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In the United States, autism spectrum disorder (ASD) affects 1 in 33 children and is characterized by atypical social interactions, communication difficulties, and intense, restricted interests. Microbial dysbiosis in the gastrointestinal (GI) tract is frequently observed in individuals with ASD, potentially contributing to behavioral manifestations and correlating with worsening severity. Moreover, dysbiosis may contribute to the increased prevalence of GI comorbidities in the ASD population and exacerbate immune dysregulation, further worsening dysbiosis. Over the past 25 years, research on the impact of microbial manipulation on ASD outcomes has gained substantial interest. Various approaches to microbial manipulation have been preclinically and clinically tested, including antibiotic treatment, dietary modifications, prebiotics, probiotics, and fecal microbiota transplantation. Each method has shown varying degrees of success in reducing the severity of ASD behaviors and/or GI symptoms and varying long-term efficacy. In this review, we discuss these microbiome manipulation methods and their outcomes. We also discuss potential microbiome manipulation early in life, as this is a critical period for neurodevelopment. [ABSTRACT FROM AUTHOR]

The Specialized Center of Research Excellence (SCORE) on sex differences at University of California, Los Angeles (UCLA) has a long track record studying bidirectional interactions between different organs and the brain in health and disease with a strong focus on sex as a biological variable (SABV). While the initial focus was on brain-gut interactions in irritable bowel syndrome (IBS), one of the most common disorders of gut-brain interaction, the scope of our Centers research has expanded to a range of different diseases, including inflammatory bowel disease, alcohol use disorder, obesity, urological chronic pelvic pain syndrome, and vulvodynia. This expansion of research focused on the role of brain-body and brain-gut microbiome interactions in these various disorders, aligning well with the increasing importance of multidisciplinary and interdisciplinary team science. The SCOREs Career Enhancement Core (CEC) has modeled team science as applied to SABV research, with educational and training opportunities, a mentoring program, seed grant funding, and other career development experiences that enable mentees to work across the disciplines involved in brain body research. The CEC goals are: (1) To provide seed grant funds for innovative research relevant to the overall SCORE mission and research program; (2) to recruit and foster the career development of students, trainees, and junior investigators who conduct research focused on sex differences or womens health in IBS and chronic constipation and other brain-gut disorders; (3) to facilitate and promote collaboration between the UCLA SCORE and other academic programs involved in womens health education and research; and (4) to promote the importance of SABV through community outreach using collaborative and innovative approaches. These goals focus on establishing the leading research center in sex differences in basic, translational, and clinical aspects of brain-body interactions and on providing women and underrepresented individuals with research opportunities needed to become independent investigators.

A recent opinion article suggested that the target article, "The holobiont mind: A bridge between 4E cognition and the microbiome", wished to generate a "new theory of mind". Furthermore, it contained ideas that were "unnecessary", "not justified", and "not innovative at all". Furthermore the commentators consider that "the ideas of radical enactivism can properly accommodate this research". Here, we address and clarify apprehensions, misreadings, and misunderstandings raised by the commentators. [ABSTRACT FROM AUTHOR]

All life on earth is intrinsically linked. At the very foundation of every evolutionary interaction are microorganisms, integral components in the composition of both organisms and ecosystems. The available data and this perspective on the order of life challenge the traditional conception of monogenetic biological individuals, suggesting living beings are actually composite multi-species complexes : holobionts. In the present article, we introduce our perspective on the concept of the holobiont mind, a biogenic conception of cognition compatible with the 4E approach and the holobiont theory. We furthermore expand on the idea of the mind as the emerging product of multi-genomic morphology of a composite animal-agent, in ever-changing interaction with its ecological niche. We thus briefly review recent evidence on the brain–gut–microbiome axis and the Microbiome of the Built Environment in order to provide a bridge between the Holobiont Mind and the 4E approach to Cognition, two complementary lines of evidence that have not been linked before, opening novel venues for research with direct impact on health and disease. [ABSTRACT FROM AUTHOR]

Neurogastroenterology and motility is a new but advanced subspecialty within gasteroenterology that cater to difficult, persistent and refractory gut-brain symptoms. Hospital USM has the country's first and new state-of-the art motility lab that was recently launched on the 25 May 2023, and is covered in nationwide media. Another first is the Brain-Gut Clinic, established on the 16 November 2022. The clinic is a new concept that builds on unique multiple disciplines in relation to the gut-brain axis. It is hoped that there will be more awareness on the existence of neurogastroenterology and motility among doctors and community, and that more research can be forthcoming to reduce the disease burden. [ABSTRACT FROM AUTHOR]

