Modification of the gut microbiome to combat neurodegeneration

2019 ◽  
Vol 30 (8) ◽  
pp. 795-805 ◽  
Author(s):  
Andrew Octavian Sasmita
Keyword(s):  
Neurodegenerative Diseases ◽  
Gut Microbiome ◽  
Neurological Disorders ◽  
Potential Role ◽  
Fecal Microbiota ◽  
Gi Tract ◽  
Specific Context ◽  
Fecal Microbiota Transplant ◽  
Immense Potential ◽  
Lateral Sclerosis

Abstract The gut microbiome was extensively researched for its biological variety and its potential role in propagating diseases outside of the gastrointestinal (GI) tract. Recently, a lot of effort was focused on comprehending the gut-brain axis and the bizarre communication between the GI system and the nervous system. Ample amount of studies being carried out also revealed the involvement of the gut microbiome in enhancing the degree of many neurological disorders, including neurodegenerative diseases. It was widely observed that there were distinct microbiome profiles and dysbiosis within patients suffering from Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. Various approaches to re-establish the balance of the gut microbiome, from antibiotic therapy, fecal microbiota transplant, or ingestion of psychobiotics, are discussed within this review within the specific context of combating neurodegenerative diseases. Present studies and clinical trials indicate that although there is an immense potential of gut microbiome modification to be preventive or therapeutic, there are still many intercalated components of the gut-brain axis at play and thus, more research needs to be carried out to delineate microbiome factors that may potentially alleviate symptoms of neurodegeneration.

scholarly journals Effect of Fecal Microbiota Transplant on Symptoms of Psychiatric Disorders: A Systematic Review

2020 ◽  
Author(s):  
Arthi Chinna Meyyappan ◽  
Evan Forth ◽  
Caroline Wallace ◽  
Roumen Milev
Keyword(s):  
Fecal Microbiota ◽  
Efficacy And Safety ◽  
Gi Tract ◽  
Eligibility Criteria ◽  
Fecal Microbiota Transplant ◽  
Psychiatric Illnesses ◽  
Bidirectional Signaling ◽  
Key Terms ◽  
The Brain ◽  
Larger Sample

Abstract Background: The Gut-Brain-Axis is a bidirectional signaling pathway between the gastrointestinal (GI) tract and the brain. The hundreds of trillions of microorganisms populating the gastrointestinal tract are thought to modulate this connection, and have far reaching effects on the immune system, central and autonomic nervous systems, and GI functioning. These interactions have also been linked to various psychiatric illnesses such as depression, anxiety, substance abuse, and eating disorders. It is hypothesized that techniques aimed at strengthening and repopulating the gut microbiome, such as Fecal Microbiota Transplant (FMT), may be useful in the prevention and treatment of psychiatric illnesses. Methods: A systematic search of five databases was conducted using key terms related to FMT and psychiatric illnesses. All results were then evaluated based on specific eligibility criteria. Results: Twenty-one studies met the eligibility criteria and were analysed for reported changes in mood and behavioural measures indicative of psychiatric wellbeing. The studies included were either entirely clinical (n=7), preclinical with human donors (n=7), or entirely preclinical (n=7). All studies found a decrease in depressive and anxiety-like symptoms and behaviours resulting from the transplantation of healthy microbiota. The inverse was also found, with the transmission of depressive and anxiety-like symptoms and behaviours resulting from the transplantation of microbiota from psychiatrically ill donors to healthy recipients. Conclusion: There appears to be strong evidence for the treatment and transmission of psychiatric illnesses through FMT. Further research with larger sample sizes and stronger scientific design is warranted in order to fully determine the efficacy and safety of this potential treatment.

The Influence of Vitamin D on Neurodegeneration and Neurological Disorders: A Rationale for its Physio-pathological Actions

2020 ◽  
Vol 26 (21) ◽  
pp. 2475-2491 ◽  
Author(s):  
Maria Morello ◽  
Massimo Pieri ◽  
Rossella Zenobi ◽  
Alessandra Talamo ◽  
Delphine Stephan ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Steroid Hormone ◽  
Neuroactive Steroid ◽  
Brain Functions ◽  
Prevention And Treatment ◽  
Lateral Sclerosis

Vitamin D is a steroid hormone implicated in the regulation of neuronal integrity and many brain functions. Its influence, as a nutrient and a hormone, on the physiopathology of the most common neurodegenerative diseases is continuously emphasized by new studies. This review addresses what is currently known about the action of vitamin D on the nervous system and neurodegenerative diseases such as Multiple Sclerosis, Alzheimer’s disease, Parkinson’s disease and Amyotrophic Lateral Sclerosis. Further vitamin D research is necessary to understand how the action of this “neuroactive” steroid can help to optimize the prevention and treatment of several neurological diseases.

