Circulatory dietary and gut-derived metabolites predict preclinical Alzheimer's disease. DOI Creative Commons
Emily Connell, Saber Sami, Mizanur Khondoker

et al.

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

Published: May 10, 2024

Abstract A key component of disease prevention is the identification at-risk individuals. Microbial dysbiosis and microbe-derived metabolites (MDM) can influence central nervous system, but their role in progression as prognostic indicators unknown. To identify preclinical factors associated with Alzheimer’s (AD), we compared gut microbiome metabolome profiles cognitively healthy subjects, subjective cognitive impairment (SCI) participants mild (MCI) (n=50 per group, matched for age, BMI sex), targeting previously health (TMAO, bile acids, tryptophan, p -cresol derivatives). 16S rRNA bacterial sequencing targeted LC-MS/MS were employed faecal speciation serum MDM quantification. Microbiome beta diversity differed between controls SCI participants. Multiple linear regression modelling highlighted five (indoxyl sulfate, choline, 5-hydroxyindole acetic acid, indole-3-propionic acid (IPA) kynurenic acid) significantly altered AD. Neuroprotective metabolites, including IPA, exhibited lower concentrations MCI comparison to controls, while cytotoxic metabolite indoxyl sulfate had higher levels. Random Forest algorithm multiclass classification confirmed extended our results, identifying six kynurenine) predictors early decline, an area under curve 0.74. In summary, a combined statistical machine learning approach identified novel composite risk factor future dementia risk.

Language: Английский

Pasteurized Akkermansia muciniphila improves irritable bowel syndrome-like symptoms and related behavioral disorders in mice DOI Creative Commons
Maëva Meynier,

Valentine Daugey,

Geoffroy Mallaret

et al.

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

Published: Jan. 3, 2024

Gut – brain communications disorders in irritable bowel syndrome (IBS) are associated with intestinal microbiota composition, increased gut permeability, and psychosocial disturbances. Symptoms of IBS difficult to medicate, hence much research is being made into alternative approaches. This study assesses the potential a treatment pasteurized Akkermansia muciniphila for alleviating IBS-like symptoms two mouse models different etiologies. Two clinically relevant animal were used mimic C57BL6/J mice: neonatal maternal separation (NMS) paradigm Citrobacter rodentium infection model. In both models, colonic sensitivity, fecal composition IL-22 expression evaluated. The cognitive performance emotional state animals also assessed by several tests C. neuromodulation ability A. was on primary neuronal cells from mice dorsal root ganglia using ratiometric calcium imaging approach. administration significantly reduced hypersensitivity accompanied reinforcement barrier function. Beneficial effects have been observed anxiety-like behavior memory defects Finally, neuroinhibitory effect exerted stimulated algogenic substances such as capsaicin inflammatory soup. Our findings demonstrate novel anti-hyperalgesic properties muciniphila, which therefore may beneficial relieving pain anxiety subjects IBS.

Language: Английский

Citations

32
A Proteomic Approach Identified TFEB as a Key Player in the Protective Action of Novel CB2R Bitopic Ligand FD22a against the Deleterious Effects Induced by β-Amyloid in Glial Cells DOI Creative Commons
Beatrice Polini, Lorenzo Zallocco, Francesca Gado

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(10), P. 875 - 875

Published: May 19, 2024

Neurodegenerative diseases (NDDs) are progressive multifactorial disorders of the nervous system sharing common pathogenic features, including intracellular misfolded protein aggregation, mitochondrial deficit, and inflammation. Taking into consideration multifaceted nature NDDs, development multitarget-directed ligands (MTDLs) has evolved as an attractive therapeutic strategy. Compounds that target cannabinoid receptor type II (CB2R) rapidly emerging novel effective MTDLs against such Alzheimer's disease (AD). We recently developed first CB2R bitopic/dualsteric ligand, namely FD22a, which revealed ability to induce neuroprotection with fewer side effects. To explore potential FD22a a multitarget drug for treatment we investigated here its prevent toxic effect β-amyloid (Aβ

Language: Английский

Citations

5
Raspberry Ketone Prevents LPS‐Induced Depression‐Like Behaviors in Mice by Inhibiting TLR‐4/NF‐κB Signaling Pathway via the Gut‐Brain Axis DOI
Yike Liu,

Chenlin Dai,

Chendi Wang

et al.

Molecular Nutrition & Food Research, Journal Year: 2024, Volume and Issue: 68(11)

Published: May 17, 2024

Scope Depression, a prevalent mental disorder, has significantly impacted the lives of 350 million people, yet it holds promise for amelioration through food‐derived phenolics. Raspberries, renowned globally their delectable flavor, harbor phenolic compound known as raspberry ketone (RK). However, impact RK on depressive symptoms remains ambiguous. This study aims to investigate lipopolysaccharide (LPS)‐induced depressed mice and elucidates its potential mechanisms, focusing gut‐brain axis. Methods results Through behavioral tests, exerts notable preventive effect LPS‐induced depression‐like behaviors in mice. proves capable attenuating gut inflammation, repairing barrier impairment, modulating composition microbiome ( Muribaculaceae , Streptococcus Lachnospiraceae Akkermansia ), promoting production short‐chain fatty acids. Furthermore, alleviates neuroinflammation by suppressing TLR‐4/NF‐κB pathway bolsters synaptic function elevating levels neurotrophic factors synapse‐associated proteins. Conclusion The current provides compelling evidence that effectively inhibits via axis, leading improvement addresses research gap understanding antidepressant effects illuminates utilizing functional food preventing depression.

Language: Английский

Citations

4
Health benefits of medicinal plant natural products via microbiota-mediated different gut axes DOI Creative Commons
Xiang Li, Yufan Liu, Ning Liu

et al.