The discovery of somatostatin (SST) in the hypothalamus implicated the peptide in the inhibition of growth hormone release. However, as observed for numerous neuropeptides, SST was neither restricted to this one brain site nor to this one function. Subsequent studies established a widespread but specific expression of SST in the central nervous system of rodents and humans along with the expression patterns of five receptors (sst1-5 ). Among biological actions, the activation of central SST signaling induced a robust stimulation of food and water intake, which is mediated by the sst2 as assessed using selective sst agonists. The past years have witnessed the identification of brain SST circuitries involved using chemogenetic and optogenetic approaches and further established a physiological orexigenic role of brain SST signaling. The present review will discuss these recent findings.

Objective: Severe gastrointestinal lesions are associated with a poor prognosis in eosinophilic granulomatosis with polyangiitis (EGPA). The goal of this study was to develop an effective predictive model for gastrointestinal lesions and to examine clinical patterns, associated factors, treatment, and outcomes of gastrointestinal lesions in EGPA., Methods: We retrospectively enrolled 165 EGPA patients. The independent associated factors were analyzed using multivariate logistic regression. A nomogram was conducted to quantify the predictive factors. The correlation between different organ lesions was calculated to explore the clinical patterns., Results: A total of 52 patients had gastrointestinal lesions, and 22 developed severe disorders. Common manifestations included abdominal pain (78%), diarrhea (40.4%), and nausea and/or vomiting (32.7%). Severe gastrointestinal lesions included hemorrhage (26.9%), ulcers (17.3%), obstruction (9.6%), and pancreatitis (5.8%). Eosinophilic tissue infiltration, weight loss, and myalgia were independently associated with gastrointestinal involvement. Patients with severe gastrointestinal lesions had a shorter duration from initial symptoms to EGPA diagnosis, less frequent asthma, and ear-nose-throat involvement, and were more likely to receive methylprednisolone pulse. Weight loss, central nervous system involvement, myalgia, and eosinophilic tissue infiltration were retained in the nomogram. An eosinophil ratio of over 19.2% identified gastrointestinal lesions. Significantly more patients with gastrointestinal involvement had a Five Factor Score ≥ 2. Five well-defined clinical models were identified, including the brain-gut pattern., Conclusions: Severe gastrointestinal lesions are common in EGPA and early detection is critical. Eosinophils are an important factor associated with gastrointestinal involvement of EGPA. We developed a model to predict the risk of gastrointestinal lesions. The brain-gut pattern might deserve further investigation in EGPA., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of PUMCH (number S-K1385, Beijing, China). As a retrospective study, the patient consent was not required but their privacy was protected well. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

In May 2014, the National Institutes of Health (NIH) stated its intent to "require applicants to consider sex as a biological variable (SABV) in the design and analysis of NIH-funded research involving animals and cells." Since then, proposed research plans that include animals routinely state that both sexes/genders will be used; however, in many instances, researchers and reviewers are at a loss about the issue of sex differences. Moreover, the terms sex and gender are used interchangeably by many researchers, further complicating the issue. In addition, the sex or gender of the researcher might influence study outcomes, especially those concerning behavioral studies, in both animals and humans. The act of observation may change the outcome (the "observer effect") and any experimental manipulation, no matter how well-controlled, is subject to it. This is nowhere more applicable than in physiology and behavior. The sex of established cultured cell lines is another issue, in addition to aneuploidy; chromosomal numbers can change as cells are passaged. Additionally, culture medium contains steroids, growth hormone, and insulin that might influence expression of various genes. These issues often are not taken into account, determined, or even considered. Issues pertaining to the "sex" of cultured cells are beyond the scope of this Statement. However, we will discuss the factors that influence sex and gender in both basic research (that using animal models) and clinical research (that involving human subjects), as well as in some areas of science where sex differences are routinely studied. Sex differences in baseline physiology and associated mechanisms form the foundation for understanding sex differences in diseases pathology, treatments, and outcomes. The purpose of this Statement is to highlight lessons learned, caveats, and what to consider when evaluating data pertaining to sex differences, using 3 areas of research as examples; it is not intended to serve as a guideline for research design. [ABSTRACT FROM AUTHOR]

