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Journal ArticleDOI

Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis.

TL;DR: The biological interplay between gut-brain axis is discussed, and how this communication may be dysregulated in neurological diseases is explored, and new insights in modification of gut microbiota composition are highlighted.
Abstract: Development of central nervous system (CNS) is regulated by both intrinsic and peripheral signals. Previous studies have suggested that environmental factors affect neurological activities under both physiological and pathological conditions. Although there is anatomical separation, emerging evidence has indicated the existence of bidirectional interaction between gut microbiota, i.e., (diverse microorganisms colonizing human intestine), and brain. The cross-talk between gut microbiota and brain may have crucial impact during basic neurogenerative processes, in neurodegenerative disorders and tumors of CNS. In this review, we discuss the biological interplay between gut-brain axis, and further explore how this communication may be dysregulated in neurological diseases. Further, we highlight new insights in modification of gut microbiota composition, which may emerge as a promising therapeutic approach to treat CNS disorders.

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Citations
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TL;DR: The prevailing data suggest that micro- and nanoplastic accumulation in mammalian and human tissues would likely have negative, yet unclear long-term consequences, and there is a need for cellular and systemic toxicity due to micro-and nanoplastics to be better illuminated, and the underlying mechanisms defined by further work.
Abstract: Fragmented or otherwise miniaturized plastic materials in the form of micro- or nanoplastics have been of nagging environmental concern. Perturbation of organismal physiology and behavior by micro- and nanoplastics have been widely documented for marine invertebrates. Some of these effects are also manifested by larger marine vertebrates such as fishes. More recently, possible effects of micro- and nanoplastics on mammalian gut microbiota as well as host cellular and metabolic toxicity have been reported in mouse models. Human exposure to micro- and nanoplastics occurs largely through ingestion, as these are found in food or derived from food packaging, but also in a less well-defined manner though inhalation. The pathophysiological consequences of acute and chronic micro- and nanoplastics exposure in the mammalian system, particularly humans, are yet unclear. In this review, we focus on the recent findings related to the potential toxicity and detrimental effects of micro- and nanoplastics as demonstrated in mouse models as well as human cell lines. The prevailing data suggest that micro- and nanoplastics accumulation in mammalian and human tissues would likely have negative, yet unclear long-term consequences. There is a need for cellular and systemic toxicity due to micro- and nanoplastics to be better illuminated, and the underlying mechanisms defined by further work.

375 citations

Journal ArticleDOI
TL;DR: The status of the knowledge and the open questions in the field focusing on the function of intestinal microbial metabolites or products on CNS cells during healthy and inflammatory conditions, such as multiple sclerosis, Alzheimer's and Parkinson’s diseases, and also neuropsychiatric disorders are discussed.
Abstract: The human microbiota has a fundamental role in host physiology and pathology. Gut microbial alteration, also known as dysbiosis, is a condition associated not only with gastrointestinal disorders but also with diseases affecting other distal organs. Recently it became evident that the intestinal bacteria can affect the central nervous system (CNS) physiology and inflammation. The nervous system and the gastrointestinal tract are communicating through a bidirectional network of signaling pathways called the gut-brain axis, which consists of multiple connections, including the vagus nerve, the immune system, and bacterial metabolites and products. During dysbiosis, these pathways are dysregulated and associated with altered permeability of the blood-brain barrier (BBB) and neuroinflammation. However, numerous mechanisms behind the impact of the gut microbiota in neuro-development and -pathogenesis remain poorly understood. There are several immune pathways involved in CNS homeostasis and inflammation. Among those, the inflammasome pathway has been linked to neuroinflammatory conditions such as multiple sclerosis, Alzheimer's and Parkinson's diseases, but also anxiety and depressive-like disorders. The inflammasome complex assembles upon cell activation due to exposure to microbes, danger signals, or stress and lead to the production of pro-inflammatory cytokines (interleukin-1β and interleukin-18) and to pyroptosis. Evidences suggest that there is a reciprocal influence of microbiota and inflammasome activation in the brain. However, how this influence is precisely working is yet to be discovered. Herein, we discuss the status of the knowledge and the open questions in the field focusing on the function of intestinal microbial metabolites or products on CNS cells during healthy and inflammatory conditions, such as multiple sclerosis, Alzheimer's and Parkinson's diseases, and also neuropsychiatric disorders. In particular, we focus on the innate inflammasome pathway as immune mechanism that can be involved in several of these conditions, upon exposure to certain microbes.

229 citations

Journal ArticleDOI
TL;DR: As aging together with poor diet and gut-derived inflammatory response due to dysbiosis contributes to the pathogenesis of AD, modification of gut microbial composition by uptake of probiotic-rich food can act as a preventive/therapeutic option for AD.

165 citations

Journal ArticleDOI
09 Aug 2019-Cells
TL;DR: Both benefits and pitfalls of molecular biology and proteomics analyses are discussed, including the different mass spectrometry-based analytical techniques, highlighting how these investigation strategies are powerful tools to study the biology of glioblastoma, as well as to develop advanced methods for the management of this pathology.
Abstract: Glioblastoma multiforme is the most aggressive malignant tumor of the central nervous system. Due to the absence of effective pharmacological and surgical treatments, the identification of early diagnostic and prognostic biomarkers is of key importance to improve the survival rate of patients and to develop new personalized treatments. On these bases, the aim of this review article is to summarize the current knowledge regarding the application of molecular biology and proteomics techniques for the identification of novel biomarkers through the analysis of different biological samples obtained from glioblastoma patients, including DNA, microRNAs, proteins, small molecules, circulating tumor cells, extracellular vesicles, etc. Both benefits and pitfalls of molecular biology and proteomics analyses are discussed, including the different mass spectrometry-based analytical techniques, highlighting how these investigation strategies are powerful tools to study the biology of glioblastoma, as well as to develop advanced methods for the management of this pathology.

