Bidirectional Axis Research Articles

The role of gut-islet axis in pancreatic islet function and glucose homeostasis.

The gastrointestinal tract plays a vital role in the occurrence and treatment of metabolic diseases. Recent studies have convincingly demonstrated a bidirectional axis of communication between the gut and islets, enabling the gut to influence glucose metabolism and energy homeostasis in animals strongly. The 'gut-islet axis' is an essential endocrine signal axis that regulates islet function through the dialogue between intestinal microecology and endocrine metabolism. The discovery of glucagon-like peptide-1 (GLP-1), gastric inhibitory peptide (GIP) and other gut hormones has initially set up a bridge between gut and islet cells. However, the influence of other factors remains largely unknown, such as the homeostasis of the gut microbiota and the integrity of the gut barrier. Although gut microbiota primarily resides and affect intestinal function, they also affect extra-intestinal organs by absorbing and transferring metabolites derived from microorganisms. As a result of this transfer, islets may be continuously exposed to gut-derived metabolites and components. Changes in the composition of gut microbiota can damage the intestinal barrier function to varying degrees, resulting in increased intestinal permeability to bacteria and their derivatives. All these changes contribute to the severe disturbance of critical metabolic pathways in peripheral tissues and organs. In this review, we have outlined the different gut-islet axis signalling mechanisms associated with metabolism and summarized the latest progress in the complex signalling molecules of the gut and gut microbiota. In addition, we will discuss the impact of the gut renin-angiotensin system (RAS) on the various components of the gut-islet axis that regulate energy and glucose homeostasis. This work also indicates that therapeutic approaches aiming to restore gut microbial homeostasis, such as probiotics and faecal microbiota transplantation (FMT), have shown great potential in improving treatment outcomes, enhancing patient prognosis and slowing down disease progression. Future research should further uncover the molecular links between the gut-islet axis and the gut microbiota and explore individualized microbial treatment strategies, which will provide an innovative perspective and approach for the diagnosis and treatment of metabolic diseases.

The Role of Ion-Transporting Proteins on Crosstalk Between the Skeletal Muscle and Central Nervous Systems Elicited by Physical Exercise.

A paradigm shift in the understanding of bidirectional interactions between peripheral and central nervous systems is essential for development of rehabilitation and preventive interventions based on physical exercise. Although a causal relationship has not been completely established, modulation of voltage-dependent ion channels (Ca2+, Cl-, K+, Na+, lactate-, H+) in skeletal and neuronal cells provides opportunities to maintain force production during exercise and reduce the risk of disease. However, there are caveats to consider when interpreting the effects of physical exercise on this bidirectional axis, since exercise protocol details (e.g., duration and intensity) have variable effects on this crosstalk. Therefore, an integrative perspective of the skeletal muscle and brain's communication pathway is discussed, and the role of physical exercise on such communication highway is explained in this review.

Importance of good hosting: reviewing the bi-directionality of the microbiome-gut-brain-axis.

Gut microorganisms have been shown to significantly impact on central function and studies that have associated brain disorders with specific bacterial genera have advocated an anomalous gut microbiome as the pathophysiological basis of several psychiatric and neurological conditions. Thus, our knowledge of brain-to-gut-to microbiome communication in this bidirectional axis seems to have been overlooked. This review examines the known mechanisms of the microbiome-to-gut-to-brain axis, highlighting how brain-to-gut-to-microbiome signaling may be key to understanding the cause of disrupted gut microbial communities. We show that brain disorders can alter the function of the brain-to-gut-to-microbiome axis, which will in turn contribute to disease progression, while the microbiome-to gut-to brain direction presents as a more versatile therapeutic axis, since current psychotropic/neurosurgical interventions may have unwanted side effects that further cause disruption to the gut microbiome. A consideration of the brain-to-gut-to-microbiome axis is imperative to better understand how the microbiome-gut-brain axis overall is involved in brain illnesses, and how it may be utilized as a preventive and therapeutic tool.

