scholarly journals Association of Gut Microbiome Dysbiosis with Neurodegeneration: Can Gut Microbe-Modifying Diet Prevent or Alleviate the Symptoms of Neurodegenerative Diseases?

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 698
Author(s):  
Li Yang Tan ◽  
Xin Yi Yeo ◽  
Han-Gyu Bae ◽  
Delia Pei Shan Lee ◽  
Roger C. Ho ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Gut Microbiome ◽  
Disease Onset ◽  
Gastrointestinal Symptoms ◽  
Dietary Interventions ◽  
Gut Dysbiosis ◽  
Dietary Choices ◽  
Gut Microbe ◽  
The Central Nervous System ◽  
The Impact

The central nervous system was classically perceived as anatomically and functionally independent from the other visceral organs. But in recent decades, compelling evidence has led the scientific community to place a greater emphasis on the role of gut microbes on the brain. Pathological observations and early gastrointestinal symptoms highlighted that gut dysbiosis likely precedes the onset of cognitive deficits in Alzheimer’s disease (AD) and Parkinson’s disease (PD) patients. The delicate balance in the number and functions of pathogenic microbes and alternative probiotic populations is critical in the modulation of systemic inflammation and neuronal health. However, there is limited success in restoring healthy microbial biodiversity in AD and PD patients with general probiotics interventions and fecal microbial therapies. Fortunately, the gut microflora is susceptible to long-term extrinsic influences such as lifestyle and dietary choices, providing opportunities for treatment through comparatively individual-specific control of human behavior. In this review, we examine the impact of restrictive diets on the gut microbiome populations associated with AD and PD. The overall evidence presented supports that gut dysbiosis is a plausible prelude to disease onset, and early dietary interventions are likely beneficial for the prevention and treatment of progressive neurodegenerative diseases.

scholarly journals Implications of Diet and The Gut Microbiome in Neuroinflammatory and Neurodegenerative Diseases

2019 ◽  
Vol 20 (12) ◽  
pp. 3109 ◽  
Author(s):  
Sarah Hirschberg ◽  
Barbara Gisevius ◽  
Alexander Duscha ◽  
Aiden Haghikia
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Gut Microbiome ◽  
Human Life ◽  
Microbiome Composition ◽  
Immune Mediated ◽  
The Central Nervous System ◽  
The Impact ◽  
The Relationship

Within the last century, human lifestyle and dietary behaviors have changed dramatically. These changes, especially concerning hygiene, have led to a marked decrease in some diseases, i.e., infectious diseases. However, other diseases that can be attributed to the so-called ‘Western’ lifestyle have increased, i.e., metabolic and cardiovascular disorders. More recently, multifactorial disorders, such as autoimmune and neurodegenerative diseases, have been associated with changes in diet and the gut microbiome. In particular, short chain fatty acid (SCFA)-producing bacteria are of high interest. SCFAs are the main metabolites produced by bacteria and are often reduced in a dysbiotic state, causing an inflammatory environment. Based on advanced technologies, high-resolution investigations of the abundance and composition of the commensal microbiome are now possible. These techniques enable the assessment of the relationship between the gut microbiome, its metabolome and gut-associated immune and neuronal cells. While a growing number of studies have shown the indirect impact of gut metabolites, mediated by alterations of immune-mediated mechanisms, the direct influence of these compounds on cells of the central nervous system needs to be further elucidated. For instance, the SCFA propionic acid (PA) increases the amount of intestine-derived regulatory T cells, which furthermore can positively affect the central nervous system (CNS), e.g., by increasing remyelination. However, the question of if and how PA can directly interact with CNS-resident cells is a matter of debate. In this review, we discuss the impact of an altered microbiome composition in relation to various diseases and discuss how the commensal microbiome is shaped, starting from the beginning of human life.

scholarly journals Gut microbiome signatures of risk and prodromal markers of Parkinson’s disease