Communication between the central nervous system (CNS) and the gastrointestinal tract is called the brain-gut axis. This communication network includes the CNS, hypothalamic-pituitary-adrenal axis, the autonomic nervous system (sympathetic and parasympathetic), the enteric nervous system and the gut microbiota. From the conditioned reflex activity in gastric acid secretion discovered by Pavlov to the recognition of the role of CNS in stress-induced gastric ulcer and exacerbation of intestinal inflammation, all these facts confirm the significance of brain-gut axis. Moreover, mental illnesses and depression also result in high risk for developing subsequent gastrointestinal mucosal injury. The brain-gut axis is bidirectional; therefore, not only the CNS affects the gastrointestinal functions, but the gut information is also forwarded to the CNS, which may modify its activity. Several observations suggested that changes in microbiome composition can be manifested in alterations of behavior and cognition; and a strong correlation between dysbiosis and psychiatric disorders has been observed. These observations substantially contributed to the establishment of the concept of the microbiota-gut-brain axis. The present work aims to overview the mutual role of brain-gut-microbiota and microbiota-gut-brain axis in the development of gastrointestinal and mental disorders as well as their mechanisms.

Background: Disruptions of brain-gut axis have been implicated in the progression of a variety of gastrointestinal (GI) disorders and central nervous system (CNS) diseases and injuries, including traumatic brain injury (TBI). TBI is a chronic disease process characterized by persistent secondary injury processes which can be exacerbated by subsequent challenges. Enteric pathogen infection during chronic TBI worsened cortical lesion volume; however, the pathophysiological mechanisms underlying the damaging effects of enteric challenge during chronic TBI remain unknown. This preclinical study examined the effect of intestinal inflammation during chronic TBI on associated neurobehavioral and neuropathological outcomes, systemic inflammation, and dysautonomia.Methods: Dextran sodium sulfate (DSS) was administered to adult male C57BL/6NCrl mice 28 days following craniotomy (Sham) or TBI for 7 days to induce intestinal inflammation, followed by a return to normal drinking water for an additional 7 to 28 days for recovery; uninjured animals (Naïve) served as an additional control group. Behavioral testing was carried out prior to, during, and following DSS administration to assess changes in motor and cognitive function, social behavior, and mood. Electrocardiography was performed to examine autonomic balance. Brains were collected for histological and molecular analyses of injury lesion, neurodegeneration, and neuroinflammation. Blood, colons, spleens, mesenteric lymph nodes (mLNs), and thymus were collected for morphometric analyses and/or immune characterization by flow cytometry.Results: Intestinal inflammation 28 days after craniotomy or TBI persistently induced, or exacerbated, respectively, deficits in fine motor coordination, cognition, social behavior, and anxiety-like behavior. Behavioral changes were associated with an induction, or exacerbation, of hippocampal neuronal cell loss and microglial activation in Sham and TBI mice administered DSS, respectively. Acute DSS administration resulted in a sustained systemic immune response with increases in myeloid cells in blood and spleen, as well as myeloid cells and lymphocytes in mesenteric lymph nodes. Dysautonomia was also induced in Sham and TBI mice administered DSS, with increased sympathetic tone beginning during DSS administration and persisting through the first recovery week.Conclusion: Intestinal inflammation during chronic experimental TBI causes a sustained systemic immune response and altered autonomic balance that are associated with microglial activation, increased neurodegeneration, and persistent neurological deficits. [ABSTRACT FROM AUTHOR]

