scholarly journals Gut microbiota, the pharmabiotics they produce and host health

2014 ◽  
Vol 73 (4) ◽  
pp. 477-489 ◽  
Author(s):  
Elaine Patterson ◽  
John F. Cryan ◽  
Gerald F. Fitzgerald ◽  
R. Paul Ross ◽  
Timothy G. Dinan ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Brain Function ◽  
Innate Immune ◽  
Aminobutyric Acid ◽  
Intestinal Lumen ◽  
Bioactive Metabolites ◽  
Bioactive Lipids ◽  
Disease States ◽  
Host Health ◽  
The Brain

A healthy gut microbiota plays many crucial functions in the host, being involved in the correct development and functioning of the immune system, assisting in the digestion of certain foods and in the production of health-beneficial bioactive metabolites or ‘pharmabiotics’. These include bioactive lipids (including SCFA and conjugated linoleic acid) antimicrobials and exopolysaccharides in addition to nutrients, including vitamins B and K. Alterations in the composition of the gut microbiota and reductions in microbial diversity are highlighted in many disease states, possibly rendering the host susceptible to infection and consequently negatively affecting innate immune function. Evidence is also emerging of microbially produced molecules with neuroactive functions that can have influences across the brain–gut axis. For example, γ-aminobutyric acid, serotonin, catecholamines and acetylcholine may modulate neural signalling within the enteric nervous system, when released in the intestinal lumen and consequently signal brain function and behaviour. Dietary supplementation with probiotics and prebiotics are the most widely used dietary adjuncts to modulate the gut microbiota. Furthermore, evidence is emerging of the interactions between administered microbes and dietary substrates, leading to the production of pharmabiotics, which may directly or indirectly positively influence human health.

scholarly journals Design of a Novel Synbiotic Formulation to Optimize Gut-derived Phenolic Acid Mediated Gut-brain Axis Signals for the Treatment of Stress-induced Depression and Anxiety (OR23-03-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Susan Westfall ◽  
Giulio Pasinetti
Keyword(s):  
Gut Microbiota ◽  
Therapeutic Efficacy ◽  
Toxicity Testing ◽  
Innate Immune ◽  
Bioactive Metabolites ◽  
Inflammasome Activation ◽  
Funding Sources ◽  
Psychological Impairment

Abstract Objectives Synbiotics, the combination of probiotics and prebiotics, may optimize the production of polyphenolic metabolites, and act as therapeutic agents for inflammation-induced depression. Recent evidence suggests that dysregulated immune activity increases susceptibility to depression and that bioactive polyphenolic metabolites can effectively reduce that inflammation. The problem remains that bioactive metabolite production is dependent on the gut microbiota, leading to significant interpersonal variation in the metabolites’ therapeutic efficacy. The hypothesis of the study is that the synbiotic will standardize production and bioavailability of bioactive metabolites capable of suppressing innate immune biological signatures of depression. Methods To standardize the production of bioactive metabolites, the synbiotic will be designed in an innovative in vitro model of the human gastrointestinal tract using a multivariate regression algorithm to predict which probiotic formulation produces the most effective bioactive metabolites. Following in vivo bioavailability and toxicity testing, the synbiotic's therapeutic efficacy was tested in a chronic unpredictable stress (CUS) mouse model of depression by measuring specific behaviors and changes to the gut microbiota populations. These changes were correlated to biological markers of depression modulated by the synbiotic-derived metabolites including neurobiological markers of depression and variations in innate immune markers, including interleukin-1β (IL-1β). Results In this study, we show that a synbiotic combining a dietary polyphenolic preparation with L. plantarum and B. longum can potentiate the reduction in anxiety and depression in male mice subjected to a 28 day CUS protocol, as compared to polyphenolic treatment alone. Interestingly, we found that the synbiotic may mediate microglia inflammasome activation. This finding was reflected by inhibition of NLRP3-mediated generation of IL-1β in microglia. Conclusions Collectively, these results support the potential role of a synbiotic in the potentiation of attenuation of psychological impairment in a model of depression through mechanisms that involved innate immune NLRP3 inflammation mediation in microglia. Funding Sources This project was funding a P50 CARBON Center grant from the NCCIH/ODS (Pasinetti, PD/PI).

