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

---

The Potential Role of Gut Microbiota in Alzheimer’s Disease: From Diagnosis to Treatment

Nutrients, Journal Year: 2022, Volume and Issue: 14(3), P. 668 - 668

Published: Feb. 5, 2022

Gut microbiota is emerging as a key regulator of many disease conditions and its dysregulation implicated in the pathogenesis several gastrointestinal extraintestinal disorders. More recently, gut microbiome alterations have been linked to neurodegeneration through increasingly defined brain axis, opening possibility for new microbiota-based therapeutic options. Although studies conducted unravel possible relationship between Alzheimer’s Disease (AD) progression, diagnostic potential approaches aiming at restoring eubiosis remain be fully addressed. In this narrative review, we briefly summarize role homeostasis health disease, present evidence AD patients. Based on these observations, then discuss how dysbiosis might exploited tool early advanced stages, examine prebiotics, probiotics, fecal transplantation, diets complementary interventions thus offering insights into diagnosis treatment devastating progressive disease.

Language: Английский

---

Gut microbiome composition may be an indicator of preclinical Alzheimer’s disease

Science Translational Medicine, Journal Year: 2023, Volume and Issue: 15(700)

Published: June 14, 2023

Alzheimer’s disease (AD) pathology is thought to progress from normal cognition through preclinical and ultimately symptomatic AD with cognitive impairment. Recent work suggests that the gut microbiome of patients has an altered taxonomic composition compared healthy, cognitively control individuals. However, knowledge about changes in before onset limited. In this cross-sectional study accounted for clinical covariates dietary intake, we microbial function a cohort 164 individuals, 49 whom showed biomarker evidence early AD. Gut profiles individuals were distinct those without The change correlated β-amyloid (Aβ) tau pathological biomarkers but not neurodegeneration, suggesting may process. We identified specific bacterial taxa associated Inclusion these features improved accuracy, sensitivity, specificity machine learning classifiers predicting status when tested on subset (65 participants). correlates neuropathology improve our understanding etiology help identify gut-derived markers risk.

Language: Английский

---

The gut microbiome in Alzheimer’s disease: what we know and what remains to be explored

Molecular Neurodegeneration, Journal Year: 2023, Volume and Issue: 18(1)

Published: Feb. 1, 2023

Alzheimer's disease (AD), the most common cause of dementia, results in a sustained decline cognition. There are currently few effective modifying therapies for AD, but insights into mechanisms that mediate onset and progression may lead to new, therapeutic strategies. Amyloid beta oligomers plaques, tau aggregates, neuroinflammation play critical role neurodegeneration impact clinical AD progression. The upstream modulators these pathological features have not been fully clarified, recent evidence indicates gut microbiome (GMB) an influence on therefore human patients. In this review, we summarize studies identified alterations GMB correlate with pathophysiology patients mouse models. Additionally, discuss findings manipulations models potential GMB-targeted therapeutics AD. Lastly, diet, sleep, exercise as modifiers relationship between conclude future directions recommendations further topic.

Language: Английский

---

Microbiota-derived metabolite Indoles induced aryl hydrocarbon receptor activation and inhibited neuroinflammation in APP/PS1 mice

Brain Behavior and Immunity, Journal Year: 2022, Volume and Issue: 106, P. 76 - 88

Published: Aug. 10, 2022

Gut microbiota alterations might affect the development of Alzheimer's disease (AD) through microbiota-derived metabolites. For example, Indoles via tryptophan metabolism prevented Aβ accumulation and Tau hyperphosphorylation, restored synaptic plasticity, then promoted cognitive behavioral ability APP/PS1 mice. The imbalanced compositions Indoles-producing bacteria with deficiency were found in male mice, but molecular mechanisms remained unclear. Our current study revealed that (including indole, indole-3-acetic acid indole-3-propionic acid) upregulated production aryl hydrocarbon receptor (AhR), inhibited activation NF-κB signal pathway as well formation NLRP3 inflammasome, reduced release inflammatory cytokines, including TNF-α, IL-6, IL-1β IL-18, alleviating response These findings demonstrated roles activating AhR to regulate neuroinflammation AD gut Indoles, which implied a novel way for treatment.

Language: Английский

---

Cognitive enhancement and neuroprotective effects of OABL, a sesquiterpene lactone in 5xFAD Alzheimer's disease mice model

Redox Biology, Journal Year: 2022, Volume and Issue: 50, P. 102229 - 102229

Published: Jan. 8, 2022

Alzheimer's disease (AD) is a neurodegenerative in which oxidative stress and neuroinflammation were demonstrated to be associated with neuronal loss cognitive deficits. However, there are still no specific treatments that can prevent the progression of AD. In this study, screening anti-inflammatory hits from 4207 natural compounds two different molecular libraries indicated 1,6-O,O-diacetylbritannilactone (OABL), 1,10-seco-eudesmane sesquiterpene lactone isolated herb Inula britannica L., exhibited strong activity vitro as well favorable BBB penetration property. OABL reduced LPS-induced BV-2 microglial cells assessed by effects on levels inflammatory mediators including NO, PGE2, TNF-α, iNOS, COX-2, translocation NF-κB. Besides, also pronounced neuroprotective against oxytosis ferroptosis rat pheochromocytoma PC12 cell line. For vivo research, (20 mg/kg B.W., i.p.) for 21 d attenuated impairments function observed 6-month-old 5xFAD mice, Morris water maze test. restored damage postsynaptic density protein 95 (PSD95) expression hippocampus. significantly accumulation amyloid plaques, Aβ expression, phosphorylation Tau protein, BACE1 AD mice brain. addition, overactivation microglia astrocytes suppressing expressions cytokines, increased glutathione (GSH) malondialdehyde (MDA) super oxide dismutase (SOD) conclusion, these results highlight beneficial product novel treatment potential application drug discovery due its pharmacological profile.

