Cracking Brain Diseases from Gut Microbes-Mediated Metabolites for Precise Treatment

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(10), P. 2974 - 2998

Published: Jan. 1, 2023

The gut-brain axis has been a subject of significant interest in recent years.Understanding the link between gut and brain is crucial for treatment disorders.Here, intricate components unique relationship microbiota-derived metabolites are explained detail.Additionally, association integrity blood-brain barrier health emphasized.Meanwhile, with their applications, challenges opportunities pathways on different disease focus discussed.The prospective strategy potential applies to treatments, such as Parkinson's Alzheimer's disease, proposed.This review provides broad perspective characteristics facilitate understand connection pave way development new medication delivery system metabolites.

Language: Английский

---

Microbiome–Gut–Mucosal–Immune–Brain Axis and Autism Spectrum Disorder (ASD): A Novel Proposal of the Role of the Gut Microbiome in ASD Aetiology

Behavioral Sciences, Journal Year: 2023, Volume and Issue: 13(7), P. 548 - 548

Published: June 30, 2023

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterised by deficits in social interaction and communication, as well restricted stereotyped interests. Due of the high prevalence gastrointestinal disorders individuals with ASD, researchers have investigated gut microbiota potential contributor to its aetiology. The relationship between microbiome, gut, brain (microbiome–gut–brain axis) has been acknowledged key factor modulating function behaviour, but connection aetiology ASD not understood. Recently, there increasing attention on immune system, neurological issues particularly relation loss specific species or decrease microbial diversity. It focuses how dysbiosis can affect permeability, metabolites ASD. However, very complete study suggests that consequence disease it practically no effect autistic manifestations. This review diversity microbiome–gut–brain axis development symptoms severity proposal novel role microbiome where ASD-related behaviour turn accentuates manifestations patients via feedback circuit.

Language: Английский

---

The “Connectivome Theory”: A New Model to Understand Autism Spectrum Disorders

Frontiers in Psychiatry, Journal Year: 2022, Volume and Issue: 12

Published: Feb. 7, 2022

The classical approach to autism spectrum disorders (ASD) is often limited considering their neuro-functional aspects. However, recent scientific literature has shown that ASDs also affect many body systems and apparatuses such as the immune system, sensory-motor gut-brain axis. connective tissue, a common thread linking all these structures, may have pathogenetic role in multisystem involvement of ASD. Depending on its different anatomical sites, tissue performs functions connection support; furthermore, it acts barrier between external internal environments, regulating interchange two performing immunological surveillance. shares close relationship with central nervous musculoskeletal system system. Alterations brain connectivity are various developmental disorders, including ASD, for this reason here we put forward hypothesis alterations physiological activity microglia could be implicated pathogenesis Also, muscle hypotonia likely clinically correlate an altered sensoriality and, fact, discomfort or early fatigue reported ASDs. Furthermore, patients ASD suffer from intestinal dysfunctions, malabsorption leaky gut syndrome, phenomena linked reduced connectivity. In addition, at cutaneous subcutaneous levels, show greater predisposition inflammatory events due lack adequate release anti-inflammatory mediators. Alveolar-capillary dysfunctions been observed most frequently interstitial inflammations, immune-mediated forms allergic asthma, bronchial hyper-reactivity. Therefore, autism, can result sensitivity environmental stimuli. following interpretative model, define “connectivome theory,” considers elements mesodermal origin located organs entails evaluation interpretation through highlighting somatic elements. We believe broader helpful more accurate analysis, able enrich clinical multidisciplinary personalized interventions.

Language: Английский

---

Transcriptional and epigenetic regulation of microglia in maintenance of brain homeostasis and neurodegeneration

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 15

Published: Jan. 9, 2023

The emerging role of microglia in brain homeostasis, neurodegeneration, and neurodevelopmental disorders has attracted considerable interest. In addition, recent developments microglial functions associated pathways have shed new light on their fundamental the immunological surveillance brain. Understanding interconnections between microglia, neurons, non-neuronal cells opened up additional avenues for research this evolving field. Furthermore, study at transcriptional epigenetic levels enhanced our knowledge these native immune cells. Moreover, exploring various facets biology will facilitate early detection, treatment, management neurological disorders. Consequently, present review aimed to provide comprehensive insight its influence development, disease, highlights as potential therapeutic targets neurodegenerative diseases.