scholarly journals Current Paradigms to Explore the Gut Microbiota Linkage to Neurological Disorders

EMJ Neurology ◽  
2020 ◽  
pp. 68-79
Author(s):  
Varruchi Sharma ◽  
Atul Sankhyan ◽  
Anshika Varshney ◽  
Renuka Choudhary ◽  
Anil K. Sharma
Keyword(s):  
Gut Microbiota ◽  
Neurological Disorders ◽  
Brain Function ◽  
Intervention Strategy ◽  
Neurological Complications ◽  
Communication Link ◽  
Brain Functions ◽  
Current Review ◽  
The Impact ◽  
The Brain

It has been suggested that an intricate communication link exists between the gut microbiota and the brain and its ability to modulate behaviour of an individual governing homeostasis. Metabolic activity of the microbiota is considered to be relatively constant in healthy individuals, despite differences in the composition of microbiota. The metabolites produced by gut microbiota and their homeostatic balance is often perturbed as a result of neurological complications. Therefore, it is of paramount importance to explore the link between gut microbiota and brain function and behaviour through neural, endocrine, and immune pathways. This current review focusses on the impact of altered gut microbiota on brain functions and how microbiome modulation by use of probiotics, prebiotics, and synbiotics might prove beneficial in the prevention and/or treatment of neurological disorders. It is important to carefully understand the complex mechanisms underlying the gut–brain axis so as to use the gut microbiota as a therapeutic intervention strategy for neurological disorders.

scholarly journals Drosophila as a Model for Microbiota Studies of Neurodegeneration

2021 ◽  
pp. 1-12
Author(s):  
Fukiko Kitani-Morii ◽  
Robert P. Friedland ◽  
Hideki Yoshida ◽  
Toshiki Mizuno
Keyword(s):  
Gut Microbiota ◽  
Molecular Mechanisms ◽  
Environmental Changes ◽  
Fruit Fly ◽  
Endocrine Regulation ◽  
Nutrient Metabolism ◽  
Host Health ◽  
And Behavior ◽  
The Brain ◽  
Lateral Sclerosis

Accumulating evidence show that the gut microbiota is deeply involved not only in host nutrient metabolism but also in immune function, endocrine regulation, and chronic disease. In neurodegenerative conditions such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis, the gut-brain axis, the bidirectional interaction between the brain and the gut, provides new route of pathological spread and potential therapeutic targets. Although studies of gut microbiota have been conducted mainly in mice, mammalian gut microbiota is highly diverse, complex, and sensitive to environmental changes. Drosophila melanogaster, a fruit fly, has many advantages as a laboratory animal: short life cycle, numerous and genetically homogenous offspring, less ethical concerns, availability of many genetic models, and low maintenance costs. Drosophila has a simpler gut microbiota than mammals and can be made to remain sterile or to have standardized gut microbiota by simple established methods. Research on the microbiota of Drosophila has revealed new molecules that regulate the brain-gut axis, and it has been shown that dysbiosis of the fly microbiota worsens lifespan, motor function, and neurodegeneration in AD and PD models. The results shown in fly studies represents a fundamental part of the immune and proteomic process involving gut-microbiota interactions that are highly conserved. Even though the fly’s gut microbiota are not simple mimics of humans, flies are a valuable system to learn the molecular mechanisms of how the gut microbiota affect host health and behavior.

