Microbial Reprogramming in Obsessive-Compulsive Disorders: A Review of Gut-Brain Communication and Emerging Evidence.

Obsessive-compulsive disorder (OCD) is a debilitating mental health disorder characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions). Dysbiosis, an imbalance in the gut microbial composition, has been associated with various health conditions, including mental health disorders, autism, and inflammatory diseases. While the exact mechanisms underlying OCD remain unclear, this review presents a growing body of evidence suggesting a potential link between dysbiosis and the multifaceted etiology of OCD, interacting with genetic, neurobiological, immunological, and environmental factors. This review highlights the emerging evidence implicating the gut microbiota in the pathophysiology of OCD and its potential as a target for novel therapeutic approaches. We propose a model that positions dysbiosis as the central unifying element in the neurochemical, immunological, genetic, and environmental factors leading to OCD. The potential and challenges of microbial reprogramming strategies, such as probiotics and fecal transplants in OCD therapeutics, are discussed. This review raises awareness of the importance of adopting a holistic approach that considers the interplay between the gut and the brain to develop interventions that account for the multifaceted nature of OCD and contribute to the advancement of more personalized approaches.

Identifying lifestyle factors associated to co-morbidity of obesity and psychiatric disorders, a pilot study.

Obesity and psychiatric disorders are linked through a bidirectional association. Obesity rates have tripled globally in the past decades, and it is predicted that by 2025, one billion people will be affected by obesity, often with a co-morbidity such as depression. While this co-morbidity seems to be a global health issue, lifestyle factors associated to it differ between countries and are often attributed to more than one factor. Prior obesity studies were performed in Western populations; this is the first study that investigates lifestyle factors relating to obesity and mental health of the diverse population in Qatar, a country that has witnessed tremendous lifestyle change in a short time. In this pilot study, we surveyed 379 respondents to assess and compare the lifestyles of Qatar residents to the global population. However due to the high proportion of responses from the United Kingdom (UK) residents, we have made comparisons between Qatar residents and UK residents. We used chi-square analysis, spearman rank correlation and logistic regression to compare the lifestyle factors of individuals suffering from both increased BMI and mental health conditions. The types of food consumed, stress, exercise frequency and duration, alcohol and tobacco consumption, and sleep duration, were explored and results argue that different lifestyle factors can contribute to the same health condition, suggesting different mechanisms involved. We found that both groups reported similar sleep durations (p = 0.800), but that perception of sleep (p = 0.011), consumption of alcohol (p = 0.001), consumption of takeaway food (p = 0.007), and physical activity significantly varied between the groups (p = 0.0001). The study examined the predictors of comorbidity in Qatar as well as UK populations using multivariate logistic regression analysis. The result of the study showed no statistical association between comorbidity and the predictors drinking habit, smoking, physical activity, vegetable consumption, eat outs, and sleep perception for the Qatar population, and for the combined population. This study, however showed a significant association (p = 0.033) between sleep perception and comorbidity for the UK population. We conclude that further analysis is needed to understand the relationship between specific lifestyle factors and multimorbidity in each country.

EEG Correlates of Middle Eastern Music Improvisations on the Ney Instrument.

The cognitive sciences have witnessed a growing interest in cognitive and neural basis of human creativity. Music improvisations constitute an ideal paradigm to study creativity, but the underlying cognitive processes remain poorly understood. In addition, studies on music improvisations using scales other than the major and minor chords are scarce. Middle Eastern Music is characterized by the additional use of microtones, resulting in a tonal-spatial system called Maqam. No EEG correlates have been proposed yet for the eight most commonly used maqams. The Ney, an end-blown flute that is popular and widely used in the Middle East was used by a professional musician to perform 24 improvisations at low, medium, and high tempos. Using the EMOTIV EPOC+, a 14-channel wireless EEG headset, brainwaves were recorded and quantified before and during improvisations. Pairwise comparisons were calculated using IBM-SPSS and a principal component analysis was used to evaluate the variability between the maqams. A significant increase of low frequency bands theta power and alpha power were observed at the frontal left and temporal left area as well as a significant increase in higher frequency bands beta-high bands and gamma at the right temporal and left parietal area. This study reveals the first EEG observations of the eight most commonly used maqam and is proposing EEG signatures for various maqams.

