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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Childhood maltreatment influences adult brain structure through its effects on immune, metabolic, and psychosocial factors

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(16)

Published: April 9, 2024

Childhood maltreatment (CM) leads to a lifelong susceptibility mental ill-health which might be reflected by its effects on adult brain structure, perhaps indirectly mediated metabolic, immune, and psychosocial systems. Indexing these systemic factors via body mass index (BMI), C-reactive protein (CRP), rates of trauma (AT), respectively, we tested three hypotheses: (H1) CM has direct or indirect trauma, BMI, CRP; (H2) CRP are all independently related structure; (H3) childhood structure in parallel CRP, AT. Using path analysis data from

Language: Английский

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A narrative review about cognitive impairment in Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD): Another matter to face through a holistic approach

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: 68, P. 231 - 240

Published: Feb. 17, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic hepatic disorder worldwide in both adults and children. It well established that MASLD represents manifestation of metabolic syndrome whose definition includes presence obesity, type 2 diabetes (T2D), dyslipidemia, hypertension hypercoagulability. All these conditions contribute to a inflammatory status which may impact on blood brain barrier (BBB) integrity leading an impaired function central nervous system (CNS). Since mechanisms underlying brain-liver-gut axis derangement are still inconclusive, present narrative review aims make roundup recent studies regarding cognitive decline also highlighting possible therapeutic strategies reach holistic advantage for patients. Due its ever-growing prevalence, MASLD-related mental dysfunction enormous socio-economic burden since it largely impacts quality life patients as their working productivity. Indeed, translates low concentration processing speed, reduced memory, sleepiness but anxiety depression. Chronic systemic inflammation, hyperammonemia, genetic background intestinal dysbiosis possibly However, diagnosis underestimated multi-faceted unexplained do not exist standardized diagnostic tools or test strategies. In this scenario, nutritional lifestyle interventions microbiota manipulation (probiotics, fecal transplantation) represent new approaches counteract impairment subjects. sum, face "mental aspect" multifactorial almost unexplored, should be introduced management

Language: Английский

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Obesity-induced chronic low-grade inflammation in adipose tissue: A pathway to Alzheimer’s disease

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 99, P. 102402 - 102402

Published: July 6, 2024

Alzheimer's disease (AD) is a leading cause of cognitive impairment worldwide. Overweight and obesity are strongly associated with comorbidities, such as hypertension, diabetes, insulin resistance (IR), which contribute substantially to the development AD subsequent morbidity mortality. Adipose tissue (AT) highly dynamic organ composed diverse array cell types, can be classified based on their anatomic localization or cellular composition. The expansion remodeling AT in context involves immunometabolic functional shifts steered by intertwined actions multiple immune cells cytokine signaling within AT, metabolic disorders, IR, systemic markers chronic low-grade inflammation. Chronic inflammation, prolonged, low-dose stimulation specific immunogens that progress from localized sites affect organs throughout body, leads neurodystrophy, increased apoptosis, disruption homeostasis, manifesting brain atrophy AD-related pathology. In this review, we sought elucidate mechanisms contributes onset progression through mediation particularly focusing roles adipokines AT-resident cells.

Language: Английский

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Intermittent fasting alleviates postoperative cognitive dysfunction by reducing neuroinflammation in aged mice

Brain Research Bulletin, Journal Year: 2024, Volume and Issue: 216, P. 111034 - 111034

Published: July 23, 2024

Elderly individuals undergoing surgical procedures are often confronted with the peril of experiencing postoperative cognitive dysfunction (POCD). Prior research has demonstrated exacerbating effect sevoflurane anesthesia on neuroinflammation, which can further deteriorate condition POCD in elderly patients. Intermittent fasting (IF) restricts food consumption to a specific time window and been ameliorate induced by neuropathic inflammation. We subjected 18-month-old male mice 16 hours 8 unrestricted eating over 24-hour period for 0, 1, 2, 4 weeks, followed abdominal exploration under anesthesia. In this study, we aim explore potential impact IF function aged surgery through preoperative implementation measures. The findings indicate two weeks leads significant enhancement learning memory capabilities following surgery. performance, as determined novel object recognition Morris water maze tests, well synaptic plasticity, measured vivo electrophysiological recordings, marked improvements. Furthermore, administration markedly enhances expression synaptic-associated proteins hippocampal neurons, concomitant decreasing pro-inflammatory factors reduced density microglial cells within brain region. To summarize, results study that may mitigate inflammation area brain. appears provide safeguard against impairment plasticity brought

Language: Английский

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Neuro-Adipokine Crosstalk in Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 5932 - 5932

Published: May 29, 2024

The connection between body weight alterations and Alzheimer’s disease highlights the intricate relationship brain adipose tissue in context of neurological disorders. During midlife, gain increases risk cognitive decline dementia, whereas late life, becomes a protective factor. Despite their substantial impact on metabolism, role adipokines transition from healthy aging to disorders remains largely unexplored. We aim investigate how milieu secreted are involved biological pathological aging, highlighting bidirectional systemic metabolism. Understanding function these will allow us identify biomarkers for early detection uncover novel therapeutic options.

Language: Английский

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Development and validation of Galectin-3 and CVAI-based model for predicting cognitive impairment in type 2 diabetes

Journal of Endocrinological Investigation, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 20, 2024

Language: Английский

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Cognitive Impairment in MASLD is associated with Amygdala-Related Connectivity Dysfunction in the Prefrontal and Sensory Cortex

Journal of Integrative Neuroscience, Journal Year: 2024, Volume and Issue: 23(12)

Published: Dec. 11, 2024

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common metabolism-related multisystem clinical disorder, often accompanied by high comorbidity of mild cognitive impairment (MCI). Increasing evidence suggests that the amygdala crucial in processing during metabolic dysfunction. Nevertheless, role neural mechanisms MASLD with MCI (MCI_MASLD) remains unclear. Methods: A total 74 patients (43 MCI_MASLD and 31 without [nonMCI_MASLD]) 62 demographic-matched healthy controls (HC) were enrolled. All participants underwent resting-state functional magnetic resonance imaging scans psychological scale assessments. Liver fat content blood index measurements performed on patients. Using bilateral as seeds, seed-based connectivity (FC) maps calculated one-way analysis covariance post hoc tests was to investigate difference among three groups. Results: Compared nonMCI_MASLD patients, demonstrated enhanced FC between right medial prefrontal cortex (mPFC), while reduced left supplementary motor area (SMA). Interestingly, values mPFC correlated Montreal Cognitive Assessment Scale (MoCA) scores controlled attenuation parameters, SMA also MoCA scores. Furthermore, regions within frontal-limbic-mesencephalic circuits higher when compared HC. Conclusions: Aberrant can provide potential neuroimaging markers for MASLD, which associated amygdala-related disturbances areas related cognition sensory processing. Moreover, visceral accumulation may exacerbate brain

Language: Английский

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