scholarly journals A half century of γ-aminobutyric acid

2019 ◽  
Vol 3 ◽  
pp. 239821281985824 ◽  
Author(s):  
Trevor G Smart ◽  
F Anne Stephenson
Keyword(s):  
Nervous System ◽  
Molecular Cloning ◽  
Brain Function ◽  
Drug Targets ◽  
Neurological Diseases ◽  
Aminobutyric Acid ◽  
Receptor Subtypes ◽  
Acid Receptor ◽  
Neural Excitability ◽  
The Brain

γ-aminobutyric acid has become one of the most widely known neurotransmitter molecules in the brain over the last 50 years, recognised for its pivotal role in inhibiting neural excitability. It emerged from studies of crustacean muscle and neurons before its significance to the mammalian nervous system was appreciated. Now, after five decades of investigation, we know that most neurons are γ-aminobutyric-acid-sensitive, it is a cornerstone of neural physiology and dysfunction to γ-aminobutyric acid signalling is increasingly documented in a range of neurological diseases. In this review, we briefly chart the neurodevelopment of γ-aminobutyric acid and its two major receptor subtypes: the γ-aminobutyric acidA and γ-aminobutyric acidB receptors, starting from the humble invertebrate origins of being an ‘interesting molecule’ acting at a single γ-aminobutyric acid receptor type, to one of the brain’s most important neurochemical components and vital drug targets for major therapeutic classes of drugs. We document the period of molecular cloning and the explosive influence this had on the field of neuroscience and pharmacology up to the present day and the production of atomic γ-aminobutyric acidA and γ-aminobutyric acidB receptor structures. γ-Aminobutyric acid is no longer a humble molecule but the instigator of rich and powerful signalling processes that are absolutely vital for healthy brain function.

scholarly journals Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Yan Wang ◽  
Qian Tong ◽  
Shu-Rong Ma ◽  
Zhen-Xiong Zhao ◽  
Li-Bin Pan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Brain Function ◽  
Intestinal Bacteria ◽  
Brain Dopamine ◽  
Laser Desorption Mass Spectrometry ◽  
Ms Imaging ◽  
Rate Limiting ◽  
The Brain

AbstractThe phenylalanine–tyrosine–dopa–dopamine pathway provides dopamine to the brain. In this process, tyrosine hydroxylase (TH) is the rate-limiting enzyme that hydroxylates tyrosine and generates levodopa (l-dopa) with tetrahydrobiopterin (BH4) as a coenzyme. Here, we show that oral berberine (BBR) might supply H• through dihydroberberine (reduced BBR produced by bacterial nitroreductase) and promote the production of BH4 from dihydrobiopterin; the increased BH4 enhances TH activity, which accelerates the production of l-dopa by the gut bacteria. Oral BBR acts in a way similar to vitamins. The l-dopa produced by the intestinal bacteria enters the brain through the circulation and is transformed to dopamine. To verify the gut–brain dialog activated by BBR’s effect, Enterococcus faecalis or Enterococcus faecium was transplanted into Parkinson’s disease (PD) mice. The bacteria significantly increased brain dopamine and ameliorated PD manifestation in mice; additionally, combination of BBR with bacteria showed better therapeutic effect than that with bacteria alone. Moreover, 2,4,6-trimethyl-pyranylium tetrafluoroborate (TMP-TFB)-derivatized matrix-assisted laser desorption mass spectrometry (MALDI-MS) imaging of dopamine identified elevated striatal dopamine levels in mouse brains with oral Enterococcus, and BBR strengthened the imaging intensity of brain dopamine. These results demonstrated that BBR was an agonist of TH in Enterococcus and could lead to the production of l-dopa in the gut. Furthermore, a study of 28 patients with hyperlipidemia confirmed that oral BBR increased blood/fecal l-dopa by the intestinal bacteria. Hence, BBR might improve the brain function by upregulating the biosynthesis of l-dopa in the gut microbiota through a vitamin-like effect.

