Molecular signalling during cross talk between gut brain axis regulation and progression of irritable bowel syndrome:A comprehensive review

Irritable bowel syndrome(IBS)is a chronic functional disorder which alters gastrointestinal(GI)functions,thus leading to compromised health status.Pathophysiology of IBS is not fully understood,whereas abnormal gut brain axis(GBA)has been identified as a major etiological factor.Recent studies are suggestive for visceral hyper-sensitivity,altered gut motility and dysfunctional autonomous nervous system as the main clinical abnormalities in IBS patients.Bidirectional signalling interactions among these abnormalities are derived through various exogenous and endogenous factors,such as microbiota population and diversity,microbial metabolites,dietary uptake,and psychological abnormalities.Strategic efforts focused to study these interactions including probiotics,antibiotics and fecal transplantations in normal and germfree animals are clearly suggestive for the pivotal role of gut microbiota in IBS etiology.Additionally,neurotransmitters act as communication tools between enteric microbiota and brain functions,where serotonin(5-hydroxytryptamine)plays a key role in pathophysiology of IBS.It regulates GI motility,pain sense and inflammatory responses particular to mucosal and brain activity.In the absence of a better understanding of various interconnected crosstalks in GBA,more scientific efforts are required in the search of novel and targeted therapies for the management of IBS.In this review,we have summarized the gut microbial composition,interconnected signalling pathways and their regulators,available therapeutics,and the gaps needed to fill for a better management of IBS.

The microbiota-gut-brain axis and neurodevelopmental disorders

The gut microbiota has been found to interact with the brain through the microbiota-gut-brain axis,regulating various physiological processes.In recent years,the impacts of the gut microbiota on neurodevelopment through this axis have been increasingly appreciated.The gut microbiota is commonly considered to regulate neurodevelopment through three pathways,the immune pathway,the neuronal pathway,and the endocrine/systemic pathway,with overlaps and crosstalks in between.Accumulating studies have identified the role of the microbiota-gut-brain axis in neurodevelopmental disorders including autism spectrum disorder,attention deficit hyperactivity disorder,and Rett Syndrome.Numerous researchers have examined the physiological and pathophysiological mechanisms influenced by the gut microbiota in neurodevelopmental disorders(NDDs).This review aims to provide a comprehensive overview of advancements in research pertaining to the microbiota-gut-brain axis in NDDs.Furthermore,we analyzed both the current state of research progress and discuss future perspectives in this field.

Gut microbiota-astrocyte axis: new insights into age-related cognitive decline

With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

Impact of gut–brain interaction in emerging neurological disorders

The central nervous system(CNS)is a reservoir of immune privilege.Specialized immune glial cells are responsible for maintenance and defense against foreign invaders.The blood–brain barrier(BBB)prevents detrimental pathogens and potentially overreactive immune cells from entering the periphery.When the double-edged neuroinflammatory response is overloaded,it no longer has the protective function of promoting neuroregeneration.Notably,microbiota and its derivatives may emerge as pathogen-associated molecular patterns of brain pathology,causing microbiome–gut–brain axis dysregulation from the bottom-up.When dysbiosis of the gastrointestinal flora leads to subsequent alterations in BBB permeability,peripheral immune cells are recruited to the brain.This results in amplification of neuroinflammatory circuits in the brain,which eventually leads to specific neurological disorders.Aggressive treatment strategies for gastrointestinal disorders may protect against specific immune responses to gastrointestinal disorders,which can lead to potential protective effects in the CNS.Accordingly,this study investigated the mutual effects of microbiota and the gut–brain axis,which may provide targeting strategies for future disease treatment.

Not only a bad guy:potential proneurogenic role of the RAGE/NF-κB axis in Alzheimer's disease brain

The receptor for advanced glycation endproducts（RAGE）is a receptor of the immunoglobulin superfamily of cell surface molecules which plays important contributions under both physiological and pathological conditions.Over the years extensive research work supported the detrimental role of RAGE in Alzheimer’s disease（AD）pathophysiology,ranging from its involvement in beta amyloid（Aβ）brain influx and clearance,

Early exposure to food contaminants reshapes maturation of the human brain-gut-microbiota axis