2019 ◽  
Author(s):  
Sebastian Heinzel ◽  
Velma T. E. Aho ◽  
Ulrike Suenkel ◽  
Anna-Katharina von Thaler ◽  
Claudia Schulte ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiome ◽  
Physical Inactivity ◽  
Disease Onset ◽  
Rem Sleep Behavior Disorder ◽  
Sleep Behavior ◽  
Microbiome Composition ◽  
Β Diversity ◽  
The Impact

AbstractObjectivesAlterations of the gut microbiome in Parkinson’s disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they may be related to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition.MethodsEstablished risk and prodromal markers of PD as well as factors related to diet/lifestyle, bowel function and medication were studied in relation to bacterial α-/β-diversity, enterotypes, and taxonomic composition in stool samples of 666 elderly TREND study participants.ResultsAmong risk and prodromal markers, physical inactivity, constipation and age showed associations with α- and β-diversity, and for both measures subthreshold parkinsonism and physical inactivity showed interaction effects. Moreover, male sex, possible REM-sleep behavior disorder (RBD), smoking as well as body-mass-index, antidiabetic and urate-lowering medication were associated with β-diversity. Physical inactivity and constipation severity were increased in individuals with the Firmicutes-enriched enterotype. Subthreshold parkinsonism was least frequently observed in individuals with the Prevotella-enriched enterotype. Differentially abundant taxa were linked to constipation, physical inactivity, possible RBD, and subthreshold parkinsonism. Substantia nigra hyperechogenicity, olfactory loss, depression, orthostatic hypotension, urinary/erectile dysfunction, PD family history and the overall prodromal PD probability showed no significant microbiome associations.InterpretationSeveral risk and prodromal markers of PD are associated with changes in gut microbiome composition. However, the impact of the gut microbiome on PD risk and potential microbiome-dependent subtypes in the prodrome of PD need further investigation based on prospective clinical and (multi)omics data in incident PD cases.

scholarly journals Lacticaseibacillus rhamnosus GG and Saccharomyces cerevisiae boulardii supplementation exert protective effects on human gut microbiome following antibiotic administration in vitro

2021 ◽  
pp. 1-16
Author(s):  
C. Duysburgh ◽  
P. Van den Abbeele ◽  
M. Morera ◽  
M. Marzorati
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Gut Microbiome ◽  
Gastrointestinal Symptoms ◽  
Lactobacillus Rhamnosus ◽  
Antibiotic Administration ◽  
Protective Effects ◽  
Human Gut ◽  
Human Gut Microbiome ◽  
The Impact

Antibiotic-induced dysbiosis of the microbial community has been associated with several gastrointestinal symptoms. The impact of repeated administration of Lacticaseibacillus rhamnosus GG (CNCM-I-4798) (formerly known as Lactobacillus rhamnosus GG), Saccharomyces cerevisiae boulardii (CNCM-I-1079) and their combination (associated in Smebiocta/Smectaflora Protect®) in supporting recovery of gut microbiota functionality and composition during and following amoxicillin:clavulanic acid administration was evaluated in vitro. Antibiotic dosage negatively affected SCFA production, coinciding with detrimental effects on Bacteroidetes, Firmicutes and Bifidobacterium spp. in the simulated proximal colon, while Akkermansia muciniphila was significantly reduced in the distal colon. L. rhamnosus GG and S. boulardii were able to thrive in both colon regions upon dosing, with S. boulardii even showing protective effects on the survival of L. rhamnosus GG during antibiotic administration. The impact of the probiotic strains on microbiome recovery revealed that supplementation with L. rhamnosus GG and/or S. boulardii resulted in a stimulating effect on the most abundant bacterial groups within the bacterial community of each donor. For one of the donors tested, co-dosing of L. rhamnosus GG and S. boulardii resulted in superior short-chain fatty acid recovery accompanied by a stronger increase in abundance of Bifidobacteriaceae. Overall, the current study provides first evidence that combined supplementation of L. rhamnosus GG and S. boulardii might be an interesting candidate in limiting detrimental effects of amoxicillin:clavulanic acid on the human gut microbiome, though further studies are warranted to confirm these findings.