Effect of Ethanol on Entry of some Substances into the Brains of Rats

1971 ◽  
Vol 49 (9) ◽  
pp. 833-840 ◽  
Author(s):  
Crystal A. Leslie ◽  
Zehava Gottesfeld ◽  
K. A. C. Elliott
Keyword(s):  
Urinary Excretion ◽  
Brain Function ◽  
Red Cells ◽  
Aminobutyric Acid ◽  
Ethanol Administration ◽  
Gaba Concentration ◽  
Endogenous Gaba ◽  
The Brain ◽  
Uptake And Metabolism

We have examined the effects of a subanesthetic dose of ethanol on the entry into the brains of rats of three 14C-labelled substances which are known to affect brain function. All substances were given intraperitoneally. When ethanol was given the concentration of pentobarbital in the brain reached and was maintained at a higher level than without ethanol. The barbiturate entered the brain and became distributed between plasma, red cells, and brain extremely rapidly in the presence or absence of ethanol. Administration of ethanol decreased the rate of breakdown of pentobarbital, so that higher levels of unchanged pentobarbital were maintained in blood, liver, and brain. Breakdown of the barbiturate occurred rapidly in liver but almost no radioactive breakdown products entered or were formed in the brain. Thiamine entered the brain sparingly but, after 60 min, the ratio of radioactivity per gram of brain to that per milliliter of plasma became considerably greater with ethanol than without. In the absence or presence of ethanol this ratio increased with time due to a rapid disappearance of radioactivity from the plasma while radioactivity in the brain tended to increase slightly. In the presence of ethanol the rate of disappearance from the plasma increased, presumably due to increased uptake and metabolism of thiamine by other tissues. Urinary excretion of radioactivity decreased. Injected γ-aminobutyric acid (GABA), entered the brain very sparingly and much of what entered was metabolized. Ethanol had no effect on the endogenous GABA concentration in the brain nor on the entry or metabolism of injected GABA.

scholarly journals Rapid Control of Brain Aromatase Activity by Glutamatergic Inputs

Endocrinology ◽  
2006 ◽  
Vol 147 (1) ◽  
pp. 359-366 ◽  
Author(s):  
Jacques Balthazart ◽  
Michelle Baillien ◽  
Gregory F. Ball
Keyword(s):  
Brain Function ◽  
Time Course ◽  
Aminobutyric Acid ◽  
Aromatase Activity ◽  
Brain Aromatase ◽  
Rapid Control ◽  
Rapid Changes ◽  
Glutamate Agonists ◽  
Membrane Effects ◽  
The Brain

Estrogens derived from the neural aromatization of testosterone play a key role in the activation of male sexual behavior in many vertebrates and have now been recognized to have rapid membrane effects on brain function. Such changes in aromatase activity and hence in local estrogen concentrations could rapidly modulate behavioral responses. We show here that there is a very rapid (within minutes) decrease in aromatase activity in quail hypothalamic explants exposed to treatments affecting intracellular Ca2+ concentrations, such as the addition of glutamate agonists (kainate, α-amino-3-hydroxymethyl-4-isoxazole propionic acid, and, to a much lesser extent, N-methyl-d-aspartate), but not of γ-aminobutyric acid. The kainate effects, which reduce aromatase activity by 25–50%, are observed within 5 min, are completely blocked in explants exposed to specific kainate antagonists (6-cyano-7-nitroquinoxaline-2,3-dione disodium or 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium), and are also rapidly reversible when effectors are washed out. Together, these data support the idea that the synthesis of estrogen can be rapidly regulated in the brain, thus producing rapid changes in local estrogen bioavailability that could rapidly modify brain function with a time course similar to what has previously been described for neurotransmitters and neuromodulators.

