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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Microbiota-derived metabolites as drivers of gut–brain communication

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

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Transforming the understanding of brain immunity

Science, Journal Year: 2023, Volume and Issue: 380(6640)

Published: April 6, 2023

Contemporary studies have completely changed the view of brain immunity from envisioning as isolated and inaccessible to peripheral immune cells an organ in close physical functional communication with system for its maintenance, function, repair. Circulating reside special niches brain's borders, choroid plexus, meninges, perivascular spaces, which they patrol sense a remote manner. These niches, together meningeal lymphatic skull microchannels, provide multiple routes interaction between system, addition blood vasculature. In this Review, we describe current ideas about their implications aging, diseases, immune-based therapeutic approaches.

Language: Английский

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Intestinal mucus and their glycans: A habitat for thriving microbiota

Cell Host & Microbe, Journal Year: 2023, Volume and Issue: 31(7), P. 1087 - 1100

Published: July 1, 2023

The colon mucus layer is organized with an inner that impenetrable to bacteria and outer expanded allow microbiota colonization. A major component of MUC2, a glycoprotein extensively decorated, especially O-glycans. In the intestine, goblet cells are specialized in controlling glycosylation making mucus. Some members known encode multiple proteins predicted bind and/or cleave mucin glycans. interactions between commensal host mucins drive intestinal colonization, while at same time, can utilize glycans on affect colonic properties. This review will examine this interaction microbes discuss how interplay affects health disease.

Language: Английский

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Microbial metabolite enhances immunotherapy efficacy by modulating T cell stemness in pan-cancer

Cell, Journal Year: 2024, Volume and Issue: 187(7), P. 1651 - 1665.e21

Published: March 1, 2024

Language: Английский

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The microbiota–gut–brain axis and neurodevelopmental disorders

Protein & Cell, Journal Year: 2023, Volume and Issue: 14(10), P. 762 - 775

Published: May 11, 2023

Abstract The gut microbiota has been found to interact with the brain through microbiota–gut–brain axis, regulating various physiological processes. In recent years, impacts of on neurodevelopment this axis have increasingly appreciated. is commonly considered regulate three pathways, immune pathway, neuronal and endocrine/systemic overlaps crosstalks in between. Accumulating studies identified role neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity Rett Syndrome. Numerous researchers examined pathophysiological mechanisms influenced by (NDDs). This review aims provide a comprehensive overview advancements research pertaining microbiota-gut-brain NDDs. Furthermore, we analyzed both current state progress discuss future perspectives field.

Language: Английский

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Gut Microbiome–Brain Alliance: A Landscape View into Mental and Gastrointestinal Health and Disorders

ACS Chemical Neuroscience, Journal Year: 2023, Volume and Issue: 14(10), P. 1717 - 1763

Published: May 8, 2023

Gut microbiota includes a vast collection of microorganisms residing within the gastrointestinal tract. It is broadly recognized that gut and brain are in constant bidirectional communication, which its metabolic production major component, form so-called microbiome–brain axis. Disturbances homeostasis caused by imbalance their functional composition activities, known as dysbiosis, cause dysregulation these pathways trigger changes blood–brain barrier permeability, thereby causing pathological malfunctions, including neurological disorders. In turn, can affect structure function through autonomic nervous system regulating motility, intestinal transit secretion, permeability. Here, we examine data from CAS Content Collection, largest published scientific information, analyze publication landscape recent research. We review advances knowledge related to human microbiome, complexity functionality, communication with central system, effect axis on mental health. discuss correlations between various diseases, specifically also explore metabolites regard impact associated diseases. Finally, assess clinical applications gut-microbiota-related substances development pipelines. hope this serve useful resource understanding current emerging field an effort further solving remaining challenges fulfilling potential.

Language: Английский

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A Review of Gut Microbiota‐Derived Metabolites in Tumor Progression and Cancer Therapy

Advanced Science, Journal Year: 2023, Volume and Issue: 10(15)

Published: March 23, 2023

Abstract Gut microbiota‐derived metabolites are key hubs connecting the gut microbiome and cancer progression, primarily by remodeling tumor microenvironment regulating signaling pathways in cells multiple immune cells. The use of microbial radiotherapy chemotherapy mitigates severe side effects from treatment improves efficacy treatment. Immunotherapy combined with effectively activates system to kill tumors overcomes drug resistance. Consequently, various novel strategies have been developed modulate metabolites. Manipulation genes involved metabolism using synthetic biology approaches directly affects levels metabolites, while fecal transplantation phage affect altering composition microbiome. However, some harbor paradoxical functions depending on context (e.g., type cancer). Furthermore, metabolic microorganisms certain anticancer drugs such as irinotecan gemcitabine, render ineffective or exacerbate their adverse effects. Therefore, a personalized comprehensive consideration patient's condition is required when employing treat cancer. purpose this review summarize correlation between cancer, provide fresh ideas for future scientific research.

Language: Английский

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Gut microbiota bridges dietary nutrients and host immunity

Science China Life Sciences, Journal Year: 2023, Volume and Issue: 66(11), P. 2466 - 2514

Published: June 5, 2023

Language: Английский

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Neuroinflammation: An astrocyte perspective

Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(721)

Published: Nov. 8, 2023

Astrocytes are abundant glial cells in the central nervous system (CNS) that play active roles health and disease. Recent technologies have uncovered functional heterogeneity of astrocytes their extensive interactions with other cell types CNS. In this Review, we highlight intricate between astrocytes, CNS-resident cells, CNS-infiltrating as well potential therapeutic value context inflammation neurodegeneration.

Language: Английский

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