scholarly journals Hyperoxia Provokes Time- and Dose-Dependent Gut Injury and Endotoxemia and Alters Gut Microbiome and Transcriptome in Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Yunhang Li ◽  
Yuanfa Tao ◽  
Jingyu Xu ◽  
Yihuai He ◽  
Wen Zhang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Transcriptome Analysis ◽  
Gut Microbiome ◽  
Control Group ◽  
Dependent Manner ◽  
Barrier Dysfunction ◽  
Necrosis Factor Alpha ◽  
Gut Dysbiosis ◽  
The Impact ◽  
Dose Dependent

Background: Oxygen therapy usually exposes patients to hyperoxia, which induces injuries in the lung, the heart, and the brain. The gut and its microbiome play key roles in critical illnesses, but the impact of hyperoxia on the gut and its microbiome remains not very clear. We clarified the time- and dose-dependent effects of hyperoxia on the gut and investigated oxygen-induced gut dysbiosis and explored the underlying mechanism of gut injury by transcriptome analysis.Methods: The C57BL/6 mice were randomly divided into the control group and nine different oxygen groups exposed to hyperoxia with an inspired O2 fraction (FiO2) of 40, 60, and 80% for 24, 72, and 168 h (7 days), respectively. Intestinal histopathological and biochemical analyses were performed to explore the oxygen-induced gut injury and inflammatory response. Another experiment was performed to explore the impact of hyperoxia on the gut microbiome by exposing the mice to hyperoxia (FiO2 80%) for 7 days, with the 16S rRNA sequencing method. We prolonged the exposure (up to 14 days) of the mice to hyperoxia (FiO2 80%), and gut transcriptome analysis and western blotting were carried out to obtain differentially expressed genes (DEGs) and signaling pathways related to innate immunity and cell death.Results: Inhaled oxygen induced time- and dose-dependent gut histopathological impairment characterized by mucosal atrophy (e.g., villus shortening: 80% of FiO2 for 24 h: P = 0.008) and enterocyte death (e.g., apoptosis: 40% of FiO2 for 7 days: P = 0.01). Administered time- and dose-dependent oxygen led to intestinal barrier dysfunction (e.g., endotoxemia: 80% of FiO2 for 72 h: P = 0.002) and potentiated gut inflammation by increasing proinflammatory cytokines [e.g., tumor necrosis factor alpha (TNF-α): 40% of FiO2 for 24 h: P = 0.003)] and reducing anti-inflammatory cytokines [Interleukin 10 (IL-10): 80% of FiO2 for 72 h: P < 0.0001]. Hyperoxia induced gut dysbiosis with an expansion of oxygen-tolerant bacteria (e.g., Enterobacteriaceae). Gut transcriptome analysis identified 1,747 DEGs and 171 signaling pathways and immunoblotting verified TLR-4, NOD-like receptor, and apoptosis signaling pathways were activated in oxygen-induced gut injury.Conclusions: Acute hyperoxia rapidly provokes gut injury in a time- and dose-dependent manner and induces gut dysbiosis, and an innate immune response is involved in an oxygen-induced gut injury.

The Impact of Natural Compounds on the Treatment of Neurodegenerative Diseases

2019 ◽  
Vol 23 (3) ◽  
pp. 335-360 ◽  
Author(s):  
Lorane I. da S. Hage-Melim ◽  
Jaderson V. Ferreira ◽  
Nayana K.S. de Oliveira ◽  
Lenir C. Correia ◽  
Marcos R.S. Almeida ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Muscular Atrophy ◽  
Neuronal Loss ◽  
The Elderly ◽  
Natural Compounds ◽  
Drug Candidates ◽  
Jakob Disease ◽  
The Central Nervous System ◽  
The Impact