Fecal microbiota transplants: A review of emerging clinical data on applications, efficacy, and risks (2015-2020).

As the importance of the gut microbiota in health and disease is a subject of growing interest, fecal microbiota transplantation (FMT) was suggested as an attractive therapeutic strategy to restore homeostasis of the gut microbiota, thereby treating diseases that were associated with alteration of the gut microbiota. FMT involves the administration of fresh, frozen, or dried fecal microorganisms from the gut of a healthy donor into the intestinal tract of a patient. This rediscovery of the potential benefits of an ancient practice was accompanied by a rapid progression of our understanding of the roles and mechanisms of gut microbes in the pathogenesis of disease. With a growing number of diseases being associated with dysbiosis or the alteration of gut microbiota, FMT was suggested as an attractive therapeutic strategy to "reset the gut" and initiate clinical resolutions or remissions. The number of FMT clinical trials is increasing worldwide, but no trials are registered in the Gulf region; this suggested the need for raising awareness of the latest studies on FMT. This review presented the emergent preclinical and clinical data to give an overview of the potential clinical applications, the benefits, and inconveniences that were worth considering for eventual future testing of fecal transplants in Qatar and the Middle East. This study highlighted the diversity of methods tested and commented on the variables that can affect the assessment of the effectiveness of FMT in specific diseases. The risks associated with FMT and the threat of antimicrobial resistance for this therapeutic approach were reviewed. From gastrointestinal diseases to neurodevelopmental disorders, understanding the roles of the gut microbiota in health and disease should be at the heart of developing novel, standardized, yet personalized, methods for this ancient therapeutic approach.

A Comparative Pilot Study of Bacterial and Fungal Dysbiosis in Neurodevelopmental Disorders and Gastrointestinal Disorders: Commonalities, Specificities and Correlations with Lifestyle.

Gastrointestinal disorders (GIDs) are a common comorbidity in patients with neurodevelopmental disorders (NDDs), while anxiety-like behaviors are common among patients with gastrointestinal diseases. It is still unclear as to which microbes differentiate these two groups. This pilot study aims at proposing an answer by exploring both the bacteriome and the mycobiome in a cohort of 55 volunteers with NDD, GID or controls, while accounting for additional variables that are not commonly included such as probiotic intake and diet. Recruited participants answered a questionnaire and provided a stool sample using the Fisherbrand collection kit. Bacterial and fungal DNA was extracted using the Qiagen Stool minikit. Sequencing (16sRNA and ITS) and phylogenetic analyses were performed using the PE300 Illumina Miseq v3 sequencing. Statistical analysis was performed using the R package. Results showed a significant decrease in bacterial alpha diversity in both NDD and GID, but an increased fungal alpha diversity in NDD. Data pointed at a significant bacterial dysbiosis between the three groups, but the mycobiome dysbiosis is more pronounced in NDD than in GID. Fungi seem to be more affected by probiotics, diet and antibiotic exposure and are proposed to be the main key player in differentiation between NDD and GID dybiosis.

Epigenetic Effects of Gut Metabolites: Exploring the Path of Dietary Prevention of Type 1 Diabetes.

Type 1 diabetes (T1D) has increased over the past half century and has now become the second most frequent autoimmune disease in childhood and one of major public health concern worldwide. Evidence suggests that modern lifestyles and rapid environmental changes are driving factors that underlie this increase. The integration of these two factors brings about changes in food intake. This, in turn, alters epigenetic regulations of the genome and intestinal microbiota composition, which may ultimately play a role in pathogenesis of T1D. Recent evidence shows that dysbiosis of the gut microbiota is closely associated with T1D and that a dietary intervention can influence epigenetic changes associated with this disease and may modify gene expression patterns through epigenetic mechanisms. In this review focus on how a diet can shape the gut microbiome, its effect on the epigenome in T1D, and the future of T1D management by microbiome therapy.

Importance of Dietary Changes During the Coronavirus Pandemic: How to Upgrade Your Immune Response.

