The Gut Microbiome-Neuroglia Axis: Implications for Brain Health, Inflammation, and Disease DOI Creative Commons
Josué Camberos-Barraza, Alma Marlene Guadrón‐Llanos, Alberto K. De la Herrán-Arita

et al.

Neuroglia, Journal Year: 2024, Volume and Issue: 5(3), P. 254 - 273

Published: Aug. 1, 2024

The human central nervous system is convolutedly connected to the gut microbiome, a diverse community of microorganisms residing in gastrointestinal tract. Recent research has highlighted bidirectional communication between microbiome and neuroglial cells, which include astrocytes, microglia, oligodendrocytes, ependymal cells. These cells are essential for maintaining CNS homeostasis, supporting neuronal function, responding pathological conditions. This review examines interactions neuroglia, emphasizing their critical roles brain health development neurological disorders. Dysbiosis, or imbalance been associated with various psychiatric conditions, such as autism spectrum disorder, anxiety, depression, neurodegenerative diseases like Alzheimer’s Parkinson’s. influences function through microbial metabolites, immune modulation, neuroinflammatory responses. Understanding these paves way new therapeutic targets strategies preventing treating scoping aims highlight mechanisms microbiome-neuroglia axis its potential target.

Language: Английский

Oxidative and Excitatory Neurotoxic Stresses in CRISPR/Cas9-Induced Kynurenine Aminotransferase Knockout Mice: A Novel Model for Despair-Based Depression and Post-Traumatic Stress Disorder DOI Creative Commons
Ágnes Szabó, Zsolt Galla, Eleonóra Spekker

et al.

Frontiers in Bioscience-Landmark, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 20, 2025

Backgrounds: Memory and emotion are especially vulnerable to psychiatric disorders such as post-traumatic stress disorder (PTSD), which is linked disruptions in serotonin (5-HT) metabolism. Over 90% of the 5-HT precursor tryptophan (Trp) metabolized via Trp-kynurenine (KYN) metabolic pathway, generates a variety bioactive molecules. Dysregulation KYN metabolism, particularly low levels kynurenic acid (KYNA), appears be neuropsychiatric disorders. The majority KYNA produced by aadat (kat2) gene-encoded mitochondrial kynurenine aminotransferase (KAT) isotype 2. Little known about consequences deleting enzyme gene. Methods: In CRISPR/Cas9-induced knockout (kat2-/-) mice, we examined effects on emotion, memory, motor function, Trp its metabolite levels, activities plasma urine 8-week-old males compared wild-type mice. Results: Transgenic mice showed more depressive-like behaviors forced swim test, but not tail suspension, anxiety, or memory tests. They also had fewer center field corner entries, shorter walking distances, jumping counts open test. Plasma generally consistent with those urine: antioxidant KYNs, 5-hydroxyindoleacetic acid, indole-3-acetic were lower; KATs, kynureninase, monoamine oxidase/aldehyde dehydrogenase lower, 3-monooxygenase was higher; oxidative excitotoxicity indices higher. displayed depression-like behavior learned helplessness model, emotional indifference, deficits, coupled decrease KYNA, shift metabolism toward KYN-3-hydroxykynurenine partial gut microbial Trp-indole pathway metabolite. Conclusions: This first evidence that gene induces uniquely experiences despair, appear associated excitatory neurotoxic stresses. may lead development double-hit preclinical model despair-based depression, better understanding these complex conditions, effective therapeutic strategies elucidating relationship between PTSD pathogenesis.

Language: Английский

Citations

2
Bioorthogonal Labeling and Enrichment of Histone Monoaminylation Reveal Its Accumulation and Regulatory Function in Cancer Cell Chromatin DOI
Nan Zhang, Jinghua Wu, Farzana Hossain

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(24), P. 16714 - 16720

Published: June 7, 2024

Histone monoaminylation (

Language: Английский

Citations

9
Modulation of the Neuro–Cancer Connection by Metabolites of Gut Microbiota DOI Creative Commons
Alice Njolke Mafe, Dietrich Büsselberg