There is a growing interest in the identification of molecules capable to promote health and with a concurrent potential for technological applications. Prebiotics are functional ingredients naturally occurring in some plant and animal foods that since many decades stimulated considerable attention from the pharmaceutical and food industries due to their positive health effects. Together the well-known biomolecules with ascertained prebiotic effect, in last year new molecules were finally recognized as prebiotics, so capable to improve the health of an organism, also through the positive effect exerted on host microbiota. Among the so-called prebiotics, a special mention should be given to polyphenols, probably the most important, or at least among the most important secondary metabolites produced by the vegetal kingdom. This short chapter wants to emphasize polyphenols and, after briefly describing the individual microbiome, to illustrate how polyphenols can, through their influence on the microbiome, have a positive effect on the health of the individual in general, and on some pathologies in particular, for which the role of a bad status of the individual microbiome has been definitively established. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) comorbidities are common in individuals with mood and behavioral dysfunction. Similarly, patients with GI problems more commonly suffer from co-morbid psychiatric diagnoses. Although the central and enteric nervous systems (CNS and ENS, respectively) have largely been studied separately, there is emerging interest in factors that may contribute to disease states involving both systems. There is strong evidence to suggest that serotonin may be an important contributor to these brain-gut conditions. Serotonin has long been recognized for its critical functions in CNS development and function. The majority of the body’s serotonin, however, is produced in the GI tract, where it plays key roles in ENS development and function. Further understanding of the specific impact that enteric serotonin has on brain-gut disease may lay the foundation for the creation of novel therapeutic targets. This review summarizes the current data focusing on the important roles that serotonin plays in ENS development and motility, with a focus on novel aspects of serotonergic signaling in medical conditions in which CNS and ENS co-morbidities are common, including autism spectrum disorders and depression. [ABSTRACT FROM AUTHOR]

The present randomized double-blinded cross-over study aims to extensively study the neural correlates underpinning cognitive functions in healthy subjects after acute glucose and fructose administration, using an integrative multimodal neuroimaging approach. Five minutes after glucose, fructose, or placebo administration through a nasogastric tube, 12 participants underwent 3 complementary neuroimaging techniques: 2 task-based functional magnetic resonance imaging (fMRI) sequences to assess working memory (N-back) and response inhibition (Go/No-Go) and one resting state fMRI sequence to address the cognition-related fronto-parietal network (FPN) and salience network (SN). During working memory processing, glucose intake decreased activation in the anterior cingulate cortex (ACC) relative to placebo, while fructose decreased activation in the ACC and sensory cortex relative to placebo and glucose. During response inhibition, glucose and fructose decreased activation in the ACC, insula and visual cortex relative to placebo. Resting state fMRI indicated increased global connectivity strength of the FPN and the SN during glucose and fructose intake. The results demonstrate that glucose and fructose lead to partially different partially overlapping changes in regional brain activities that underpin cognitive performance in different tasks.

The importance of gut microbiota in gastrointestinal (GI) physiology was well described, but our ability to study gut microbial ecosystems in their entirety was limited by culture-based methods prior to the sequencing revolution. The advent of high-throughput sequencing opened new avenues, allowing us to study gut microbial communities as an aggregate, independent of our ability to culture individual microbes. Early studies focused on association of changes in gut microbiota with different disease states, which was necessary to identify a potential role for microbes and generate novel hypotheses. Over the past few years the field has moved beyond associations to better understand the mechanistic implications of the microbiome in the pathophysiology of complex diseases. This movement also has resulted in a shift in our focus toward therapeutic strategies, which rely on better understanding the mediators of gut microbiota–host cross-talk. It is not surprising the gut microbiome has been implicated in the pathogenesis of functional gastrointestinal disorders given its role in modulating physiological processes such as immune development, GI motility and secretion, epithelial barrier integrity, and brain–gut communication. In this review, we focus on the current state of knowledge and future directions in microbiome research as it pertains to functional gastrointestinal disorders. We summarize the factors that help shape the gut microbiome in human beings. We discuss data from animal models and human studies to highlight existing paradigms regarding the mechanisms underlying microbiota-mediated alterations in physiological processes and their relevance in human interventions. While translation of microbiome science is still in its infancy, the outlook is optimistic and we are advancing in the right direction toward precise mechanism-based microbiota therapies. [ABSTRACT FROM AUTHOR]

Activity-based anorexia (ABA) is a well-established animal model mimicking the eating disorder anorexia nervosa (AN). Since the pathophysiology of AN is yet poorly understood and specific drug treatments are lacking so far, animal models might be useful to further understand this disease. ABA consists of time-restricted access to food for 1.5 h/day and the possibility to exercise in a running wheel for 24 h/day. This combination leads to robust body weight loss as observed in AN. Here, we investigated the activation of brain corticotropin-releasing factor (CRF) neurons, a transmitter involved in the response to stress, emotional processes and also food intake. After development of ABA, rat brains were processed for c-Fos and CRF double immunohistochemistry. ABA increased the number of c-Fos/CRF double labeled neurons in the paraventricular nucleus (PVN) and the dorsomedial hypothalamic nucleus (DMH) compared to the ad libitum (AL, ad libitum fed, no running wheel) and activity (AC, ad libitum fed, running wheel, p  < 0.05) but not to the restricted feeding (RF, food for 1.5 h/day, no running wheel, p  > 0.05) group. Also the number of CRF neurons was increased in the DMH of ABA rats compared to AL and AC ( p  < 0.05). In the Edinger-Westphal nucleus (EW) the number of c-Fos positive neurons was increased in ABA and RF compared to AC ( p  < 0.05), while the number of double labeled neurons was not different ( p  > 0.05). Taken together, brain CRF activated under conditions of ABA might play a role in the development and maintenance of this animal model and possibly also in human AN. [ABSTRACT FROM AUTHOR]