CircHAS2 activates CCNE2 to promote cell proliferation and sensitizes the response of colorectal cancer to anlotinib

BackgroundTyrosine kinase inhibitors (TKIs) are crucial in the targeted treatment of advanced colorectal cancer (CRC). Anlotinib, a multi-target TKI, has previously been demonstrated to offer therapeutic benefits in previous studies. Circular RNAs (circRNAs) have been implicated in CRC progression and their unique structural stability serves as promising biomarkers. The detailed molecular mechanisms and specific biomarkers related to circRNAs in the era of targeted therapies, however, remain obscure.MethodsThe whole transcriptome RNA sequencing and function experiments were conducted to identify candidate anlotinib-regulated circRNAs, whose mechanism was confirmed by molecular biology experiments. CircHAS2 was profiled in a library of patient-derived CRC organoids (n = 22) and patient-derived CRC tumors in mice. Furthermore, a prospective phase II clinical study of 14 advanced CRC patients with anlotinib-based therapy was commenced to verify drug sensitivity (ClinicalTrials.gov identifier: NCT05262335).ResultsAnlotinib inhibits tumor growth in vitro and in vivo by downregulating circHAS2. CircHAS2 modulates CCNE2 activation by acting as a sponge for miR-1244, and binding to USP10 to facilitate p53 nuclear export as well as degradation. In parallel, circHAS2 serves as a potent biomarker predictive of anlotinib sensitivity, both in patient-derived organoids and xenograft models. Moreover, the efficacy of anlotinib inclusion into the treatment regimen yields meaningful clinical responses in patients with high levels of circHAS2. Our findings offer a promising targeted strategy for approximately 52.9% of advanced CRC patients who have high circHAS2 levels.ConclusionsCircHAS2 promotes cell proliferation via the miR-1244/CCNE2 and USP10/p53/CCNE2 bidirectional axes. Patient-derived organoids and xenograft models are employed to validate the sensitivity to anlotinib. Furthermore, our preliminary Phase II clinical study, involving advanced CRC patients treated with anlotinib, confirmed circHAS2 as a potential sensitivity marker.

Thymic Innervation Impairment in Experimental Autoimmune Encephalomyelitis

Introduction: The thymus is the primary lymphoid organ responsible for normal T-cell development. Yet, in abnormal metabolic conditions as well as an acute infection, the organ exhibits morphological and cellular alterations. It is well established that the immune system is in a tidy connection and dependent on the central nervous system (CNS), which regulates thymic function by means of innervation and neurotransmitters. Sympathetic innervation leaves the CNS and spreads through thymic tissue, where nerve endings interact directly or indirectly with thymic cells contributing to their maintenance and development. Methods: Herein, we hypothesized that brain damage due to an inflammatory process might elicit alterations upon the thymic-CNS neuroimmune axis, altering not just the sympathetic innervation and neurotransmitter release, but also modifying the thymus microenvironment and T-cell development. We used the well-established multiple sclerosis model of experimental autoimmune encephalomyelitis (EAE), to study putative changes in the thymic neural, lymphoid, and microenvironmental compartments. Results: We showed that along with EAE clinical development, thymus morphology, and cellular compartments are affected, altering the peripheric T-cell population and modifying the retrograde thymic communication toward the CNS. Conclusion: Altogether, our data suggest that the thymic-CNS neuroimmune bidirectional axis is compromised in EAE. This imbalance may contribute to an increased and uncontrolled auto-immune reaction.

Ambient particulate matter (PM2.5) exposure contributes to neurodegeneration through the microbiome-gut-brain axis: Therapeutic role of melatonin

Exposure to ambient particulate matter (PM2.5) has been shown to disturb the gut microbiome homeostasis and cause initiation of neuroinflammation and neurodegeneration via gut-brain bi-directional axis. Polyaromatic hydrocarbons (PAHs), which are carcinogenic and mutagenic, are important organic constituents of PM2.5 that could be involved in the microbiome-gut-brain axis-mediated neurodegeneration. Melatonin (ML) has been shown to modulate the microbiome and curb inflammation in the gut and brain. However, no studies have been reported for its effect on PM2.5-induced neuroinflammation. In the current study, it was observed that treatment with ML at 100 µM significantly inhibits microglial activation (HMC-3 cells) and colonic inflammation (CCD-841 cells) by the conditioned media from PM2.5 exposed BEAS2B cells. Further, melatonin treatment at a dose of 50 mg/kg to C57BL/6 mice exposed to PM2.5 (at a dose of 60 µg/animal) for 90 days significantly alleviated the neuroinflammation and neurodegeneration caused by PAHs in PM2.5 by modulating olfactory-brain and microbiome-gut-brain axis.