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 270 - 270

Published: Feb. 12, 2025

The gut-brain-cancer axis represents a novel and intricate connection between the gut microbiota, neurobiology, cancer progression. Recent advances have accentuated significant role of microbiota metabolites in modulating systemic processes that influence both brain health tumorigenesis. This paper explores emerging concept metabolite-mediated modulation within connection, focusing on key such as short-chain fatty acids (SCFAs), tryptophan derivatives, secondary bile acids, lipopolysaccharides (LPS). While microbiota's impact immune regulation, neuroinflammation, tumor development is well established, gaps remain grasping how specific contribute to neuro-cancer interactions. We discuss with potential implications for neurobiology cancer, indoles polyamines, which yet be extensively studied. Furthermore, we review preclinical clinical evidence linking dysbiosis, altered metabolite profiles, tumors, showcasing limitations research gaps, particularly human longitudinal studies. Case studies investigating microbiota-based interventions, including dietary changes, fecal transplantation, probiotics, demonstrate promise but also indicate hurdles translating these findings therapies. concludes call standardized multi-omics approaches bi-directional frameworks integrating microbiome, neuroscience, oncology develop personalized therapeutic strategies patients.

Language: Английский

Citations

1
Exploring effects of gut microbiota on tertiary lymphoid structure formation for tumor immunotherapy DOI Creative Commons
Yuqing Liu,

Fan Li,

Juanjuan Wang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: March 7, 2025

Anti-tumor immunity, including innate and adaptive immunity is critical in inhibiting tumorigenesis development of tumor. The needs specific lymph organs such as tertiary lymphoid structures (TLSs), which are highly correlated with improved survival outcomes many cancers. In recent years, increasing attention on the TLS tumor microenvironment, TLSs have emerged a novel target for anti-tumor therapy. Excitingly, studies shown contribution to immune responses. However, it unclear how form more effectively defense against through formation. Recent that inflammation plays role Interestingly, also found gut microbiota can regulate occurrence inflammation. Therefore, we here summarize potential effects microbiota- mediated or immunosuppression formation environments. Meanwhile, this review explores manipulate mature regulating microbiota/metabolites associated signal pathways potentially lead next-generation cancer immunotherapy.

Language: Английский

Citations

1
The tryptophan metabolic pathway of the microbiome and host cells in health and disease DOI Creative Commons
Kentaro Miyamoto, Tomohisa Sujino, Takanori Kanai∥

et al.

International Immunology, Journal Year: 2024, Volume and Issue: unknown

Published: June 13, 2024

Abstract The intricate and dynamic tryptophan (Trp) metabolic pathway in both the microbiome host cells highlights its profound implications for health disease. This involves complex interactions between cellular bacteria processes, producing bioactive compounds such as 5-hydroxytryptamine (5-HT) kynurenine derivatives. Immune responses to Trp metabolites through specific receptors have been explored, highlighting role of aryl hydrocarbon receptor inflammation modulation. Dysregulation this is implicated various diseases, Alzheimer’s Parkinson’s mood disorders, neuronal autoimmune diseases multiple sclerosis (MS), cancer. In article, we describe impact 5-HT, Trp, indole, on Furthermore, review microbiome-derived that affect immune contribute maintaining homeostasis, especially an experimental encephalitis model MS.

Language: Английский

Citations

8
Impaired Kynurenine Pathway in Inflammatory Bowel Disease DOI Open Access
Esra Paydaş Hataysal, Muslu Kazım Körez, Eray Metin Güler

et al.

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(20), P. 6147 - 6147

Published: Oct. 15, 2024

: Inflammatory bowel diseases primarily encompass Crohn's disease and ulcerative colitis. Insufficient levels of tryptophan cause an imbalance in the gut microbiota, leading to inflammation gastrointestinal tract. The main catabolic pathway is kynurenine pathway. Our study aims evaluate serum tryptophan, pathway, oxidative stress parameters, including total oxidant status antioxidant capacity, patients with

Language: Английский

Citations

6
Bioorthogonal labeling and enrichment of histone monoaminylation reveal its accumulation and regulatory function in cancer cell chromatin DOI Open Access
Nan Zhang, Jinghua Wu, Farzana Hossain