The present randomized double-blinded cross-over study aims to extensively study the neural correlates underpinning cognitive functions in healthy subjects after acute glucose and fructose administration, using an integrative multimodal neuroimaging approach. Five minutes after glucose, fructose, or placebo administration through a nasogastric tube, 12 participants underwent 3 complementary neuroimaging techniques: 2 task-based functional magnetic resonance imaging (fMRI) sequences to assess working memory (N-back) and response inhibition (Go/No-Go) and one resting state fMRI sequence to address the cognition-related fronto-parietal network (FPN) and salience network (SN). During working memory processing, glucose intake decreased activation in the anterior cingulate cortex (ACC) relative to placebo, while fructose decreased activation in the ACC and sensory cortex relative to placebo and glucose. During response inhibition, glucose and fructose decreased activation in the ACC, insula and visual cortex relative to placebo. Resting state fMRI indicated increased global connectivity strength of the FPN and the SN during glucose and fructose intake. The results demonstrate that glucose and fructose lead to partially different partially overlapping changes in regional brain activities that underpin cognitive performance in different tasks. [ABSTRACT FROM AUTHOR]

Activity-based anorexia (ABA) is an established animal model for the eating disorder anorexia nervosa (AN). The pathophysiology of AN and the involvement of food intake-regulatory peptides is still poorly understood. Nesfatin-1, an anorexigenic peptide also involved in the mediation of stress, anxiety and depression might be a likely candidate involved in the pathogenesis of AN. Therefore, activation of nesfatin-1 immunoreactive (ir) brain nuclei was investigated under conditions of ABA. Female Sprague-Dawley rats were used and divided into four groups (n = 6/group): activity-based anorexia (ABA), restricted feeding (RF), activity (AC) and ad libitum fed (AL). After the 21-day experimental period and development of ABA, brains were processed for c-Fos/nesfatin-1 double labeling immunohistochemistry. ABA increased the number of nesfatin-1 immunopositive neurons in the paraventricular nucleus, arcuate nucleus, dorsomedial hypothalamic nucleus, locus coeruleus and in the rostral part of the nucleus of the solitary tract compared to AL and AC groups ( p < 0.05) but not to RF rats ( p > 0.05). Moreover, we observed significantly more c-Fos and nesfatin-1 ir double-labeled cells in ABA rats compared to RF, AL and AC in the supraoptic nucleus ( p < 0.05) and compared to AL and AC in the paraventricular nucleus, arcuate nucleus, dorsomedial hypothalamic nucleus, dorsal raphe nucleus and the rostral raphe pallidus ( p < 0.05). Since nesfatin-1 plays a role in the inhibition of food intake and the response to stress, we hypothesize that the observed changes of brain nesfatin-1 might play a role in the pathophysiology and symptomatology under conditions of ABA and potentially also in patients with AN. [ABSTRACT FROM AUTHOR]

Phoenixin is a pleiotropic peptide involved in reproduction, anxiety and recently also implicated in the control of food intake. Besides the 20-amino acid phoenixin, the 14-amino acid phoenixin-14 also shows bioactive properties. However, the expression sites of phoenixin-14 in the brain and peripheral tissues are not yet described in detail. Therefore, a mapping of the brain and peripheral tissues from male and female Sprague-Dawley rats with a specific phoenixin-14 antibody was performed using western blot and immunohistochemistry. High density of phoenixin-14 immunoreactivity was detected in the medial division of the brain central amygdaloid nucleus, in the spinal trigeminal tract and in the spinocerebellar tract as well as in cells between the crypts of duodenum, jejunum and ileum. Medium density immunoreactivity was observed in the bed nucleus of the stria terminalis, in the area postrema, the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve as well as in the peripheral parts of the islets of Langerhans in the pancreas. A low density of phoenixin-14 immunoreactivity was detected in the arcuate nucleus, the supraoptic nucleus and the raphe pallidus. After pre-absorption of the antibody with phoenixin-14 peptide, no immunosignals were observed indicating specificity of the antibody. Taken together, the widespread distribution of phoenixin-14 immunoreactivity gives additional rise to the pleiotropic functions of the peptide such as possible effects in gastrointestinal motility, immune functions and glucose homeostasis. [ABSTRACT FROM AUTHOR]

