Английский
Citations
299
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
Citations
237
International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(19), P. 11245 - 11245
Published: Sept. 24, 2022
Modulating the gut microbiome and its influence on human health is subject of intense research. The microbiota could be associated not only with gastroenterological diseases but also psychiatric disorders. importance factors such as stress, mode delivery, role probiotics, circadian clock system, diet, occupational environmental exposure in relationship between brain function through bidirectional communication, described "the microbiome-gut-brain axis", especially underlined. In this review, we discuss link intestinal host response involving different pathways nervous system (e.g., neurotransmitters, endocrine immunological mechanisms, or bacterial metabolites). We review alterations their results development disorders, including major depressive disorder (MDD), schizophrenia (SCZ), bipolar (BD), autism spectrum (ASD), attention-deficit hyperactivity (ADHD).
Language: Английский
Citations
233
eLife, Journal Year: 2021, Volume and Issue: 10
Published: April 13, 2021
Previous studies have identified a crucial role of the gut microbiome in modifying Alzheimer’s disease (AD) progression. However, mechanisms microbiome–brain interaction AD were so far unknown. Here, we identify microbiota-derived short chain fatty acids (SCFA) as microbial metabolites which promote Aβ deposition. Germ-free (GF) mice exhibit substantially reduced plaque load and markedly SCFA plasma concentrations; conversely, supplementation to GF increased levels conventionally colonized (specific pathogen-free [SPF]) animals SPF even further exacerbated load. This was accompanied by pronounced alterations microglial transcriptomic profile, including upregulation ApoE. Despite recruitment plaques upon supplementation, microglia contained less intracellular Aβ. Taken together, our results demonstrate that are critical mediators along gut-brain axis deposition likely via modulation phenotype.
Language: Английский
Citations
229
Molecular Neurodegeneration, Journal Year: 2022, Volume and Issue: 17(1)
Published: March 5, 2022
The implication of gut microbiota in the control brain functions health and disease is a novel, currently emerging concept. Accumulating data suggest that exert its action at least part by modulating neuroinflammation. Given link between neuroinflammatory changes neuronal activity, it plausible may affect indirectly impacting microglia, key player Indeed, increasing evidence suggests interplay microglia synaptic dysfunction involve microbiota, among other factors. In addition to these indirect microglia-dependent actions on has been recently recognized could also activity directly stimulation vagus nerve.
Language: Английский
Citations
202
Gut Microbes, Journal Year: 2022, Volume and Issue: 14(1)
Published: July 28, 2022
Alterations in the gut microbiota composition have been associated with a range of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. The microbes transform metabolize dietary- host-derived molecules generating diverse group metabolites local systemic effects. bi-directional communication between brain residing gut, so-called gut–brain axis, consists network immunological, neuronal, endocrine signaling pathways. Although full variety mechanisms crosstalk is yet to be established, existing data demonstrates that single metabolite or its derivatives are likely among key inductors within axis communication. However, more research needed understand molecular underlying how alter functions, examine if different interventional approaches targeting could used prevention treatment neurological disorders, as reviewed herein.Abbreviations:4-EPS 4-ethylphenylsulfate; 5-AVA(B) 5-aminovaleric acid (betaine); Aβ Amyloid beta protein; AhR Aryl hydrocarbon receptor; ASD Autism spectrum disorder; BBB Blood–brain barrier; BDNF Brain-derived neurotrophic factor; CNS Central nervous system; GABA ɣ-aminobutyric acid; GF Germ-free; MIA Maternal immune activation; SCFA Short-chain fatty 3M-4-TMAB 3-methyl-4-(trimethylammonio)butanoate; 4-TMAP 4-(trimethylammonio)pentanoate; TMA(O) Trimethylamine(-N-oxide); TUDCA Tauroursodeoxycholic ZO Zonula occludens proteins
Language: Английский
Citations
202
Microbiome, Journal Year: 2021, Volume and Issue: 9(1)
Published: Oct. 26, 2021
The intestinal microbiota plays an important role in regulating gastrointestinal (GI) physiology part through interactions with the enteric nervous system (ENS). Alterations gut microbiome frequently occur together disturbances neural control pathophysiological conditions. However, mechanisms by which regulates GI function and structure of ENS are incompletely understood. Using a mouse model antibiotic (Abx)-induced bacterial depletion, we sought to determine molecular microbial regulation integrity ENS. Spontaneous reconstitution Abx-depleted was used assess plasticity tract Microbiota-dependent neuronal survival neurogenesis were also assessed.Adult male female Abx-treated mice exhibited alterations function, including longer small intestine, slower transit time, increased carbachol-stimulated ion secretion, permeability. These accompanied loss neurons ileum proximal colon both submucosal myenteric plexuses. A reduction number glia only observed ileal plexus. Recovery restored stimulated leading increases neurons. Lipopolysaccharide (LPS) supplementation enhanced alongside but had no effect on recovery once Abx-induced established. In contrast, short-chain fatty acids (SCFA) able restore numbers after loss, demonstrating that SCFA stimulate vivo.Our results demonstrate for sex-independent manner. Moreover, is essential maintenance integrity, promoting neurogenesis. Molecular determinants microbiota, LPS SCFA, regulate survival, while stimulates Our data reveal new insights into could lead therapeutic developments treatment neuropathies. Video abstract.
Language: Английский
Citations
196
Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 12
Published: Jan. 6, 2022
Alzheimer’s disease (AD) is a devastating age-related neurodegenerative disorder with an alarming increasing prevalence. Except for the recently FDA-approved Aducanumab of which therapeutic effect not yet conclusively proven, only symptomatic medication that effective some AD patients available. In order to be able design more rational and treatments, our understanding mechanisms behind pathogenesis progression urgently needs improved. Over last years, it became increasingly clear peripheral inflammation one detrimental factors can contribute disease. Here, we discuss current how systemic intestinal (referred as gut-brain axis) inflammatory processes may affect brain pathology, specific focus on AD. Moreover, give comprehensive overview different preclinical well clinical studies link Inflammation initiation progression. Altogether, this review broadens pathology help in further research aiming identify novel targets.
Language: Английский
Citations
196
Science Translational Medicine, Journal Year: 2021, Volume and Issue: 13(615)
Published: Oct. 13, 2021
2-Deoxy-2-[18F]fluoro-d-glucose positron emission tomography (FDG-PET) is widely used to study cerebral glucose metabolism. Here, we investigated whether the FDG-PET signal directly influenced by microglial uptake in mouse models and patients with neurodegenerative diseases. Using a recently developed approach for cell sorting after FDG injection, found that, at cellular resolution, microglia displayed higher than neurons astrocytes. Alterations were responsible both decrease Trem2-deficient mice increase amyloidosis. Thus, opposite activation states determine differential uptake. Consistently, 12 Alzheimer’s disease 21 four-repeat tauopathies also exhibited positive association between activity as determined 18F-GE-180 18-kDa translocator protein PET (TSPO-PET) preserved brain regions, indicating that humans strongly activity. Our findings suggest are alterations diseases Microglial should therefore be considered when performing FDG-PET.
Language: Английский
Citations
178