Neurodegenerative diseases (NDDs) are characterized by a progressive deterioration of the motor and/or cognitive function, that are often accompanied by psychiatric disorders, caused by a selective loss of neurons in the central nervous system. Among the NDDs we can mention Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia 3 (SCA3), spinal and bulbar muscular atrophy (SBMA) and Creutzfeldt-Jakob disease (CJD). AD and HD are characterized mainly by massive neuronal loss. PD, ALS, SCA3 and SBMA are agerelated diseases which have characteristic motor symptoms. CJD is an NDD caused by prion proteins. With increasing life expectancy, elderly populations tend to have more health problems, such as chronic diseases related to age and disability. Therefore, the development of therapeutic strategies to treat or prevent multiple pathophysiological conditions in the elderly can improve the expectation and quality of life. The attention of researchers has been focused on bioactive natural compounds that represent important resources in the discovery and development of drug candidates against NDDs. In this review, we discuss the pathogenesis, symptoms, potential targets, treatment and natural compounds effective in the treatment of AD, PD, HD, ALS, SCA3, SBMA and CJD.

scholarly journals The impact of epigenetics on the development of neurodegenerative diseases

2021 ◽  
Author(s):  
Gustavo Hugo de Souza Faria
Keyword(s):  
Dna Methylation ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Disease Onset ◽  
Specific Protein ◽  
Aberrant Methylation ◽  
Transcriptional Dysregulation ◽  
Altered Gene ◽  
The Impact

Introduction: Neurodegenerative diseases affect thousands of people in Brazil and have been increasing in frequency with the aging population. However, little is known about the molecular mechanisms and biomarkers of these diseases, which leads to a medical approach based on symptomatic and unresolving characteristics. Epigenetics, including DNA methylation, histone modifications, and changes in regulatory RNAs, emerges as a tool for prevention of neurodegenerative diseases. Objectives: To review studies that discuss the role of epigenetics in the development of neurodegenerative diseases. Methodology: This study involved an integrative review of papers published from 2016 to 2021 by searching PubMed and Scopus. Results: The studies showed that there is evidence that epigenetic mechanisms interfere with the development of major neurodegenerative diseases. Huntington’s disease presents an altered gene from birth, but transcriptional dysregulation is characteristic of the pathology that may be correlated to the age of disease onset in the cortex. In Parkinson’s disease dysregulation of expression of a specific protein is believed to play a central role in the disease and occurs through aberrant methylation that controls activation or suppression. In relation to Alzheimer’s disease, it has been found that deregulated DNA methylation and demethylation is linked to the onset and progression of the disease. In addition, these epigenetic factors are interfered with by diet, aging, and exercise. Conclusions: Investment in epigenetic studies is needed to understand possible markers of neurodegenerative diseases, for early diagnosis and the formation of epidrugs with the ability to treat.

scholarly journals Gut dysbiosis breaks immunological tolerance toward the central nervous system during young adulthood

2017 ◽  
Vol 114 (44) ◽  
pp. E9318-E9327 ◽  
Author(s):  
Sudhir K. Yadav ◽  
Sridhar Boppana ◽  
Naoko Ito ◽  
John E. Mindur ◽  
Martin T. Mathay ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Young Adulthood ◽  
Disease Onset ◽  
Immunological Tolerance ◽  
Complement C3 ◽  
Gut Dysbiosis ◽  
Cns Autoimmunity ◽  
The Central Nervous System ◽  
Anaphylatoxin C3a

Multiple sclerosis (MS) is an autoimmune disease targeting the central nervous system (CNS) mainly in young adults, and a breakage of immune tolerance to CNS self-antigens has been suggested to initiate CNS autoimmunity. Age and microbial infection are well-known factors involved in the development of autoimmune diseases, including MS. Recent studies have suggested that alterations in the gut microbiota, referred to as dysbiosis, are associated with MS. However, it is still largely unknown how gut dysbiosis affects the onset and progression of CNS autoimmunity. In this study, we investigated the effects of age and gut dysbiosis on the development of CNS autoimmunity in humanized transgenic mice expressing the MS-associated MHC class II (MHC-II) gene, HLA-DR2a, and T-cell receptor (TCR) genes specific for MBP87-99/DR2a that were derived from an MS patient. We show here that the induction of gut dysbiosis triggers the development of spontaneous experimental autoimmune encephalomyelitis (EAE) during adolescence and early young adulthood, while an increase in immunological tolerance with aging suppresses disease onset after late young adulthood in mice. Furthermore, gut dysbiosis induces the expression of complement C3 and production of the anaphylatoxin C3a, and down-regulates the expression of the Foxp3 gene and anergy-related E3 ubiquitin ligase genes. Consequently, gut dysbiosis was able to trigger the development of encephalitogenic T cells and promote the induction of EAE during the age window of young adulthood.