Immunological Responses to Gut Bacteria

2012 ◽  
Vol 95 (1) ◽  
pp. 35-49 ◽  
Author(s):  
Julia M Green-Johnson
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Host Defenses ◽  
Immunological Responses ◽  
Host Health ◽  
Microbe Interactions ◽  
Host Microbe Interactions

Abstract The integral nature of interactions between the gut microbiota and host is especially evident with respect to effects on the immune system and host defenses. Host-microbiota interactions are increasingly being revealed as complex and dynamic, with far-reaching effects on varied aspects of host health. This review focuses on adaptive and innate immune responses to the gut microbiota and the bidirectional nature of these host-microbe interactions.

scholarly journals Review: Effect of Gut Microbiota and Its Metabolite SCFAs on Radiation-Induced Intestinal Injury

2021 ◽  
Vol 11 ◽  
Author(s):  
Yangyang Li ◽  
Yiming Zhang ◽  
Kongxi Wei ◽  
Jinpeng He ◽  
Nan Ding ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Second Messengers ◽  
Short Chain Fatty Acids ◽  
Intestinal Injury ◽  
Beneficial Bacteria ◽  
Specific Mechanism ◽  
Disease States ◽  
Host Health ◽  
Radiation Induced ◽  
Abundance And Diversity

Gut microbiota is regarded as the second human genome and forgotten organ, which is symbiotic with the human host and cannot live and exist alone. The gut microbiota performs multiple physiological functions and plays a pivotal role in host health and intestinal homeostasis. However, the gut microbiota can always be affected by various factors and among them, it is radiotherapy that results in gut microbiota 12dysbiosis and it is often embodied in a decrease in the abundance and diversity of gut microbiota, an increase in harmful bacteria and a decrease in beneficial bacteria, thereby affecting many disease states, especially intestine diseases. Furthermore, gut microbiota can produce a variety of metabolites, among which short-chain fatty acids (SCFAs) are one of the most abundant and important metabolites. More importantly, SCFAs can be identified as second messengers to promote signal transduction and affect the occurrence and development of diseases. Radiotherapy can lead to the alterations of SCFAs-producing bacteria and cause changes in SCFAs, which is associated with a variety of diseases such as radiation-induced intestinal injury. However, the specific mechanism of its occurrence is not yet clear. Therefore, this review intends to emphasize the alterations of gut microbiota after radiotherapy and highlight the alterations of SCFAs-producing bacteria and SCFAs to explore the mechanisms of radiation-induced intestinal injury from the perspective of gut microbiota and its metabolite SCFAs.

scholarly journals Impact of Gut Microbiome Lactobacillus spp. in Brain Function and its Medicament towards Alzheimer’s Disease Pathogenesis

2021 ◽  
Author(s):  
Shani Kunjamma John ◽  
Vani Chandrapragasam ◽  
Pinaki Dey
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gut Microbiota ◽  
Brain Function ◽  
Neurodegenerative Dementia ◽  
Type Ii Diabetics ◽  
Health Complications ◽  
Effects Of Aging ◽  
The Brain ◽  
Significant Health

Alzheimer’s disease is neurodegenerative dementia which has significant health complications in the old age group. An imbalance in gut microbiota can influence to cause several diseases like chronic disorders, depression, type II diabetics, and neurological disorders like AD. Aging is one of the major causes of the development of neurodegenerative disease due to the decreasing levels of neurotransmitters, oxidative stress, chronic inflammation, and apoptosis. These harmful effects of aging can be prevented by probiotics usage. The gut-microbiota is capable to control the brain function through the gut-brain axis. Lactobacillus strains are considered as beneficial microorganism because of its importance of the maintenance in healthy intestinal microflora, immunomodulation, and intestinal pathogenic intervention. They have diverse applications in the medical field with properties like antioxidant, anticancer, anti-inflammatory, anti-proliferative, anti-obesity, and anti-diabetic activities. Probiotic supplementation with Lactobacillus strains shows an optimistic trend to use it as a significant therapy for cognitive symptoms. This review article put forwards the significance of the gut-brain axis and the contribution of Lactobacillus strains as a probiotic supplement and its therapeutic innovations for future aspects and the limitation to treat AD-related pathogenesis are briefly elucidated.

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