Language: Английский

---

Association of Dietary Live Microbes and Nondietary Prebiotic/Probiotic Intake With Cognitive Function in Older Adults: Evidence From NHANES

The Journals of Gerontology Series A, Journal Year: 2023, Volume and Issue: 79(2)

Published: July 22, 2023

Abstract Background The current study aims to examine association of dietary live microbes and nondietary prebiotic/probiotic intake with cognitive function among older U.S. adults, examining heterogeneity across demographic characteristics diseases. Methods Participants from the National Health Nutrition Examination Survey 2011–2014 cycles were selected administered 3 tests: Consortium Establish a Registry for Alzheimer’s Disease Word Learning subtest (CERAD W-L, including immediate [CERAD-IRT] delayed [CERAD-DRT] memory), Animal Fluency Test (AFT), Digit Symbol Substitution (DSST). Test-specific global cognition z-score was created. Based on their estimated intake, participants categorized into three groups: low, medium, high. Text mining employed identify usage by names ingredients supplements or drugs. Results in medium (including AFT) high cognition, AFT, DSST, CERAD-IRT) group had significantly higher compared those low group. Among cardiovascular disease history, prebiotic associated CERAD-DRT who did not consume prebiotic. Additionally, probiotic linked particularly diabetes mellitus hypertension. Conclusions Our suggests that probiotic/prebiotic better specific states.

Language: Английский

---

Short-Chain Fatty Acids and Human Health: From Metabolic Pathways to Current Therapeutic Implications

Life, Journal Year: 2024, Volume and Issue: 14(5), P. 559 - 559

Published: April 26, 2024

The gastrointestinal tract is home to trillions of diverse microorganisms collectively known as the gut microbiota, which play a pivotal role in breaking down undigested foods, such dietary fibers. Through fermentation these food components, short-chain fatty acids (SCFAs) acetate, propionate, and butyrate are produced, offering numerous health benefits host. production absorption SCFAs occur through various mechanisms within human intestine, contingent upon types fibers reaching specific engaged fermentation. Medical literature extensively documents supplementation SCFAs, particularly butyrate, treatment gastrointestinal, metabolic, cardiovascular, gut-brain-related disorders. This review seeks provide an overview dynamics involved gut. Additionally, it will focus on roles promoting metabolic health, well their current therapeutic implications.

Language: Английский

---

Gut microbiome-targeted therapies for Alzheimer’s disease

Gut Microbes, Journal Year: 2023, Volume and Issue: 15(2)

Published: Nov. 7, 2023

The advent of high­throughput ‘omics’ technologies has improved our knowledge gut microbiome in human health and disease, including Alzheimer’s disease (AD), a neurodegenerative disorder. Frequent bidirectional communications mutual regulation exist between the gastrointestinal tract central nervous system through gut-brain axis. A large body research reported close association microbiota AD development, restoring healthy may curb or even improve symptoms progression. Thus, modulation become novel paradigm for clinical management AD, emerging effort focused on developing potential strategies preventing and/or treating disease. In this review, we provide an overview connection causal relationship dysbiosis mechanisms driving progression, successes challenges implementing available microbiome-targeted therapies (including probiotics, prebiotics, synbiotics, postbiotics, fecal transplantation) preventive therapeutic preclinical intervention studies AD. Finally, discuss future directions field.

Language: Английский

---

The Role of Diet and Gut Microbiota in Alzheimer’s Disease

Nutrients, Journal Year: 2024, Volume and Issue: 16(3), P. 412 - 412

Published: Jan. 31, 2024

Alzheimer’s disease (AD), the most prevalent form of dementia, is characterized by accumulation amyloid-beta (Aβ) plaques and hyperphosphorylated tau tangles. Currently, (AD) impacts 50 million individuals, with projections anticipating an increase to 152 year 2050. Despite increasing global prevalence AD, its underlying pathology remains poorly understood, posing challenges for early diagnosis treatment. Recent research suggests a link between gut dysbiosis aggregation Aβ, development proteins, occurrence neuroinflammation oxidative stress are associated AD. However, investigations into gut–brain axis (GBA) in context AD progression have yielded inconsistent findings. This review aims enhance our understanding microbial diversity at species level role these pathology. Additionally, this addresses influence confounding elements, including diet, probiotics, prebiotics, on throughout different stages (preclinical, mild cognitive impairment (MCI), AD) progression.

Language: Английский

---