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1.
Nutrients ; 14(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36364939

RESUMO

There is mounting evidence that the microbiota-gut-brain axis (MGBA) is critical in the pathogenesis and progression of Parkinson's disease (PD), suggesting that probiotic therapy restoring gut microecology may slow down disease progression. In this study, we examined the disease-alleviating effects of Bifidobacterium breve CCFM1067, orally administered for 5 weeks in a PD mouse model. Our study shows that supplementation with the probiotic B. breve CCFM1067 protected dopaminergic neurons and suppressed glial cell hyperactivation and neuroinflammation in PD mice. In addition, the antioxidant capacity of the central nervous system was enhanced and oxidative stress was alleviated. Moreover, B. breve CCFM1067 protected the blood-brain and intestinal barriers from damage in the MPTP-induced mouse model. The results of fecal microbiota analysis showed that B. breve CCFM1067 intervention could act on the MPTP-induced microecological imbalance in the intestinal microbiota, suppressing the number of pathogenic bacteria (Escherichia-Shigella) while increasing the number of beneficial bacteria (Bifidobacterium and Akkermansia) in PD mice. In addition, the increase in short chain fatty acids (acetic and butyric acids) may explain the anti-inflammatory action of B. breve CCFM1067 in the gut or brain of the MPTP-induced PD mouse model. In conclusion, we demonstrated that the probiotic B. breve CCFM1067, which can prevent or treat PD by modulating the gut-brain axis, can be utilized as a possible new oral supplement for PD therapy.


Assuntos
Bifidobacterium breve , Fármacos Neuroprotetores , Doença de Parkinson , Animais , Camundongos , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/etiologia , Doença de Parkinson/prevenção & controle , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/efeitos adversos , Bifidobacterium , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
2.
J Nutr Biochem ; 110: 109146, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36049672

RESUMO

Alternate-day fasting (ADF) regimen has been reported to alleviate obesity and insulin resistance. However, the effects of ADF on preventing diet-induced non-alcoholic fatty liver disease (NAFLD) and related cognitive deficits are still elusive. In the present study, a high-fat diet (HFD)-induced obese (DIO) C57BL/6 mouse model was established. Mice were treated with a 4-week long ADF regimen and/or switching the diet to a standard diet. ADF reduced lipid accumulation, activated AMPK/ULK1 signaling, and suppressed the phosphorylation of mTOR. Also, ADF inhibited lipid accumulation and inflammatory responses in the white adipose tissue and down-regulated expressions of PPAR-γ and cytokines. Moreover, ADF improved the working memory and synaptic structure in the DIO mice and upregulated PSD-95 and BDNF in the hippocampus. ADF reduced oxidative stress and microglial over-activation in the CNS. These results suggest that ADF attenuates NAFLD development in the liver of DIO mice, which is related to the mediating effects of ADF on autophagy and energy metabolism. ADF also enhanced cognitive function, which could be partly explained by the down-regulated peripheral inflammatory responses. This study indicates that ADF could be a promising intervention for alleviating NAFLD development and cognitive decline.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/metabolismo , Camundongos Obesos , Jejum , Memória de Curto Prazo , Camundongos Endogâmicos C57BL , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Obesidade/metabolismo , Lipídeos , Metabolismo dos Lipídeos
3.
Neurosci Biobehav Rev ; 135: 104556, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35122783

RESUMO

Alzheimer's disease (AD) is one of the fastest growing cognitive decline-related neurological diseases. To date, effective curative strategies have remained elusive. A growing body of evidence indicates that dietary patterns have significant effects on cognitive function and the risk of developing AD. Previous studies on the association between diet and AD risk have mainly focused on individual food components and specific nutrients, and the mechanisms responsible for the beneficial effects of dietary patterns on AD are not well understood. This article provides a comprehensive overview of the effects of dietary patterns, including the Mediterranean diet (MedDiet), dietary approaches to stop hypertension (DASH) diet, Mediterranean-DASH diet intervention for neurological delay (MIND), ketogenic diet, caloric restriction, intermittent fasting, methionine restriction, and low-protein and high-carbohydrate diet, on cognitive impairment and summarizes the underlying mechanisms by which dietary patterns attenuate cognitive impairment, especially highlighting the modulation of dietary patterns on cognitive impairment through gut microbiota. Furthermore, considering the variability in individual metabolic responses to dietary intake, we put forward a framework to develop personalized dietary patterns for people with cognitive disorders or AD based on individual gut microbiome compositions.