MP03-11 THE BRAIN, GUT & BLADDER HEALTH NEXUS UNDERLYING STRESS & MENTAL HEALTH DISORDERS IN WOMEN

You have accessJournal of UrologyCME1 Apr 2023MP03-11 THE BRAIN, GUT & BLADDER HEALTH NEXUS UNDERLYING STRESS & MENTAL HEALTH DISORDERS IN WOMEN Ariana Smith, Amanda Berry, Linda Brubaker, Shayna Cunningham, Sheila Gahagan, Lisa Kane Low, Margaret Mueller, Siobhan Sutcliffe, Beverly Williams, and Brady Sonya Ariana SmithAriana Smith More articles by this author , Amanda BerryAmanda Berry More articles by this author , Linda BrubakerLinda Brubaker More articles by this author , Shayna CunninghamShayna Cunningham More articles by this author , Sheila GahaganSheila Gahagan More articles by this author , Lisa Kane LowLisa Kane Low More articles by this author , Margaret MuellerMargaret Mueller More articles by this author , Siobhan SutcliffeSiobhan Sutcliffe More articles by this author , Beverly WilliamsBeverly Williams More articles by this author , and Brady SonyaBrady Sonya More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003214.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The relationship between the brain, gut and bladder is complex. To aid further studies to understand the relationship between specific stressors and mental health disorders (MHD), intestinal sequelae and lower urinary tract symptoms (LUTS) we aim to identify potential mechanisms and biological processes that explain brain-gut-bladder associations in women. METHODS: Identification of mechanisms followed guidelines of conceptual model development. RESULTS: Traumatic events, chronic stressors and MHD may lead to a maladaptive stress response with implications for communication and signaling between the brain, gut and bladder. Figure 1 depicts three bidirectional axes; the gut, brain and bladder are key actors engaged in “communication” across the life course. Each organ function is guided by key inputs that ideally assist in maintaining health but also can initiate or exacerbate dysfunction. The gut can communicate with the brain and bladder in ways that shape trajectories of MHD, neuropsychological resilience, central physiological dysregulation and the likelihood of developing and experiencing persistent LUTS. Psychological stressors influence communication between the gut and the brain with accompanying alterations in gut metabolites, neurotransmitters and microbiota. Gut bacteria produce molecules and metabolites that alter production of neurotransmitters (serotonin, dopamine), amino acids (tryptophan), short chain fatty acids (butyrate, acetate) and amyloid proteins that influence the brain (neuronal, blood, immune pathways), thus mediating communication between the gut and brain. Gut bacteria also alter inflammatory immune response via endotoxins, conferring vulnerability or resistance to bladder infections. Microbiota signal neurogenesis, microglia maturation and synaptic pruning; they also calibrate brain-gut-bladder axis communication through neurotransmission, synaptogenesis & the vagus nerve. CONCLUSIONS: Some neurotransmitter alterations seen with stress may not be caused directly by perceptions of stress, but rather by stress-related alteration in intestinal bacteria. The brain-gut-bladder axis has implications for research as well as novel prevention and treatment approaches. An intriguing area for research is how the microbiome may influence the brain & bladder. Source of Funding: The Prevention of Lower Urinary Tract Symptoms (PLUS) Research Consortium is supported by the National Institutes of Health (NIH) through cooperative agreements (grants U24DK106786, U01DK106853, U01DK106858, U01DK106898, U01DK106893, U01DK106827, U01DK106908, U01DK106892, U01DK126045) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e26 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ariana Smith More articles by this author Amanda Berry More articles by this author Linda Brubaker More articles by this author Shayna Cunningham More articles by this author Sheila Gahagan More articles by this author Lisa Kane Low More articles by this author Margaret Mueller More articles by this author Siobhan Sutcliffe More articles by this author Beverly Williams More articles by this author Brady Sonya More articles by this author Expand All Advertisement PDF downloadLoading ...

Spinal Cord-Gut-Immune Axis and Its Implications Regarding Therapeutic Development for Spinal Cord Injury.