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107730 - 107730

Published: April 1, 2025

This review examines the multifaceted roles of medicinal plant natural products in influencing gut microbiota and their subsequent impact on various organ systems through established axes, including gut-brain, gut-liver, gut-heart, gut-lung, gut-kidney axes. Medicinal have exhibited diverse pharmacological activities, modulation composition, enhancement metabolic processes, alleviation inflammation oxidative stress. Evidence suggests that these components can ameliorate conditions such as neurological disorders, syndrome, chronic kidney disease by restoring microbial balance improving barrier integrity. Furthermore, highlights potential to foster beneficial communities improve health, which may lead reduced severity inflammation. By comprehensively analyzing current literature, this provides a foundation for future research aim at exploring therapeutic applications prevention treatment. The findings underscore need further studies elucidate underlying mechanisms action validate clinical efficacy managing modulation.

Language: Английский

Citations

0
The antidepressant potential of saffron (Crocus sativus L.): molecular mechanisms, neurotransmitter modulation, gut-brain axis interactions, and clinical efficacy in major depressive disorder DOI

Zhen‐Zhen Lai,

Yingying Cao, Liang Yu

et al.

Phytochemistry Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: May 8, 2025

Language: Английский

Citations

0
Saffron, a Potential Bridge between Nutrition and Disease Therapeutics: Global Health Challenges and Therapeutic Opportunities DOI Creative Commons
Rakeeb Ahmad Mir, Anshika Tyagi,

Sofi Javed Hussain

et al.

Plants, Journal Year: 2024, Volume and Issue: 13(11), P. 1467 - 1467

Published: May 25, 2024

Plants are an important source of essential bioactive compounds that not only have a beneficial role in human health and nutrition but also act as drivers for shaping gut microbiome. However, the mechanism their functional attributes is fully understood despite significance. One such plant

Language: Английский

Citations

3
A novel Mediterranean diet-inspired supplement ameliorates cognitive, microbial, and metabolic deficits in a mouse model of low-grade inflammation DOI Creative Commons
Matthew G. Pontifex, Emily Connell, Gwénaëlle Le Gall

et al.

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

Published: June 4, 2024

The Mediterranean diet (MD) and its bioactive constituents have been advocated for their neuroprotective properties along with capacity to affect gut microbiota speciation metabolism. Mediated through the brain axis, this modulation of may partly contribute MD. To explore potential interaction, we evaluated a novel blend (Neurosyn240) resembling in rodent model chronic low-grade inflammation. Behavioral tests cognition, proteomic analysis, 16S rRNA sequencing, 1H NMR metabolomic analyses were employed develop an understanding gut-brain axis interactions involved. Recognition memory, as assessed by object recognition task (NOR), decreased response LPS insult was restored Neurosyn240 supplementation. Although open field performance did not reach significance, it correlated NOR indicating element anxiety related cognitive change. changes associated accompanied shift composition which included restoration Firmicutes: Bacteroidota ratio increase Muribaculum, Rikenellaceae Alloprevotella, most notably Akkermansia significantly performance. also metabolites 5-aminovalerate, threonine, valine, uridine monophosphate, adenosine turn profile within dramatically influenced both interventions, KEGG analysis highlighting oxidative phosphorylation neurodegenerative disease-related pathways be modulated. Intriguingly, subset these simultaneously abundance predominantly phosphorylation, perhaps alluding protective interaction. Collectively, our results suggest that conferred resilience deleterious effects

Language: Английский

Citations

3
Integration of 16 S rRNA gene sequencing, metabonomics and metagenome analysis to investigate the mechanism of Sparganium stoloniferum-Curcuma phaeocaulis in treating of endometriosis in rats DOI
Weilin Zheng, Hong Zhou,

Zhiyi Fu

et al.

Journal of Pharmaceutical and Biomedical Analysis, Journal Year: 2024, Volume and Issue: 241, P. 115970 - 115970

Published: Jan. 21, 2024

Language: Английский

Citations

2
Microbiota–gut–brain axis: Natural antidepressants molecular mechanism DOI

Yitong Lu,

Xiaowen Yu, Zhongling Wang

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 134, P. 156012 - 156012

Published: Aug. 31, 2024

Language: Английский

Citations

2
(Poly)phenol-rich grape and blueberry extract prevents LPS-induced disruption of the blood-brain barrier through the modulation of the gut microbiota-derived uremic toxins DOI Creative Commons
Emily Connell, Gwénaëlle Le Gall, Simon McArthur

et al.

Neurochemistry International, Journal Year: 2024, Volume and Issue: 180, P. 105878 - 105878

Published: Oct. 9, 2024

The dynamic protective capacity of (poly)phenols, attributed to their potent antioxidant and anti-inflammatory properties, has been consistently reported. Due alter gut microbiome composition, further actions (poly)phenols may be exerted through the modulation microbiota-gut-brain axis. However, underlying mechanisms remain poorly defined. Here, we investigated effect a (poly)phenol-rich grape blueberry extract (Memophenol™), on axis in model chronic low-grade inflammation (0.5 mg/kg/wk lipopolysaccharide (LPS) for 8 weeks). Dietary supplementation male C57BL/6 J mice with Memophenol™ prevented LPS-induced increases microbe-derived uremia-associated molecules, indoxyl sulfate (IS) trimethylamine N-oxide (TMAO). These changes coincided shifts notably Romboutsia Desulfovibrio abundance, respectively. In brain, LPS exposure disrupted marginal localisation endothelial tight junction ZO-1 downregulated mRNA expression an extent closely correlated TMAO IS levels; process by intake. Hippocampal sequencing analysis revealed significant downregulation regulatory pathways neurodegeneration findings indicate novel role component ZO-1, acting microbial metabolism.

Language: Английский

Citations

2