Nesfatin-1 was discovered a decade ago and despite the fact that it represents just one of a multitude of food intake-inhibiting factors it received increasing attention. This led to a detailed characterization of NUCB2/nesfatin-1's physiological property to reduce food intake and also gave rise to an involvement in the long term regulation of body weight, especially under conditions of obesity. In addition, studies indicated the involvement of NUCB2/nesfatin-1 in other homeostatic functions as well: glucose homeostasis, water intake, gastrointestinal functions, temperature regulation, cardiovascular functions, puberty onset and sleep. These pleiotropic actions underline the physiological relevance of this peptide. Recently, the involvement of NUCB2/nesfatin-1 in psychiatric disorders such as anxiety has been investigated giving rise to the speculation that NUCB2/nesfatin-1 represents a peptidergic link between eating and anxiety/depression disorders. [ABSTRACT FROM AUTHOR]

Stress responses to physical, psychological, environmental, or cellular stressors, has two arms: initiation and recovery. Corticotropin-releasing factor (CRF) is primarily responsible for regulating and/or initiating stress responses via, whereas urocortins (UCNs) are involved in the recovery response to stress via feedback inhibition. Stress is a loaded, polysemous word and is experienced in a myriad of ways. Some stressors are good for an individual, in fact essential, whereas other stressors are associated with bad outcomes. Perceived stress, like beauty, lies in the eye of the beholder, and hence the same stressor can result in individual-specific outcomes. In mammals, there are two main biological sexes with reproduction as primary function. Reproduction and nutrition can also be viewed as stressors; based on a body of work from my laboratory, we propose that the functions of all other organs have co-evolved to optimize and facilitate an individual's nutritional and reproductive functions. Hence, sex differences in physiologically relevant outcomes are innate and occur at all levels- molecular, endocrine, immune, and (patho)physiological. CRF and three UCNs are peptide hormones that mediate their physiological effects by binding to two known G protein-coupled receptors (GPCRs), CRF 1 and CRF 2 . Expression and function of CRF family of hormones and their receptors is likely to be sexually dimorphic in all organs. In this chapter, based on the large body of work from others and my laboratory, an overview of the CRF family with special emphasis on sex-specific actions of peripherally expressed CRF 2 receptor in health and disease is provided., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Brain-gut dysfunction has been implicated in gastrointestinal disorders but a comprehensive test of brain-gut axis is lacking. We developed and tested a novel method for assessing both afferent anorectal-brain function using cortical evoked potentials (CEP), and efferent brain-anorectal function using motor evoked potentials (MEP). Cortical evoked potentials was assessed following electrical stimulations of anus and rectum with bipolar electrodes in 26 healthy subjects. Anorectal MEPs were recorded following transcranial magnetic stimulation (TMS) over paramedian motor cortices bilaterally. Anal and rectal latencies/amplitudes for CEP and MEP responses and thresholds for first sensation and pain (mA) were analyzed and compared. Reproducibility and interobserver agreement of responses were examined. Reproducible polyphasic rectal and anal CEPs were recorded in all subjects, without gender differences, and with negative correlation between BMI and CEP amplitude (r −0.66, P = 0.001). Transcranial magnetic stimulation evoked triphasic rectal and anal MEPs, without gender differences. Reproducibility for CEP and MEP was excellent (CV <10%). The inter-rater CV for anal and rectal MEPs was excellent (ICC 97-99), although there was inter-subject variation. Combined CEP and MEP studies offer a simple, inexpensive and valid method of examining bidirectional brain-anorectal axes. This comprehensive method could provide mechanistic insights into lower gut disorders. [ABSTRACT FROM AUTHOR]

