Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly
TL;DR: The data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella, and a reduction in the abundances of an anti-inflammatoryTaxon, E. rectale, are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis.
About: This article is published in Neurobiology of Aging.The article was published on 2017-01-01 and is currently open access. It has received 761 citations till now. The article focuses on the topics: Inflammasome complex & Amyloidosis.
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TL;DR: Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.
Abstract: The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within ...
1,775 citations
10 Jan 2019
TL;DR: This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases.
Abstract: Each individual is provided with a unique gut microbiota profile that plays many specific functions in host nutrient metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Gut microbiota are composed of different bacteria species taxonomically classified by genus, family, order, and phyla. Each human’s gut microbiota are shaped in early life as their composition depends on infant transitions (birth gestational date, type of delivery, methods of milk feeding, weaning period) and external factors such as antibiotic use. These personal and healthy core native microbiota remain relatively stable in adulthood but differ between individuals due to enterotypes, body mass index (BMI) level, exercise frequency, lifestyle, and cultural and dietary habits. Accordingly, there is not a unique optimal gut microbiota composition since it is different for each individual. However, a healthy host–microorganism balance must be respected in order to optimally perform metabolic and immune functions and prevent disease development. This review will provide an overview of the studies that focus on gut microbiota balances in the same individual and between individuals and highlight the close mutualistic relationship between gut microbiota variations and diseases. Indeed, dysbiosis of gut microbiota is associated not only with intestinal disorders but also with numerous extra-intestinal diseases such as metabolic and neurological disorders. Understanding the cause or consequence of these gut microbiota balances in health and disease and how to maintain or restore a healthy gut microbiota composition should be useful in developing promising therapeutic interventions.
1,502 citations
Cites background from "Association of brain amyloidosis wi..."
...[97] demonstrated that an increase in Escherichia/Shigella abundance and a reduction of E....
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TL;DR: The gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals, which adds AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.
Abstract: Alzheimer’s disease (AD) is the most common form of dementia. However, the etiopathogenesis of this devastating disease is not fully understood. Recent studies in rodents suggest that alterations in the gut microbiome may contribute to amyloid deposition, yet the microbial communities associated with AD have not been characterized in humans. Towards this end, we characterized the bacterial taxonomic composition of fecal samples from participants with and without a diagnosis of dementia due to AD. Our analyses revealed that the gut microbiome of AD participants has decreased microbial diversity and is compositionally distinct from control age- and sex-matched individuals. We identified phylum- through genus-wide differences in bacterial abundance including decreased Firmicutes, increased Bacteroidetes, and decreased Bifidobacterium in the microbiome of AD participants. Furthermore, we observed correlations between levels of differentially abundant genera and cerebrospinal fluid (CSF) biomarkers of AD. These findings add AD to the growing list of diseases associated with gut microbial alterations, as well as suggest that gut bacterial communities may be a target for therapeutic intervention.
1,115 citations
TL;DR: In this article, the authors investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus.
Abstract: Objective Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the GI tract is involved in this disease. We investigated whether the gut microbiome is linked to disease severity in patients with COVID-19, and whether perturbations in microbiome composition, if any, resolve with clearance of the SARS-CoV-2 virus. Methods In this two-hospital cohort study, we obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Serial stool samples were collected from 27 of the 100 patients up to 30 days after clearance of SARS-CoV-2. Gut microbiome compositions were characterised by shotgun sequencing total DNA extracted from stools. Concentrations of inflammatory cytokines and blood markers were measured from plasma. Results Gut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals irrespective of whether patients had received medication (p Conclusion Associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-19 suggest that the gut microbiome is involved in the magnitude of COVID-19 severity possibly via modulating host immune responses. Furthermore, the gut microbiota dysbiosis after disease resolution could contribute to persistent symptoms, highlighting a need to understand how gut microorganisms are involved in inflammation and COVID-19.
686 citations
TL;DR: Emerging and exciting evidence of intricate and crucial connections between the gut microbiota and the brain involving multiple biological systems, and possible contributions by the Gut microbiota to neurological disorders are discussed.
Abstract: In a striking display of trans-kingdom symbiosis, gut bacteria cooperate with their animal hosts to regulate the development and function of the immune, metabolic and nervous systems through dynamic bidirectional communication along the ‘gut–brain axis’. These processes may affect human health, as certain animal behaviours appear to correlate with the composition of gut bacteria, and disruptions in microbial communities have been implicated in several neurological disorders. Most insights about host–microbiota interactions come from animal models, which represent crucial tools for studying the various pathways linking the gut and the brain. However, there are complexities and manifest limitations inherent in translating complex human disease to reductionist animal models. In this Review, we discuss emerging and exciting evidence of intricate and crucial connections between the gut microbiota and the brain involving multiple biological systems, and possible contributions by the gut microbiota to neurological disorders. Continued advances from this frontier of biomedicine may lead to tangible impacts on human health. In this Review, Morais, Schreiber and Mazmanian discuss emerging and exciting evidence of intricate and potentially important connections between the gut microbiota and the brain involving multiple biological systems, and possible contributions by the gut microbiota to complex behaviours.
615 citations
References
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TL;DR: A simplified, scored form of the cognitive mental status examination, the “Mini-Mental State” (MMS) which includes eleven questions, requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
76,181 citations
"Association of brain amyloidosis wi..." refers methods in this paper
...Assessment included evaluation of: - global cognition (Mini-Mental State Examination MMSE, and Alzheimer’s Disease Assessment Scale – Cognitive ADAS-COG); - long-term memory (Story Recall Test, Rey Auditory-Verbal Learning Test – immediate and delayed recall (Rey AVLT), and Recall of Rey-Osterrieth Complex Figure); - attention (Trail Making Test – Part A TMT-A); M AN US CR IP T AC CE PT ED 21 - language (Token Test, Action and Object naming -subtest from the Battery for Analysis of Aphasic Deficits, BADA-, and Letter and Category Fluency); - constructional and visuo-spatial abilities (Copy of Rey-Osterrieth Complex Figure); - upper limb apraxia (Movement imitation Test); - executive functions (Trail Making Test – Part B (TMT-B), and Wisconsin Card Sorting Test (WCST)); - non-verbal reasoning (Raven’s Coloured Progressive Matrices (Raven’s CPM))....