Spinal cord injury (SCI) affects ∼1,300,000 people living in the United States. Most research efforts have been focused on reversing paralysis, as this is arguably the most defining feature of SCI. The damage caused by SCI, however, extends past paralysis and includes other debilitating outcomes including immune dysfunction and gut dysbiosis. Recent efforts are now investigating the pathophysiology of and developing therapies for these more distal manifestations of SCI. One exciting avenue is the spinal cord-gut-immune axis, which proposes that gut dysbiosis amplifies lesion inflammation and impairs SCI recovery. This review will highlight the most recent findings regarding gut and immune dysfunction following SCI, and discuss how the central nervous system (CNS), gut, and immune system all coalesce to form a bidirectional axis that can impact SCI recovery. Finally, important considerations regarding how the spinal cord-gut-immune axis fits within the larger framework of therapeutic development (i.e., probiotics, fecal transplants, dietary modifications) will be discussed, emphasizing the lack of interdepartmental investigation and the missed opportunity to maximize therapeutic benefit in SCI.

Selenium in Bodily Homeostasis: Hypothalamus, Hormones, and Highways of Communication.

The ability of the body to maintain homeostasis requires constant communication between the brain and peripheral tissues. Different organs produce signals, often in the form of hormones, which are detected by the hypothalamus. In response, the hypothalamus alters its regulation of bodily processes, which is achieved through its own pathways of hormonal communication. The generation and transmission of the molecules involved in these bi-directional axes can be affected by redox balance. The essential trace element selenium is known to influence numerous physiological processes, including energy homeostasis, through its various redox functions. Selenium must be obtained through the diet and is used to synthesize selenoproteins, a family of proteins with mainly antioxidant functions. Alterations in selenium status have been correlated with homeostatic disturbances in humans and studies with animal models of selenoprotein dysfunction indicate a strong influence on energy balance. The relationship between selenium and energy metabolism is complicated, however, as selenium has been shown to participate in multiple levels of homeostatic communication. This review discusses the role of selenium in the various pathways of communication between the body and the brain that are essential for maintaining homeostasis.

Differences in gut microbiota correlate with symptoms and regional brain volumes in patients with late-life depression.

Depression is associated with gut dysbiosis that disrupts a gut-brain bidirectional axis. Gray matter volume changes in cortical and subcortical structures, including prefrontal regions and the hippocampus, have also been noted in depressive disorders. However, the link between gut microbiota and brain structures in depressed patients remains elusive. Neuropsychiatric measures, stool samples, and structural brain images were collected from 36 patients with late-life depression (LLD) and 17 healthy controls. 16S ribosomal RNA (rRNA) gene sequencing was used to profile stool microbial communities for quantitation of microbial composition, abundance, and diversity. T1-weighted brain images were assessed with voxel-based morphometry to detect alterations in gray matter volume between groups. Correlation analysis was performed to identify the possible association between depressive symptoms, brain structures and gut microbiota. We found a significant difference in the gut microbial composition between patients with late-life depression (LLD) and healthy controls. The genera Enterobacter and Burkholderia were positively correlated with depressive symptoms and negatively correlated with brain structural signatures in regions associated with memory, somatosensory integration, and emotional processing/cognition/regulation. Our study purports the microbiota-gut-brain axis as a potential mechanism mediating the symptomatology of LLD patients, which may facilitate the development of therapeutic strategies targeting gut microbes in the treatment of elderly depressed patients.

Gut Dysbiosis: A Review of the Effects of a High‐Fat Diet on Iron Regulation and Brain‐Derived Neurotrophic Factor (BDNF) Expression in the Brain‐Gut Axis