scholarly journals Gut microbial signature and gut-lung axis: A possible role in the therapy of COVID-19

Bioimpacts ◽  
2021 ◽  
Author(s):  
Ata Mahmoodpoor ◽  
Ali Shamekh ◽  
Sarvin Sanaie
Keyword(s):  
Gut Microbiota ◽  
Immune Responses ◽  
Prognostic Marker ◽  
Gut Microbiome ◽  
Viral Infections ◽  
Nutrition Therapy ◽  
Host Defenses ◽  
Personalized Nutrition ◽  
Gut Dysbiosis ◽  
The Impact

The impact of gut as the origin of different disorders has led to the "gut-origin concept" of diseases. The gut microbiome regulates host defenses against viral infections, thus dysbiosis can play a major role in triggering the cascade of inflammation and causing immune imbalances in COVID-19 patients. It appears that gut microbial signature in COVID-19 patients can be used as a potential diagnostic, therapeutic, and even a prognostic marker. Personalized nutrition therapy can be used by profiling the gut microbiota of individual patients and specialized probiotics/synbiotics to modify gut dysbiosis. Hence, improving overall immune responses can be recommended in these patients.

scholarly journals Towards Tailored Gut Microbiome-Based and Dietary Interventions for Promoting the Development and Maintenance of a Healthy Brain

2021 ◽  
Vol 9 ◽  
Author(s):  
Ana Larroya ◽  
Jorge Pantoja ◽  
Pilar Codoñer-Franch ◽  
María Carmen Cenit
Keyword(s):  
Mental Health ◽  
Gut Microbiota ◽  
Brain Development ◽  
Gut Microbiome ◽  
Dietary Interventions ◽  
Complex Interplay ◽  
Ongoing Research ◽  
Long Term Consequences ◽  
The Impact

Mental health is determined by a complex interplay between the Neurological Exposome and the Human Genome. Multiple genetic and non-genetic (exposome) factors interact early in life, modulating the risk of developing the most common complex neurodevelopmental disorders (NDDs), with potential long-term consequences on health. To date, the understating of the precise etiology underpinning these neurological alterations, and their clinical management pose a challenge. The crucial role played by diet and gut microbiota in brain development and functioning would indicate that modulating the gut-brain axis may help protect against the onset and progression of mental-health disorders. Some nutritional deficiencies and gut microbiota alterations have been linked to NDDs, suggesting their potential pathogenic implications. In addition, certain dietary interventions have emerged as promising alternatives or adjuvant strategies for improving the management of particular NDDs, at least in particular subsets of subjects. The gut microbiota can be a key to mediating the effects of other exposome factors such as diet on mental health, and ongoing research in Psychiatry and Neuropediatrics is developing Precision Nutrition Models to classify subjects according to a diet response prediction based on specific individual features, including microbiome signatures. Here, we review current scientific evidence for the impact of early life environmental factors, including diet, on gut microbiota and neuro-development, emphasizing the potential long-term consequences on health; and also summarize the state of the art regarding the mechanisms underlying diet and gut microbiota influence on the brain–gut axis. Furthermore, we describe the evidence supporting the key role played by gut microbiota, diet and nutrition in neurodevelopment, as well as the effectiveness of certain dietary and microbiome-based interventions aimed at preventing or treating NDDs. Finally, we emphasize the need for further research to gain greater insight into the complex interplay between diet, gut microbiome and brain development. Such knowledge would help towards achieving tailored integrative treatments, including personalized nutrition.

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