scholarly journals A Sex Perspective in Neurodegenerative Diseases: microRNAs as Possible Peripheral Biomarkers

2021 ◽  
Vol 22 (9) ◽  
pp. 4423
Author(s):  
Paola Piscopo ◽  
Maria Bellenghi ◽  
Valeria Manzini ◽  
Alessio Crestini ◽  
Giada Pontecorvi ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Significant Variable ◽  
Patient Stratification ◽  
Literature Analysis ◽  
Therapeutic Approaches ◽  
Males And Females ◽  
Near Future ◽  
Future Patient ◽  
Lateral Sclerosis

Sex is a significant variable in the prevalence and incidence of neurological disorders. Sex differences exist in neurodegenerative disorders (NDs), where sex dimorphisms play important roles in the development and progression of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. In the last few years, some sex specific biomarkers for the identification of NDs have been described and recent studies have suggested that microRNA (miRNA) could be included among these, as influenced by the hormonal and genetic background. Failing to consider the possible differences between males and females in miRNA evaluation could introduce a sex bias in studies by not considering some of these sex-related biomarkers. In this review, we recapitulate what is known about the sex-specific differences in peripheral miRNA levels in neurodegenerative diseases. Several studies have reported sex-linked disparities, and from the literature analysis miR-206 particularly has been shown to have a sex-specific involvement. Hopefully, in the near future, patient stratification will provide important additional clues in diagnosis, prognosis, and tailoring of the best therapeutic approaches for each patient. Sex-specific biomarkers, such as miRNAs, could represent a useful tool for characterizing subgroups of patients.

scholarly journals Effects of dietary restriction on neuroinflammation in neurodegenerative diseases

2021 ◽  
Vol 218 (2) ◽  
Author(s):  
Luigi Fontana ◽  
Laura Ghezzi ◽  
Anne H. Cross ◽  
Laura Piccio
Keyword(s):  
Neurodegenerative Diseases ◽  
Gut Microbiome ◽  
Food Restriction ◽  
Brain Aging ◽  
Cellular Tissue ◽  
Calorie Intake ◽  
Normal Brain ◽  
Meal Frequency ◽  
Peripheral Metabolism ◽  
Lateral Sclerosis

Recent and accumulating work in experimental animal models and humans shows that diet has a much more pervasive and prominent role than previously thought in modulating neuroinflammatory and neurodegenerative mechanisms leading to some of the most common chronic central nervous system (CNS) diseases. Chronic or intermittent food restriction has profound effects in shaping brain and peripheral metabolism, immunity, and gut microbiome biology. Interactions among calorie intake, meal frequency, diet quality, and the gut microbiome modulate specific metabolic and molecular pathways that regulate cellular, tissue, and organ homeostasis as well as inflammation during normal brain aging and CNS neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis, among others. This review discusses these findings and their potential application to the prevention and treatment of CNS neuroinflammatory diseases and the promotion of healthy brain aging.

scholarly journals Phages in the Gut Ecosystem

2022 ◽  
Vol 11 ◽  
Author(s):  
Michele Zuppi ◽  
Heather L. Hendrickson ◽  
Justin M. O’Sullivan ◽  
Tommi Vatanen
Keyword(s):  
Gut Microbiome ◽  
Well Being ◽  
Gastrointestinal Diseases ◽  
Fecal Microbiota ◽  
Ecosystem Dynamics ◽  
Bacterial Survival ◽  
Human Immune System ◽  
Fecal Microbiota Transplant ◽  
Bacterial Fitness ◽  
Biological Entities

Phages, short for bacteriophages, are viruses that specifically infect bacteria and are the most abundant biological entities on earth found in every explored environment, from the deep sea to the Sahara Desert. Phages are abundant within the human biome and are gaining increasing recognition as potential modulators of the gut ecosystem. For example, they have been connected to gastrointestinal diseases and the treatment efficacy of Fecal Microbiota Transplant. The ability of phages to modulate the human gut microbiome has been attributed to the predation of bacteria or the promotion of bacterial survival by the transfer of genes that enhance bacterial fitness upon infection. In addition, phages have been shown to interact with the human immune system with variable outcomes. Despite the increasing evidence supporting the importance of phages in the gut ecosystem, the extent of their influence on the shape of the gut ecosystem is yet to be fully understood. Here, we discuss evidence for phage modulation of the gut microbiome, postulating that phages are pivotal contributors to the gut ecosystem dynamics. We therefore propose novel research questions to further elucidate the role(s) that they have within the human ecosystem and its impact on our health and well-being.