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...…and functional history, physical examination including collection of height and weight, neurological examination, drug history, mood an M AN US CR IP T AC CE PT ED 8 behaviour assessment, and neuropsychological assessment including the Mini Mental State Exam (MMSE) (Folstein et al., 1975)....
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...We assessed possible associations between the demographic variables age, gender and BMI, with the levels of the cytokines and we found a significant correlation between NLRP3 and age (r=0.27, p=0.013), between IL-6 and age (r=-0.24, p=0.032) and between IL-18 and gender (r=0.25, p=0.022) Thus, in addition to MMSE, we have also included age and/or gender as covariates, whenever c ssary, in the analyses....
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...Thus, BMI was included, together with the MMSE, as a covariate in the GLM with Pseudomonas aeruginosa as dependent variable....
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...In particular, Amy+ showed lower abundance of Eubacterium rectale and higher abundance of Escherichia/Shigella as compared to both HC (FC=-9.6, p<0.001 and FC=+12.8, p<0.001; MMSE p= 0.029 and 0.104 respectively) and to Amy- (FC=-7.7, p<0.001 and FC=+7.4, p=0.003; MMSE p= 0.053 and 0.205 respectively)....
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01 Jan 2002
TL;DR: The Mini-Mental State (MMS) as mentioned in this paper is a simplified version of the standard WAIS with eleven questions and requires only 5-10 min to administer, and is therefore practical to use serially and routinely.
Abstract: EXAMINATION of the mental state is essential in evaluating psychiatric patients.1 Many investigators have added quantitative assessment of cognitive performance to the standard examination, and have documented reliability and validity of the several “clinical tests of the sensorium”.2*3 The available batteries are lengthy. For example, WITHERS and HINTON’S test includes 33 questions and requires about 30 min to administer and score. The standard WAIS requires even more time. However, elderly patients, particularly those with delirium or dementia syndromes, cooperate well only for short periods.4 Therefore, we devised a simplified, scored form of the cognitive mental status examination, the “Mini-Mental State” (MMS) which includes eleven questions, requires only 5-10 min to administer, and is therefore practical to use serially and routinely. It is “mini” because it concentrates only on the cognitive aspects of mental functions, and excludes questions concerning mood, abnormal mental experiences and the form of thinking. But within the cognitive realm it is thorough. We have documented the validity and reliability of the MMS when given to 206 patients with dementia syndromes, affective disorder, affective disorder with cognitive impairment “pseudodementia”5T6), mania, schizophrenia, personality disorders, and in 63 normal subjects.
70,887 citations
TL;DR: This protocol provides an overview of the comparative CT method for quantitative gene expression studies and various examples to present quantitative gene Expression data using this method.
Abstract: Two different methods of presenting quantitative gene expression exist: absolute and relative quantification. Absolute quantification calculates the copy number of the gene usually by relating the PCR signal to a standard curve. Relative gene expression presents the data of the gene of interest relative to some calibrator or internal control gene. A widely used method to present relative gene expression is the comparative C(T) method also referred to as the 2 (-DeltaDeltaC(T)) method. This protocol provides an overview of the comparative C(T) method for quantitative gene expression studies. Also presented here are various examples to present quantitative gene expression data using this method.
20,580 citations
University Hospital Bonn1, University of California, Riverside2, Harvard University3, Case Western Reserve University4, University of Illinois at Chicago5, European Institute6, VA Palo Alto Healthcare System7, Stanford University8, Spanish National Research Council9, Cleveland Clinic Lerner Research Institute10, Hong Kong University of Science and Technology11, University of California, Los Angeles12, University of Southern Denmark13, University of Cambridge14, University of Manchester15, University of the Basque Country16, Ikerbasque17, RIKEN Brain Science Institute18, University of Eastern Finland19, University of Bonn20, University of Massachusetts Medical School21, Center of Advanced European Studies and Research22, University of Southern California23, University of South Florida24, Duke University25, Southampton General Hospital26, University of Southampton27, Moorgreen Hospital28, Louisiana State University29, Imperial College London30, Centre national de la recherche scientifique31, Karolinska Institutet32, Max Planck Society33, University of Tübingen34, University of Groningen35, University of Colorado Denver36, Douglas Mental Health University Institute37
TL;DR: Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction.
Abstract: Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.
3,947 citations
"Association of brain amyloidosis wi..." refers background in this paper
...…mediated by activated microglia, reactive astrocytes and complement activation, that have been especially observed in the vicinity of amyloid plaques and even in the early stages of AD (Heppner et al., 2015; Clark et al., 2015; Heneka et al., 2015; Latta et al., 2015; Stoeck et al., 2014)....
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TL;DR: The emerging concept of a microbiota–gut–brain axis suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders.
Abstract: Recent years have witnessed the rise of the gut microbiota as a major topic of research interest in biology. Studies are revealing how variations and changes in the composition of the gut microbiota influence normal physiology and contribute to diseases ranging from inflammation to obesity. Accumulating data now indicate that the gut microbiota also communicates with the CNS — possibly through neural, endocrine and immune pathways — and thereby influences brain function and behaviour. Studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic bacteria or antibiotic drugs suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain. Thus, the emerging concept of a microbiota-gut-brain axis suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders.
3,058 citations