IntroductionThe human microbiome in relation to the ‘gut‐brain’ bi‐directional axis is becoming increasingly relevant in our study to understand the effects of gastro‐intestinal microbiota on brain development and neurological diseases such as Alzheimer’s disease. One particular protein of interest is called brain‐derived neurotrophic factor (BDNF), which is a protein found in the brain that is important for learning and memory through stabilization of long‐term potentiation (LTP). Through past research, its expression levels have been found to be greatly affected by diet and exercise. Furthermore, in events such as aging, decreased levels of BDNF is associated with cognitive decline and increased susceptibility to neurodegenerative diseases such as Alzheimer’s disease (AD). Our study aims to look at how the human microbiome, particularly that of a Western diet, affects BDNF expression levels and modulation in the ‘gut‐brain’ bi‐directional axis.MethodsIn order to explore our research topic further, we conducted a literature review of about 80 papers using keywords: Small intestines, brain, liver, hepcidin, TMAO, BDNF, iron, astrocytes, Western Diet, microbiota, gut microbiome, gut dysbiosis, iron, inflammation, oxidative stress, IL‐6, vagus nerve.ResultsAfter reviewing papers, it was concluded that a Western diet decreases brain BDNF expression. However, the exact mechanism of how gut microbiota modulates this expression and function in the brain is unclear. Some papers mentioned BDNF in the gut and the periphery, but not much else other than that they existed.ConclusionsThis study sparked further questions: Does gut microbiota affect brain BDNF directly through the gut‐brain axis? Or is it indirect through an intermediate such as gut BDNF? Is there a relationship between gut BDNF and brain BDNF? It is known that brain BDNF is associated with learning and memory and is important for preserving cognitive abilities, however little is known about how gut microbiota affects it through the gut‐brain axis or even its relation to other peripheral BDNF. Looking forward, we plan on measuring different protein levels, including that of BDNF, in the brains and guts across different cohorts of mice. The cohorts will differ in diet, age, and having the APP gene. From this analysis we hope to find more insight on the unknown mechanism that bridges gut microbiota to BDNF in the brain, which may ultimately help in finding ways to prevent cognitive decline seen in many neurological diseases.

Chemopreventive and hepatoprotective effects of genistein via inhibition of oxidative stress and the versican/PDGF/PKC signaling pathway in experimentally induced hepatocellular carcinoma in rats by thioacetamide

ABSTRACT Objective: Genistein is a recognized isoflavone present in soybeans with antioxidant, anti-inflammatory, antiangiogenic and antitumor activities. This study aimed to test ability of genistein in modulating versican/platelet derived growth factor (PDGF) axis in HCC. Methods: HCC was experimentally induced in male Sprague-Dawley rats then treated with 25 or 75 mg/kg genistein. Antioxidant activities of genistein was assessed by measuring the gene expression of Nrf2 and the hepatic levels of malondialdehyde (MDA), superoxide dismutase (SOD) and reduced glutathione. Expression of versican, PDGF, protein kinase C (PKC) and ERK-1 protein was assessed by Western blotting and immunostaining. Results: HCC induced an elevation in oxidative stress, PDGF, versican, PKC and ERK protein expression levels. Genistein significantly reduced an HCC-induced increase in oxidative stress. Moreover, genistein dose-dependently reduced HCC-induced elevation of PDGF, versican, PKC and ERK protein expression levels. Moreover, genistein helped retain a normal hepatocyte structure and reduced fibrous tissue deposition, especially in high dose. Conclusions: Genistein exerted antitumor and antioxidant effects and therefore suppress HCC development via inhibition of the PDGF/versican bidirectional axis, suppressing both ERK1 and PKC as downstream regulators. Therefore, genistein is a potential novel therapeutic candidate for improving the outcome of patients with HCC. Highlights Genistein is an isoflavones present in various soybeans and soy products. Genistein produced antitumor activity not only due to its antioxidant activity. Genistein expression of versican, PDGF, PKC and ERK. Genistein produced hepatoprotective effects.

Altered Gut Microbial Load and Immune Activation in a Drosophila Model of Human Tauopathy.

Tau is a microtubule-associated protein that stabilizes the neuronal cytoskeleton. In the family of neurodegenerative diseases known as tauopathies, including Alzheimer’s disease (AD), frontotemporal dementia (FTD), and chronic traumatic encephalopathy (CTE), abnormal tau aggregation destabilizes microtubule structure, contributing to a cascade of cellular processes leading to neuronal cell death. The gut microbiome has increasingly become a target of neurodegenerative disease research since gut microbiome imbalances have been linked to protein aggregation and inflammation through a bidirectional axis linking the gut and brain. Accordingly, the present study examined tau-mediated changes to gut microbiome composition and immune activation in a Drosophila melanogaster model of human mutant tauopathy. Fecal deposit quantification and gastric emptying time courses suggested an abnormal food distribution and reduced gut motility in tau transgenic flies compared to controls. Tau transgenic flies also showed an increase in gut bacteria colony forming units (CFUs) from diluted fly homogenate, indicating an increased bacterial load. Finally, we showed that tau transgenic flies have a trend towards elevated systemic levels of antimicrobial peptides targeting gram-negative bacteria using qPCR, suggesting an enhanced innate immune response to bacterial insult. These data demonstrate qualifiable and quantifiable gut microbial and innate immune responses to tauopathy. Furthermore, these results provide a framework for future studies targeting the gut microbiome as a modifier of neurodegenerative disease.