Language: Английский

---

Gut Metabolites Acting on the Gut-Brain Axis: Regulating the Functional State of Microglia

Aging and Disease, Journal Year: 2023, Volume and Issue: 15(2), P. 480 - 480

Published: Aug. 3, 2023

The gut-brain axis is a communication channel that mediates complex interplay of intestinal flora with the neural, endocrine, and immune systems, linking gut brain functions. Gut metabolites, group small molecules produced or consumed by biochemical processes in gut, are involved central nervous system regulation via highly interconnected affecting microglia indirectly influencing structure directly function activity. Accordingly, pathological changes connected metabolite levels as well altered activity, which may contribute to process each neuroinflammatory condition. Here, we discuss mechanisms for instance, bile acids, short-chain fatty tryptophan regulate component axis, explore important roles metabolites from perspective microglia. At same time, highlight pathogenesis neurodegenerative diseases neurodevelopmental disorders. Understanding relationship between microglia, microbiota, neuroinflammation, disorders will help us identify new strategies treating neuropsychiatric

Language: Английский

---

Probiotic treatment causes sex-specific neuroprotection after traumatic brain injury in mice

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: April 2, 2024

Abstract Background Recent studies have shed light on the potential role of gut dysbiosis in shaping traumatic brain injury (TBI) outcomes. Changes levels and types Lactobacillus bacteria present might impact immune system disturbances, neuroinflammatory responses, anxiety depressive-like behaviors, compromised neuroprotection mechanisms triggered by TBI. Objective This study aimed to investigate effects a daily pan-probiotic (PP) mixture drinking water containing strains plantarum, L. reuteri, helveticus, fermentum, rhamnosus, gasseri , casei administered for either two or seven weeks before inducing TBI both male female mice. Methods Mice were subjected controlled cortical (CCI) injury. Short-chain fatty acids (SCFAs) analysis was performed metabolite measurements. The taxonomic profiles murine fecal samples evaluated using 16S rRNA V1-V3 sequencing analysis. Histological analyses used assess neuroinflammation changes post-TBI, while behavioral tests conducted evaluate sensorimotor cognitive functions. Results Our findings suggest that PP administration modulates diversity composition microbiome increases SCFAs sex-dependent manner. We also observed reduction lesion volume, cell death, microglial macrophage activation after treatment following Furthermore, PP-treated mice show motor function improvements decreases behaviors. Conclusion can mitigate ameliorate behavior deficits These results underscore probiotic interventions as viable therapeutic strategy address TBI-induced impairments, emphasizing need gender-specific approaches.

Language: Английский

---

Probiotics in autism spectrum disorder: Recent insights from animal models

Autism, Journal Year: 2024, Volume and Issue: 28(11), P. 2722 - 2737

Published: April 26, 2024

Autism spectrum disorder is a neurodevelopmental characterized by wide range of behavioral alterations, including impaired social interaction and repetitive behaviors. Numerous pharmacological interventions have been developed for autism disorder, often proving ineffective accompanied multitude side effects. The gut microbial alterations observed in individuals with elevated levels Bacteroidetes, Firmicutes, Proteobacteria, as well reduced Bifidobacterium, provide basis further investigation. Recent preclinical studies shown favorable outcomes probiotic therapy, improvements oxidative stress, anti-inflammatory effects, regulation neurotransmitters, restoration balance. aim this review to explore the potential probiotics management treatment investigating insights from recent animals. Lay abstract microbiota reservoir bacteria inhabiting our gastrointestinal tract. investigation into role disorder.