Early childhood growth and development is conditioned by the consecutive events belonging to perinatal programming. This critical window of life will be very sensitive to any event altering programming of the main body functions.Programming of gut function, which is starting right after conception, relates to a very well-established series of cellular and molecular events associating all types of cells present in this organ, including neurons, endocrine and immune cells. At birth, this machinery continues to settle with the establishment of extra connection between enteric and other systemic systems and is partially under the control of gut microbiota activity, itself being under the densification and the diversification of microorganisms’ population. As thus, any environmental factor interfering on this pre-established program may have a strong incidence on body functions. For all these reasons, pregnant women, fetuses and infants will be particularly susceptible to environmental factors and especially food contaminants. In this review, we will summarize the actual understanding of the consequences of repeated low-level exposure to major food contaminants on gut homeostasis settlement and on brain/gut axis communication considering the pivotal role played by the gut microbiota during the fetal and postnatal stages and the presumed consequences of these food toxicants on the individuals especially in relation with the risks of developing later in life non-communicable chronic diseases.

Inhibition of the cGAS–STING pathway:contributing to the treatment of cerebral ischemia-reperfusion injury

The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.

Global research trends in the microbiome related to irritable bowel syndrome: A bibliometric and visualized study

BACKGROUND Irritable bowel syndrome(IBS) is a common functional gastrointestinal disorder. Dysregulation of the gut–brain axis plays a central role in the pathophysiology of IBS. It is increasingly clear that the microbiome plays a key role in the development and normal functioning of the gut–brain axis.AIM To facilitate the identification of specific areas of focus that may be of relevance to future research. This study represents a bibliometric analysis of the literature pertaining to the microbiome in IBS to understand the development of this field.METHODS The data used in our bibliometric analysis were retrieved from the Scopus database. The terms related to IBS and microbiome were searched in titles or abstracts within the period of 2000–2019. VOSviewer software was used for data visualization.RESULTS A total of 13055 documents related to IBS were retrieved at the global level. There were 1872 scientific publications focused on the microbiome in IBS. There was a strong positive correlation between publication productivity related to IBS in all fields and productivity related to the microbiome in IBS(r = 0.951, P < 0.001). The United States was the most prolific country with 449(24%) publications, followed by the United Kingdom(n = 176, 9.4%), China(n = 154, 8.2%), and Italy(n = 151, 8.1%). The h-index for all retrieved publications related to the microbiome in IBS was 138. The hot topics were stratified into four clusters:(1) The gut–brain axis related to IBS;(2) Clinical trials related to IBS and the microbiome;(3) Drugmediated manipulation of the gut microbiome;and(4) The role of the altered composition of intestinal microbiota in IBS prevention.CONCLUSION This is the first study to evaluate and quantify global research productivity pertaining to the microbiome in IBS. The number of publications regarding the gut microbiota in IBS has continuously grown since 2013. This finding suggests that the future outlook for interventions targeting the gut microbiota in IBS remains promising.

A Qualitative Model of the Interaction of Sexual Behavior and Hormone Gene Transcription in Male Blue Gourami during Reproduction

In the present study, a model is suggested to describe hormone control in male blue gourami (Trichogaster trichopterus) along the gonadotropic brain-pituitary- gonad axis (BPG axis) and the hypothalamic-pituitary-somatotropic axis (HPS axis). This model is based on the cloning and transcription of genes encoding hormones of the two axes involved in spermatogenesis during blue gourami reproduction. Gene transcription is affected by environmental, biological, and behavioral factors. Mature males were examined in two different stages—nonreproductive in high-density habitats and reproductive in low-density habitats. Based on gene transcription, gonadotropin-releasing hormone 1 (GnRH1) was involved in controlling spermatogenesis (spermatogonia to spermatids) via the BPG axis in nonreproductive and reproductive stages by controlling follicle-stimulating hormone (FSH), 11-ketotestosterone (11KT) and 17β-estradiol (E2). However, GnRH3 had a larger effect during the reproductive stage via the BPG axis (spermatids to sperm) on luteinizing hormone (LH), 11KT, and 17α-hydroxyprogesterone (17P). At the same time, the HPS axis was involved in spermatogenesis via pituitary adenylate cyclase-activating polypeptide (PACAP) and its related peptide PRP (formerly known as GHRH-like peptide) in the brain, and growth hormone (GH) in the pituitary affected synthesis of insulin-like growth factor 1 (IGF1) in the liver.