The Role of the Microbiota-Gut-Brain Axis in the Health and Illness Condition: A Focus on Alzheimer's Disease.

Trillions of commensal microbes live in our body, the majority in the gut. This gut microbiota is in constant interaction with the homeostatic systems, the nervous, immune and endocrine systems, being fundamental for their appropriate development and function as well as for the neuroimmunoendocrine communication. The health state of an individual is understood in the frame of this communication, in which the microbiota-gut-brain axis is a relevant example. This bidirectional axis is constituted in early age and is affected by many environmental and lifestyle factors such as diet and stress, among others, being involved in the adequate maintenance of homeostasis and consequently in the health of each subject and in his/her rate of aging. For this, an alteration of gut microbiota, as occurs in a dysbiosis, and the associated gut barrier deterioration and the inflammatory state, affecting the function of immune, endocrine and nervous systems, in gut and in all the locations, is in the base of a great number of pathologies as those that involve alterations in the brain functions. There is an age-related deterioration of microbiota and the homeostatic systems due to oxi-inflamm-aging, and thus the risk of aging associated pathologies such as the neurodegenerative illness. Currently, this microbiota-gut-brain axis has been considered to have a relevant role in the pathogenesis of Alzheimer's disease and represents an important target in the prevention and slowdown of the development of this pathology. In this context, the use of probiotics seems to be a promising help.

Links between biodiversity and human infectious and non-communicable diseases: a review.

Biodiversity has intrinsic value and a fundamental role in human health. The relationship between them is complex, and the specific sustaining processes are still not well understood. In view of the rapidly evolving landscape, this literature review investigated scientific evidence for specific links between biodiversity and human infectious and non-communicable diseases to characterise identifiable relationships. A search of the PubMed and Web of Science databases using keyword algorithms identified relevant manuscripts published between 1 January 2000 and 18 April 2019. Qualitative data were extracted from 155 studies investigating links between or mechanisms linking biodiversity and infectious disease, non-communicable disease, allergic/inflammatory disease and microbiomes. None of the reviewed studies documented causal evidence for a mechanism linking biodiversity and human health. The main mechanisms proposed to link biodiversity and transmission of infectious disease were dilution and amplification. The dilution hypothesis argues that an increase in species diversity leads to a decrease in pathogen prevalence. The amplification effect is the converse, that there is a positive correlation between species diversity and disease risk/infection prevalence. Several driving factors are postulated, including encounter reduction, interspecies competition and predation. In addition, it appears that scale, both spatial and temporal, highly impacts diversity-disease relationships. There is strong evidence that the early environment of a child, including maternally transferred prenatal signals, affects immune maturation, modifying later disease risk. Bi-directional axes communicate between the gut microbiome and the brain, as well as between the skin microbiome and the lung, leading to direct and indirect immune, humoral and neural mechanisms. The main challenges in assessing links between biodiversity and human health are the wide variation in definitions of health and biodiversity, and the heterogeneity in types of studies encountered, as well as the complexity of interactions in dynamic systems. Contextually adapted integrative approaches, which maintain dialogue across disciplines and amongst all stakeholders, are most likely to generate robust evidence. Because of the relevance of local scale, research engagement must occur across levels to generate legitimate practices and translate into sustainable, equitable policies. Recommendations for future action include: improve the knowledge base on contribution of biodiversity to health, increase awareness of health effects of natural and near-natural environments and biodiversity, and promote synergies by increasing policy coherence.

A review on preventive role of ketogenic diet (KD) in CNS disorders from the gut microbiota perspective.