Assuntos
Doença de Alzheimer , Transtornos Cognitivos , Disfunção Cognitiva , Dieta Mediterrânea , Abordagens Dietéticas para Conter a Hipertensão , Doença de Alzheimer/psicologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/prevenção & controle , Humanos
4.
Food Funct ; 12(6): 2354-2377, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-33629669

RESUMO

Preliminary evidence shows the potential role of probiotics in ameliorating multiple sclerosis (MS); however, the effects of probiotics on MS remain unclear. Therefore, the aim of this study was to evaluate the efficacy of probiotics on multiple sclerosis by systematically reviewing the preclinical trials (animal trials) and performing meta-analysis of randomized controlled trials. PubMed, Web of Science, Cochrane central of randomized clinical trials, EMBASE, Clinical Trials, and a search engine Google Scholar were systematically searched and manually screened updated to November 2020, resulting in eligible 3 randomized controlled trials (RCTs) and 22 preclinical studies. Meta-analysis of RCTs enrolling 173 patients with MS receiving probiotics revealed significant beneficial effects of probiotic supplementation on mental health (expanded disability status scale scores: standardized mean difference [SMD] = -1.22; I2 = 92%; 95% CI, -2.40 to -0.03, P = 0.04; Beck depression inventory total scores: SMD = -1.58; I2 = 94%; 95% CI, -3.03 to -0.12; P = 0.03; general health questionnaire scores: SMD = -0.71; I2 = 0%; 95% CI, -1.02 to -0.40; P < 0.00001; depression anxiety and stress scale scores: SMD = -0.72; I2 = 0%; 95% CI, -1.12 to -0.33; P = 0.0003), with very low certainty of evidence. In addition, probiotic intake markedly improved insulin resistance and inflammatory and oxidative stress markers. Preclinical studies have shown that probiotic consumption reduces the incidence and severity of MS, delays MS progression (15 studies), and improves motor impairment (3 studies) with favorable alterations of immune and inflammatory markers (20 studies) and intestinal microbiome compositions (4 studies) in MS. These results indicated that probiotics may have beneficial effects on the prevention and treatment of multiple sclerosis.


Assuntos
Esclerose Múltipla/dietoterapia , Probióticos/uso terapêutico , Adulto , Animais , Feminino , Humanos , Inflamação , Masculino , Saúde Mental , Camundongos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Ratos , Adulto Jovem
5.
Biochim Biophys Acta Mol Basis Dis ; 1866(11): 165908, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32745530

RESUMO

Circadian misalignment induced by a high-fat diet (HFD) increases the risk of metabolic diseases. Methionine restriction (MR) is known to have the potential of alleviating obesity by improving insulin sensitivity. However, the role of the circadian clock in mediating the effects of MR on obesity-related metabolic disorders remains unclear. Ten-week-old male C57BL/6 J mice were fed with a low-fat diet (LFD) or a HFD for 4 wk., followed with a full diet (0.86% methionine, w/w) or a methionine-restricted diet (0.17% methionine, w/w) for 8 wk. Our results showed that MR attenuated insulin resistance triggered by HFD, especially at ZT12. Moreover, MR led to a time-specific enhancement of the expression of FGF21 and activated the AMPK/PGC-1α signaling. Notably, MR upregulated the cyclical levels of cholic acid (CA) and chenodeoxycholic acid (CDCA), and downregulated the cyclical level of deoxycholic acid (DCA) in the dark phase. MR restored the HFD-disrupted cyclical fluctuations of lipidolysis genes and BAs synthetic genes and improved the circulating lipid profile. Also, MR improved the expressions of clock-controlled genes (CCGs) in the liver and the brown adipose tissue throughout one day. In conclusion, MR exhibited the lipid-lowering effects on HFD-induced obesity and restored the diurnal metabolism of lipids and BAs, which could be partly explained by improving the expression of CCGs. These findings suggested that MR could be a potential nutritional intervention for attenuating obesity-induced metabolic misalignment.