Language: Английский

---

Intestinal microbiota imbalance resulted by anti-Toxoplasma gondii immune responses aggravate gut and brain injury

Parasites & Vectors, Journal Year: 2024, Volume and Issue: 17(1)

Published: July 2, 2024

Abstract Background Toxoplasma gondii infection affects a significant portion of the global population, leading to severe toxoplasmosis and, in immunocompromised patients, even death. During T. infection, disruption gut microbiota further exacerbates damage intestinal and brain barriers. Therefore, identifying imbalanced probiotics during restoring their equilibrium can regulate balance metabolites, thereby alleviating tissue damage. Methods Vimentin gene knockout ( vim−/− ) mice were employed as an model evaluate influence host immune responses on infection. Behavioral experiments performed assess changes cognitive levels depressive tendencies between chronically infected wild-type (WT) mice. Fecal samples subjected 16S ribosomal RNA (rRNA) sequencing, serum metabolites analyzed identify potential for treatment Results Compared immunocompetent WT sv129 mice, exhibited lower neuronal apoptosis fewer neurobehavioral abnormalities chronic rRNA sequencing revealed decrease abundance probiotics, including several species Lactobacillus , Restoring this through administration murinus gasseri significantly suppressed burden intestine, liver, brain. Moreover, transplantation these two spp. improved barrier alleviated inflammation central nervous system. Metabolite detection studies that various -related indole-3-lactic acid (ILA) serum, decreased after We confirmed L. secreted much more ILA than . Notably, activate aromatic hydrocarbon receptor signaling pathway epithelial cells, promoting activation CD8 + T cells secretion interferon-gamma. Conclusion Our study against severely disrupted microbiota, resulting play crucial role regulation, metabolite is promising therapeutic compound efficient safe Graphical

Language: Английский

---

Neuroglial Dysregulation in Autism Spectrum Disorder: Pathogenetic Insights, Genetic Threads, and Therapeutic Horizons

Neuroglia, Journal Year: 2025, Volume and Issue: 6(1), P. 11 - 11

Published: March 1, 2025

Background/Objectives: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition marked by challenges in social communication, restricted interests, and repetitive behaviors. Recent studies highlight the crucial roles of neuroglial cells—astrocytes, microglia, oligodendrocytes—in synaptic function, neural connectivity, neuroinflammation. These findings offer fresh perspective on ASD pathophysiology. This review synthesizes current knowledge dysfunction ASD, emphasizing its role pathophysiological mechanisms, genetic influences, potential therapeutic strategies. Methods: We conducted comprehensive literature review, integrating insights from neuroscience, molecular biology, clinical studies. Special focus was given to glial-mediated neuroinflammatory plasticity regulation, impact mutations signaling homeostasis. Results: Neuroglial evident abnormal pruning impaired astrocytic glutamate defective oligodendrocyte-driven myelination, which collectively disrupt neuronal architecture. Emerging therapies targeting these pathways, including anti-inflammatory drugs, microglial modulators, cell-based approaches, show promise alleviating key symptoms. Additionally, advanced interventions such as gene editing glial progenitor therapy present opportunities correct underlying dysfunction. Conclusions: establishes framework for understanding contributions ASD. By diverse disciplines, it enhances our pathophysiology paves way novel strategies pathways.

Language: Английский

---

“The Effects of Oral Gestational Particulate Matter 10 Exposure: Insights into Neurodevelopmental Milestones, Inhibitory Control, Adult Sociability, and Object Recognition.”

NeuroToxicology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Air pollutants have been associated with various neurodevelopmental disorders, several studies specifically linking Particulate Matter (PM) exposure to attentional and social deficits. This link is even more pronounced when occurs during the prenatal period, as it can disrupt normal brain development. However, while deficits extensively studied adolescence, their impact on adult behaviors remains largely unexplored. To investigate these effects, pregnant Wistar rats were exposed throughout gestation (GD1-GD21) PM10 at a dosage of 200μg/Kg/day diluted in PBS that was freely drunk. After birth, pups evaluated developmental milestones such weight progression, ocular opening, muscular strength. In adulthood, inhibitory control assessed using Five Choice Serial Reaction Time Task (5-CSRTT), behavior Three-Chambered Crawley's Test (3-CT), object recognition Novelty Object Recognition test (NOR). The results indicated higher birth poorer performance neuromuscular tests. no significant differences observed (5-CSRTT) or (3-CT). Interestingly, prenatally rodents showed heightened novelty responses NOR test. conclusion, gestational related milestones, including While does not behavior, influences later life.

Language: Английский

---