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 20, 2024

Abstract Histone monoaminylation ( i . e ., serotonylation and dopaminylation) is an emerging category of epigenetic mark occurring on the fifth glutamine (Q5) residue H3 N-terminal tail, which plays significant roles in gene transcription. Current analysis histone mainly based site-specific antibodies mass spectrometry, either lacks high resolution or time-consuming. In this study, we report development chemical probes for bioorthogonal labeling enrichment dopaminylation. These were successfully applied vitro biochemical assays, cells, tissue samples. The monoaminylated histones by further confirmed crosstalk between H3Q5 H3K4 methylation. Finally, combining ex vivo analyses developed probes, have shown that both dopaminylation are highly enriched tumor tissues overexpress transglutaminase 2 (TGM2) regulate three-dimensional architecture cellular chromatin. TOC

Language: Английский

Citations

5
Intestinal Barrier, Immunity and Microbiome: Partners in the Depression Crime DOI Creative Commons
Eva M. Medina‐Rodríguez, José Martı́nez-Raga, Yolanda Sanz

et al.

Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 76(5), P. 956 - 969

Published: July 31, 2024

Depression is a highly prevalent disorder and leading cause of disability worldwide. It has major impact on the affected individual society as whole. Regrettably, current available treatments for this condition are insufficient in many patients. In recent years, gut microbiome emerged promising alternative target treating preventing depressive disorders. However, microbes that form ecosystem do not act alone but part complicated network connecting brain influences our mood. Host cells intimate contact with microbes, such epithelial forming barrier immune their vicinity, play key role process. These continuously shape responses to maintain healthy communication between host. article, we review how interplay among cells, system, mediates gut-brain influence We also discuss advances knowledge mechanisms underlying axis could contribute addressing depression.

Significance Statement

This does aim systematically describe intestinal might be beneficial or detrimental have adopted novel point view by focusing potential crosstalk environment control pathways targeted well defined individually tailored dietary interventions, microbial metabolites ameliorate depression decrease its important social economic impact.

Language: Английский

Citations

5
Game of microbes: the battle within – gut microbiota and multiple sclerosis DOI Creative Commons

Ti-Ara Turner,

Peter Lehman,

Sudeep Ghimire

et al.

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: Aug. 8, 2024

Multiple sclerosis (MS) is a chronic and progressive autoimmune disease of the central nervous system (CNS), with both genetic environmental factors contributing to pathobiology disease. While human leukocyte antigen (HLA) genes have emerged as strongest factor, consensus on risk are lacking. Recently, trillions microbes residing in our gut (microbiome) potential factor linked MS PwMS show microbial dysbiosis (altered microbiome). Thus, there has been strong emphasis understanding (host environmental) regulating composition microbiota mechanism(s) through which contribute disease, especially immune modulation. A better these interactions will help harness enormous therapeutic approach treating MS.

Language: Английский

Citations

5
The Influence of Cecal Microbiota Transplantation on Chicken Injurious Behavior: Perspective in Human Neuropsychiatric Research DOI Creative Commons
Yuechi Fu, H.W. Cheng

Biomolecules, Journal Year: 2024, Volume and Issue: 14(8), P. 1017 - 1017

Published: Aug. 16, 2024

Numerous studies have evidenced that neuropsychiatric disorders (mental illness and emotional disturbances) with aggression (or violence) pose a significant challenge to public health contribute substantial economic burden worldwide. Especially, social disorganization inequality) associated childhood adversity has long-lasting effects on mental health, increasing the risk of developing disorders. Intestinal bacteria, functionally as an endocrine organ second brain, release various immunomodulators bioactive compounds directly or indirectly regulating host’s physiological behavioral homeostasis. Under challenges, stress-induced dysbiosis increases gut permeability causes serial reactions: releasing neurotoxic compounds, leading neuroinflammation neuronal injury, eventually aggressive, violent, impulsive behavior in humans animals via complex bidirectional communication microbiota–gut–brain (MGB) axis. The dysregulation MGB axis also been recognized one reasons for prevalence injurious behaviors (feather pecking, aggression, cannibalistic pecking) chickens. However, existing knowledge preventing treating these both chickens is not well understood. In previous studies, we developed non-mammal model abnormal investigation by rationalizing microbiota Based our earlier success, perspective article outlines possibility reducing through modifying cecal transplantation, potential providing biotherapeutic rationale among individuals restoring diversity function.

Language: Английский

Citations

4