Assuntos
Ácidos e Sais Biliares/metabolismo , Dieta Hiperlipídica/efeitos adversos , Metionina/deficiência , Obesidade/etiologia , Obesidade/metabolismo , Animais , Western Blotting , Ritmo Circadiano/fisiologia , Fatores de Crescimento de Fibroblastos/metabolismo , Imuno-Histoquímica , Metabolismo dos Lipídeos/fisiologia , Lipídeos , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Espectrometria de Massas em Tandem
6.
Mol Nutr Food Res ; 64(17): e2000190, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32729963

RESUMO

SCOPE: Methionine restriction (MR) is known to potently alleviate inflammation and improve gut microbiome in obese mice. The gut microbiome exhibits diurnal rhythmicity in composition and function, and this, in turn, drives oscillations in host metabolism. High-fat diet (HFD) strongly altered microbiome diurnal rhythmicity, however, the role of microbiome diurnal rhythmicity in mediating the improvement effects of MR on obesity-related metabolic disorders remains unclear. METHODS AND RESULTS: 10-week-old male C57BL/6J mice are fed a low-fat diet or HFD for 4 weeks, followed with a full diet (0.86% methionine, w/w) or a methionine-restricted diet (0.17% methionine, w/w) for 8 weeks. Analyzing microbiome diurnal rhythmicity at six time points, the results show that HFD disrupts the cyclical fluctuations of the gut microbiome in mice. MR partially restores these cyclical fluctuations, which lead to time-specifically enhance the abundance of short-chain fatty acids producing bacteria, increases the acetate and butyric, and dampens the oscillation of inflammation-related Desulfovibrionales and Staphylococcaceae over the course of 1 day. Notably, MR, which protects against systemic inflammation, influences brain function and synaptic plasticity. CONCLUSION: MR could serve as a potential nutritional intervention for attenuating obesity-induced cognitive impairments by balancing the circadian rhythm in microbiome-gut-brain homeostasis.


Assuntos
Ritmo Circadiano/fisiologia , Cognição/fisiologia , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/fisiologia , Metionina/farmacologia , Animais , Encéfalo/citologia , Encéfalo/metabolismo , Ritmo Circadiano/efeitos dos fármacos , Cognição/efeitos dos fármacos , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/microbiologia , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Aumento de Peso/efeitos dos fármacos
7.
Nat Commun ; 11(1): 855, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32071312

RESUMO

Cognitive decline is one of the complications of type 2 diabetes (T2D). Intermittent fasting (IF) is a promising dietary intervention for alleviating T2D symptoms, but its protective effect on diabetes-driven cognitive dysfunction remains elusive. Here, we find that a 28-day IF regimen for diabetic mice improves behavioral impairment via a microbiota-metabolites-brain axis: IF enhances mitochondrial biogenesis and energy metabolism gene expression in hippocampus, re-structures the gut microbiota, and improves microbial metabolites that are related to cognitive function. Moreover, strong connections are observed between IF affected genes, microbiota and metabolites, as assessed by integrative modelling. Removing gut microbiota with antibiotics partly abolishes the neuroprotective effects of IF. Administration of 3-indolepropionic acid, serotonin, short chain fatty acids or tauroursodeoxycholic acid shows a similar effect to IF in terms of improving cognitive function. Together, our study purports the microbiota-metabolites-brain axis as a mechanism that can enable therapeutic strategies against metabolism-implicated cognitive pathophysiologies.


Assuntos
Disfunção Cognitiva/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Jejum , Microbioma Gastrointestinal/fisiologia , Animais , Encéfalo/metabolismo , Cognição , Biologia Computacional , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2/complicações , Metabolismo Energético/genética , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/genética , Regulação da Expressão Gênica , Hipocampo/metabolismo , Indóis/metabolismo , Resistência à Insulina , Masculino , Metaboloma , Camundongos , Propionatos/metabolismo , RNA Ribossômico 16S , Serotonina/metabolismo , Sinapses/ultraestrutura , Ácido Tauroquenodesoxicólico/metabolismo
8.
J Agric Food Chem ; 67(22): 6190-6201, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31117496

RESUMO

Sesamol, an antioxidant lignan from sesame oil, possesses neuroprotective bioactivities. The present work was aimed to elucidate the systemic protective effects of sesamol on cognitive deficits and to determine the possible link between gut and brain. Wildtype and ApoE-/- mice were treated with a high-fat diet and sesamol (0.05%, w/v, in drinking water) for 10 weeks. Behavioral tests including Morris-water maze, Y-maze, and elevated plus maze tests indicated that sesamol could only improve cognitive deficits and anxiety behaviors in wildtype. Consistently, sesamol improved synapse ultrastructure and inhibited Aß accumulation in an ApoE-dependent manner. Moreover, sesamol prevented dietary-induced gut barrier damages and systemic inflammation. Sesamol also reshaped gut microbiome and improved the generation of microbial metabolites short-chain fatty acids. To summarize, this study revealed that the possible mechanism of neuroprotective effects of sesamol might be ApoE-dependent, and its beneficial effects on gut microbiota/metabolites could be translated into neurodegenerative diseases treatment.