The gut microbiota plays an important role in neurological diseases via the gut-brain axis. Many factors such as diet, antibiotic therapy, stress, metabolism, age, geography and genetics are known to play a critical role in regulating the colonization pattern of the microbiota. Recent studies have shown the role of the low carbohydrate, adequate protein, and high fat "ketogenic diet" in remodeling the composition of the gut microbiome and thereby facilitating protective effects in various central nervous system (CNS) disorders. Gut microbes are found to be involved in the pathogenesis of various CNS disorders like epilepsy, Parkinson's disease (PD), Alzheimer's disease (AD), autism spectrum disorders (ASDs), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and stress, anxiety and depression. Invivo studies have shown an intricate link between gut microbes and KD and specific microbes/probiotics proved useful in invivo CNS disease models. In the present review, we discuss the gut-brain bidirectional axis and the underlying mechanism of KD-based therapy targeting gut microbiome in invivo animal models and clinical studies in neurological diseases. Also, we tried to infer how KD by altering the microbiota composition contributes towards the protective role in various CNS disorders. This review helps to uncover the mechanisms that are utilized by the KD and gut microbiota to modulate gut-brain axis functions and may provide novel opportunities to target therapies to the gut to treat neurologic disorders.

The Dialogue between the Intestine-brain Axis: What is the Role of Probiotics?

Introduction: Communication between intestine-brain axis is complex and uses different pathways. This communication forms a bidirectional axis whose equilibrium depends on the composition of the microbial community that inhabits the intestines. This ecosystem has a modulator role on the intestine-brain axis. Because of this, intestine-brain axis becomes a fascinating growing study area. The intestinal dysbiosis hurts the host's health and can lead to several psychiatric diseases.
 Aim: The present opinion described highlight an emerging theme in medicine, the interesting communication that is established between the intestine-brain axis. The function that intestinal probiotic microorganisms play in the health and disease of the host's has been gaining prominence. This is a promising area with an increasing number of studies which demonstrates its importance.
 Conclusion: In this context, the new class of probiotic microorganisms "psychobiotic" appear to have a significant role in the maintenance of eubiosis, revealing a new therapeutic potential for mental health.

Desired Turbulence? Gut-Lung Axis, Immunity, and Lung Cancer.

The microbiota includes different microorganisms consisting of bacteria, fungi, viruses, and protozoa distributed over many human body surfaces including the skin, vagina, gut, and airways, with the highest density found in the intestine. The gut microbiota strongly influences our metabolic, endocrine, and immune systems, as well as both the peripheral and central nervous systems. Recently, a dialogue between the gut and lung microbiota has been discovered, suggesting that changes in one compartment could impact the other compartment, whether in relation to microbial composition or function. Further, this bidirectional axis is evidenced in an, either beneficial or malignant, altered immune response in one compartment following changes in the other compartment. Stimulation of the immune system arises from the microbial cells themselves, but also from their metabolites. It can be either direct or mediated by stimulated immune cells in one site impacting the other site. Additionally, this interaction may lead to immunological boost, assisting the innate immune system in its antitumour response. Thus, this review offers an insight into the composition of these sites, the gut and the lung, their role in shaping the immune system, and, finally, their role in the response to lung cancer.

The gut–brain axis – a new key to understand mind–body connection

The gut has been considered a digestive organ until the recent discovery of the gut – brain axis. The gut – brain axis is a connection through which the gut microbes are able to influence and control the emotions as well as the cognition of an individual through neuroimmunoendocrinological pathways. This article puts forth some of the well-established discoveries of the gut – brain axis, explaining the mechanism of action on how gut microbes modulate the formation of the enteric nervous system and the production of neurohormones and chemokines to alter the cognitive performance of the brain and the emotional balance of an individual through neural, immune and endocrine pathways. Moreover, this bidirectional axis acts as a new key to understand the mind – body connection in the future.

Predator–prey coevolution driven by size selective predation can cause anti-synchronized and cryptic population dynamics

Population dynamics and evolutionary dynamics can occur on similar time scales, and a coupling of these two processes can lead to novel population dynamics. Recent theoretical studies of coevolving predator–prey systems have concentrated more on the stability of such systems than on the characteristics of cycles when they are unstable. Here I explore the characteristics of the cycles that arise due to coevolution in a system in which prey can increase their ability to escape from predators by becoming either significantly larger or significantly smaller in trait value (i.e., a bidirectional trait axis). This is a reasonable model of body size evolution in some systems. The results show that antiphase population cycles and cryptic cycles (large population fluctuation in one species but almost no change in another species) can occur in the coevolutionary system but not systems where only a single species evolves. Previously, those dynamical patterns have only been theoretically shown to occur in single species evolutionary models and the coevolutionary model which do not involve a bi-directional axis of adaptation. These unusual dynamics may be observed in predator–prey interactions when the density dependence in the prey species is strong.