147 citations


Cites background from "Impact of microbiota on central ner..."

  • ...Recently, different reports have described the existence of a so called “gut-brain axis”, showing that the dysregulation of the gut microbiota may lead to the alterations of several processes predisposing to the development of a number of nervous system diseases, including cancer [61,62]....

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Journal ArticleDOI
TL;DR: Bacterial metabolites with known or suspected neuromodulatory activity are described, mechanisms of signalling pathways from the gut microbiota to the brain are defined and direct effects that gut bacterial molecules are likely exerting on specific brain cells are discussed.
Abstract: Mounting evidence suggests that the gut microbiome impacts brain development and function. Gut-brain connections may be mediated by an assortment of microbial molecules that are produced in the gastrointestinal tract, which can subsequently permeate many organs, including sometimes the brain. Studies in animal models have identified molecular cues propagated from intestinal bacteria to the brain that can affect neurological function and/or neurodevelopmental and neurodegenerative conditions. Herein, we describe bacterial metabolites with known or suspected neuromodulatory activity, define mechanisms of signalling pathways from the gut microbiota to the brain and discuss direct effects that gut bacterial molecules are likely exerting on specific brain cells. Many discoveries are recent, and the findings described in this Perspective are largely novel and yet to be extensively validated. However, expanding research into the dynamic molecular communications between gut microorganisms and the CNS continues to uncover critical and previously unappreciated clues in understanding the pathophysiology of behavioural, psychiatric and neurodegenerative diseases.

136 citations

References
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Journal ArticleDOI
TL;DR: The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations, permitting the differentiation of six stages.
Abstract: Eighty-three brains obtained at autopsy from nondemented and demented individuals were examined for extracellular amyloid deposits and intraneuronal neurofibrillary changes. The distribution pattern and packing density of amyloid deposits turned out to be of limited significance for differentiation of neuropathological stages. Neurofibrillary changes occurred in the form of neuritic plaques, neurofibrillary tangles and neuropil threads. The distribution of neuritic plaques varied widely not only within architectonic units but also from one individual to another. Neurofibrillary tangles and neuropil threads, in contrast, exhibited a characteristic distribution pattern permitting the differentiation of six stages. The first two stages were characterized by an either mild or severe alteration of the transentorhinal layer Pre-alpha (transentorhinal stages I-II). The two forms of limbic stages (stages III-IV) were marked by a conspicuous affection of layer Pre-alpha in both transentorhinal region and proper entorhinal cortex. In addition, there was mild involvement of the first Ammon's horn sector. The hallmark of the two isocortical stages (stages V-VI) was the destruction of virtually all isocortical association areas. The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations.

13,699 citations

Journal ArticleDOI

8,941 citations

Journal ArticleDOI
10 Apr 1992-Science
TL;DR: An extensive catalog of genes that act in a migrating cell is provided, unique molecular functions involved in nematode cell migration are identified, and similar functions in humans are suggested.
Abstract: In both metazoan development and metastatic cancer, migrating cells must carry out a detailed, complex program of sensing cues, binding substrates, and moving their cytoskeletons. The linker cell in Caenorhabditis elegans males undergoes a stereotyped migration that guides gonad organogenesis, occurs with precise timing, and requires the nuclear hormone receptor NHR-67. To better understand how this occurs, we performed RNA-seq of individually staged and dissected linker cells, comparing transcriptomes from linker cells of third-stage (L3) larvae, fourth-stage (L4) larvae, and nhr-67-RNAi–treated L4 larvae. We observed expression of 8,000–10,000 genes in the linker cell, 22–25% of which were up- or down-regulated 20-fold during development by NHR-67. Of genes that we tested by RNAi, 22% (45 of 204) were required for normal shape and migration, suggesting that many NHR-67–dependent, linker cell-enriched genes play roles in this migration. One unexpected class of genes up-regulated by NHR-67 was tandem pore potassium channels, which are required for normal linker-cell migration. We also found phenotypes for genes with human orthologs but no previously described migratory function. Our results provide an extensive catalog of genes that act in a migrating cell, identify unique molecular functions involved in nematode cell migration, and suggest similar functions in humans.

6,144 citations


"Impact of microbiota on central ner..." refers background in this paper

  • ...Aβ overload and tau aggregation foster microtubule destabilization, synaptic deficiency, disruption of Ca2 homeostasis in neurons, and ultimately neuronal apoptosis [173, 174]....

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Journal ArticleDOI
TL;DR: Astrocyte functions in healthy CNS, mechanisms and functions of reactive astrogliosis and glial scar formation, and ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions are reviewed.
Abstract: Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.

4,075 citations


"Impact of microbiota on central ner..." refers background in this paper

  • ...Astrocyte is the most abundant cell population in CNS and they outnumber neurons by almost fivefold [83]....

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