Assuntos
Apolipoproteínas E/metabolismo , Benzodioxóis/administração & dosagem , Encéfalo/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Fenóis/administração & dosagem , Óleo de Gergelim/química , Animais , Apolipoproteínas E/genética , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/isolamento & purificação , Bactérias/metabolismo , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/microbiologia , Ácidos Graxos Voláteis/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
9.
J Nutr Biochem ; 64: 61-71, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30445417

RESUMO

Depression is a mood disorder that is related to neuroinflammation and cognition loss. This study is aimed to determine the potential antidepressant effects of (+)-sesamin, a lignan component of sesame, in a mild stress-induced depression mouse model. CD-1 mice were treated with chronic unpredictable mild stress (CUMS) process and orally administrated with sesamin (50 mg/kg/d) for 6 weeks. Behavioral tests including forced swimming test, tail suspension test, open field test, and elevated plus maze test demonstrated that sesamin treatment inhibited CUMS-induced mice depressant-like behaviors and anxiety, without changing immobility. It was found that sesamin prevented stress-induced decease levels of 5-HT and NE in striatum and serum. Cognitive deficits were assessed using Y-maze and Morris water maze test. Sesamin treatment also prevented stressed-induced memory impairments and neuronal damages. Consistently, sesamin also enhanced synapse ultrastructure and improved expressions of PSD-95 in stressed mice hippocampus with improving neurotrophic factors expression including BDNF and NT3. Moreover, sesamin treatment significantly prevented CUMS-induced neuroinflammation by inhibiting over-activation of microglia and expressions of inflammatory mediators including iNOS, COX-2, TNF-α and IL-1ß in stressed mice hippocampus and cortex. These results illustrated that sesamin markedly improved CUMS-induced depression and memory loss via inhibiting neuroinflammation, which indicate that as food component, sesamin might be also a novel potential therapeutic for depression.


Assuntos
Antidepressivos/farmacologia , Encéfalo/efeitos dos fármacos , Depressão/dietoterapia , Dioxóis/farmacologia , Inflamação/dietoterapia , Lignanas/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Citocinas/genética , Citocinas/metabolismo , Depressão/etiologia , Suplementos Nutricionais , Modelos Animais de Doenças , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/dietoterapia , Camundongos Endogâmicos , Proteínas do Tecido Nervoso/metabolismo , Norepinefrina/sangue , Norepinefrina/metabolismo , Serotonina/sangue , Serotonina/metabolismo
10.
Food Funct ; 8(12): 4657-4667, 2017 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-29159335

RESUMO

Acrylamide (ACR) is a chronic neurotoxin that is generated in high-starch foods during heat processing. Alpha-lipoic acid (LA) is an antioxidant that occurs in most plants and animals. The objective of this study was to reveal the mechanism of ACR-triggered neurotoxicity and identify the protective role of LA in SH-SY5Y cells. In this study, LA restored ACR-stimulated depletion of glutathione content and mitochondrial membrane potential, moderated the activation of inflammatory pathways, and recovered the Keap1/Nrf2 pathway. Moreover, LA upregulated the activities of oxidative phosphorylation complexes and diminished ACR-induced variation in AMPK/GSK3ß, Ca2+ disturbance, and ATP depletion. The Sirt1/PGC-1α pathway was inhibited by ACR. Notably, autophagy was activated in the mitochondria-mediated apoptosis induced by ACR, which was also blocked by LA. Overall, our study demonstrated the pivotal roles of the mitochondrial energy metabolism and autophagy in the protective effects of LA and cytotoxicity of ACR in SH-SY5Y cells.


Assuntos
Acrilamida/toxicidade , Autofagia/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ácido Tióctico/farmacologia , Apoptose/efeitos dos fármacos , Glutationa/metabolismo , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Estresse Oxidativo/efeitos dos fármacos
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