Abstract: Nesfatin-1 is an 82 amino acid peptide recently discovered in the brain which is derived from nucleobindin2 (NUCB2), a protein that is highly conserved across mammalian species. Nesfatin-1 has received much attention over the past two years due to its reproducible food intake-reducing effect that is linked with recruitment of other hypothalamic peptides regulating feeding behavior. A growing amount of evidence also supports that various stressors activate fore- and hindbrain NUCB2/nesfatin-1 circuitries. In this review, we outline the central nervous system distribution of NUCB2/nesfatin-1, and recent developments on the peripheral expression of NUCB2/nesfatin-1, in particular its co-localization with ghrelin in gastric X/A-like cells and insulin in ß-cells of the endocrine pancreas. Functional studies related to the characteristics of nesfatin-1''s inhibitory effects on dark phase food intake are detailed as well as the central activation of NUCB2/nesfatin-1 immunopositive neurons in the response to psychological, immune and visceral stressors. Lastly, potential clinical implications of targeting NUCB2/nesfatin-1 signaling and existing gaps in knowledge to ascertain the role and mechanisms of action of nesfatin-1 are presented. [Copyright &y& Elsevier]

Abstract: The present study analyses the expression and distribution of neuronal nitric oxide synthase (nNOS) in the brainstem of animals pre-treated with Escherichia coli or Helicobacter pylori LPS, at doses that modulate gastric motor function. Systemic administration of H. pylori LPS prevented in a dose-dependent manner (5, 40 and 100 μg kg−1, i.v.) the increase in intragastric pressure induced by 2-deoxy-d-glucose (200 mg kg−1, i.v.) in urethane-anaesthetized rats. Quantitative analysis showed a significant increase in the amount of nNOS mRNA induced by E. coli or H. pylori LPS (2 h later), in a segment of the brainstem containing the dorsal vagal complex (DVC). Immunohistochemical studies showed nNOS presence in the DVC of vehicle-treated rats. Both E. coli (40 μg kg−1, i.p.) and H. pylori LPS (100 μg kg−1, i.p.) significantly increased (2 h later) the number of nNOS immunoreactive cells in this area, mainly at the most rostral level. The present study shows that systemic administration of E. coli or H. pylori LPS induces a transcriptional up-regulation of the nNOS in the DVC of the brainstem and suggests a role for NO synthesis in this area in the control of gastric motor function under endotoxemia. [Copyright &y& Elsevier]

• Restraint stress activates and induces a significant increase of phoenixin expression in several nuclei. • Phoenixin expression and activity are positively correlated in the RPa, DMN and mNTS. • Phoenixin possibly has a counter-balancing role in a negative feedback loop with nesfatin-1 to manage reactions to stress. Phoenixin is a recently discovered peptide, which has been associated with reproduction, anxiety and food intake. Based on a considerable co-localization it has been linked to nesfatin-1, with a possible antagonistic mode of action. Since nesfatin-1 is known to play a role in anxiety and the response to stress, this study aims to investigate the effects of a well-established psychological stress model, restraint stress, on phoenixin-expressing brain nuclei and phoenixin expression in rats. Male Sprague-Dawley rats were subjected to restraint stress (n = 8) or left undisturbed (control, n = 6) and the brains processed for c-Fos- and phoenixin immunohistochemistry. The number of c-Fos expressing cells was counted and phoenixin expression assessed semiquantitatively. Restraint stress significantly increased c-Fos expression in the dorsal motor nucleus of vagus nerve (DMN, 52-fold, p < 0.001), raphe pallidus (RPa, 15-fold, p < 0.001), medial part of the nucleus of the solitary tract (mNTS, 16-fold, p < 0.001), central amygdaloid nucleus, medial division (CeM, 9-fold, p = 0.01), supraoptic nucleus (SON, 9-fold, p < 0.001) and the arcuate nucleus (Arc, 2.5-fold, p < 0.03) compared to control animals. Also phoenixin expression significantly increased in the DMN (17-fold, p < 0.001), RPa (2-fold, p < 0.001) and mNTS (1.6-fold, p < 0.001) with positive correlations between c-Fos and phoenixin (r = 0.74–0.85; p < 0.01) in these nuclei. This pattern of activation suggests an involvement of phoenixin in response to restraint stress. Whether phoenixin mediates stress effects or is activated in a counterbalancing fashion will have to be further investigated. [ABSTRACT FROM AUTHOR]

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 and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson's disease, and Alzheimer's disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. 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.