scholarly journals Microbiome–microglia connections via the gut–brain axis

2018 ◽  
Vol 216 (1) ◽  
pp. 41-59 ◽  
Author(s):  
Reem Abdel-Haq ◽  
Johannes C.M. Schlachetzki ◽  
Christopher K. Glass ◽  
Sarkis K. Mazmanian
Keyword(s):  
Immune Cells ◽  
Gut Microbiome ◽  
Neurological Disorders ◽  
Microbial Community Composition ◽  
Future Research ◽  
Gi Tract ◽  
Synaptic Remodeling ◽  
And Function ◽  
The Brain ◽  
Microglial Development

Microglia, the resident immune cells in the brain, are essential for modulating neurogenesis, influencing synaptic remodeling, and regulating neuroinflammation by surveying the brain microenvironment. Microglial dysfunction has been implicated in the onset and progression of several neurodevelopmental and neurodegenerative diseases; however, the multitude of factors and signals influencing microglial activity have not been fully elucidated. Microglia not only respond to local signals within the brain but also receive input from the periphery, including the gastrointestinal (GI) tract. Recent preclinical findings suggest that the gut microbiome plays a pivotal role in regulating microglial maturation and function, and altered microbial community composition has been reported in neurological disorders with known microglial involvement in humans. Collectively, these findings suggest that bidirectional crosstalk between the gut and the brain may influence disease pathogenesis. Herein, we discuss recent studies showing a role for the gut microbiome in modulating microglial development and function in homeostatic and disease conditions and highlight possible future research to develop novel microbial treatments for disorders of the brain.

scholarly journals Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients

Science ◽  
2021 ◽  
Vol 371 (6529) ◽  
pp. 595-602 ◽  
Author(s):  
Diwakar Davar ◽  
Amiran K. Dzutsev ◽  
John A. McCulloch ◽  
Richard R. Rodrigues ◽  
Joe-Marc Chauvin ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
T Cell Activation ◽  
Gut Microbiome ◽  
Cell Activation ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Advanced Melanoma ◽  
Fecal Microbiota Transplant ◽  
Network Analyses ◽  
Clinical Benefits

Anti–programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti–PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti–PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti–PD-1 in patients with PD-1–refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation. Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti–PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8–expressing myeloid cells. Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes. Collectively, our findings show that FMT and anti–PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti–PD-1 in a subset of PD-1 advanced melanoma.

scholarly journals Stronger connectivity of the resident gut microbiome lends resistance to invading bacteria

2018 ◽  
Author(s):  
Cristina M. Herren ◽  
Michael Baym
Keyword(s):  
Gut Microbiome ◽  
Human Subjects ◽  
Bacterial Community Composition ◽  
Biotic Interactions ◽  
Simulation Models ◽  
Fecal Microbiota ◽  
Colonization Resistance ◽  
Community Members ◽  
Fecal Microbiota Transplant ◽  
Invasive Taxa

AbstractBacterial infection in the gut is often due to successful invasion of the host microbiome by an introduced pathogen. Ecological theory indicates that resident community members and their interactions should be strong determinants of whether an invading taxon can persist in a community. In the context of the gut microbiome, this suggests colonization resistance against newly introduced bacteria should depend on the instantaneous bacterial community composition within the gut and interactions between these constituent members. Here we develop a mathematical model of how metabolite-dependent biotic interactions between resident bacteria mediate invasion, and find that stronger biotic connectivity from metabolite cross-feeding and competition increases colonization resistance. We then introduce a statistical method for identifying invasive taxa in the human gut, and show empirically that greater connectivity of the resident gut microbiome is related to increased resistance to invading bacteria. Finally, we examined patient outcomes after fecal microbiota transplant (FMT) for recurring Clostridium difficile infection. Patients with lower connectivity of the gut microbiome after treatment were more likely to relapse, experiencing a later infection. Thus, simulation models and data from human subjects support the hypothesis that stronger interactions between bacteria in the gut repel invaders. These results demonstrate how ecological invasion theory can be applied to the gut microbiome, which might inform targeted microbiome manipulations and interventions. More broadly, this study provides evidence that low connectivity in gut microbial communities is a hallmark of community instability and susceptibility to invasion.

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