The new coronavirus pandemic continues to spread causing further public health, social, and economic issues. The disparities in the rates of death between countries poses questions about the importance of lifestyle habits and the immune status of populations. An exploration of dietary habits and COVID-19-related death might unravel associations between these two variables. Indeed, while both nutritional excess and deficiency are associated with immunodeficiency, adequate nutrition leading to an optimally functioning immune system may be associated with better outcomes with regards to preventing infection and complications of COVID-19, as well as developing a better immune response to other pathogenic viruses and microorganisms. This article outlines the key functions of the immune system and how macronutrients, micronutrients, and metabolites from the gut microbiome can be essential in the development of an efficient immune system. In addition, the effects of intermittent fasting on the inflammatory state as well as metabolic parameters will be discussed.

The Promising Role of Probiotics in Managing the Altered Gut in Autism Spectrum Disorders.

Gastrointestinal symptoms (GIS) have been reported repeatedly in people with autism spectrum disorder (ASD) and studies have reported interesting correlations between severity of behavioral and gastrointestinal symptoms. Growing evidence indicates that the gut microbiota in ASD is altered with various shifts described at different taxonomic levels, pointing to the importance of considering the gut-brain axis in treatment of these disorders. Probiotics are live beneficial bacteria that are ingested as food or customized pills. These beneficial bacteria, when added in sufficient amounts, can correct the dysbiosis. Because probiotics have shown success in treating irritable bowel syndrome (IBS), it is plausible to investigate whether they can induce alleviation of behavioral symptoms as well. Probiotics show, in some clinical studies, their potential benefits (1) in improving gastrointestinal dysfunction, (2) in correcting dysbiosis, (3) in consequently reducing the severity of ASD symptoms. This review compiles data from selected studies that investigate these benefits and the mechanisms that mediate these effects, which include the production of metabolites, hormones, and neurotransmitters and the regulation of pro-inflammatory and regulatory cytokines. Future research based on more randomized, controlled studies with a larger population size and standardized use of strains, concentration of probiotics, duration of treatments, and methods of DNA extraction is still needed in this area, which may lead to more robust results.

Targeting the gut microbiome: A brief report on the awareness, practice, and readiness to engage in clinical interventions in Qatar.

BACKGROUND: There has been a growing global interest in the role of gut microbiota in the pathogenesis of diseases and the potentials of targeting the microbiome in clinical interventions. Very few clinical studies in Qatar focused on gut microbiome. This study aimed to assess the awareness of healthcare professionals, scientists, and the general public on the role of gut microbiota in health and diseases and, more specifically, in disorders of the gut-brain axis such as neurodevelopmental disorders (NDDs) or gastrointestinal (GI) disorders. It also aimed to evaluate the readiness of the population to engage in clinical trials involving dietary interventions or fecal transplants. METHODS: A total of 156 participants were recruited to answer questionnaires-from healthcare professionals and scientists (HSs; n = 44) and the general public (n = 112). Participants from the general public self-reported their diagnosis of NDDs-autism or attention deficit hyperactivity disorder (n = 36)-or GI diseases or disorders (n = 18) or as having none of them (n = 58). Two questionnaires for HSs and for the general public were distributed, and basic descriptive and statistical analyses were conducted using the Fisher's exact test. RESULTS: Among the participating HSs, 95% admitted that they had minimum to no knowledge on the role of gut microbes in health and diseases, and only 15.9% felt that their peers were knowledgeable about it. Nevertheless, 97.7% of HSs thought that gut microbiota should be considered when devising treatment plans as 79.1% believed that gut dysbiosis is involved in the pathogenesis of diseases. For the general public, 54% stated that they have read about studies on the potential benefits of microbes in the prevention, treatment, and management of diseases, with a higher proportion of them belonging to the GI group (p = 0.0523). The GI group was also more aware of the existence of the use of fecal transplants for treating their condition (p = 0.01935). Awareness was also reflected in participants' attempts to engage in dietary changes, as 40% tried a dietary intervention, which has noticeably changed their or their child's symptoms. This study reported a highly significant association between being exposed to multiple antibiotic courses before three years of age and being part of the NDD group (p = 0.0003). Public readiness to engage in interventions that target the gut microbiome, such as intensive dietary interventions or even fecal transplants, was perceived by HSs to be lower than what was stated by the public, with 87.96% of public being ready to engage in intensive dietary interventions and 66.98% in fecal transplants. CONCLUSION: The study revealed that the role of gut microbes in health and diseases, and especially through the gut-brain axis, is still unclear in both the scientific community and general public. While acknowledging the importance of gut microbes, the lack of information regarding the link between lifestyle and gut microbes is considered to hold the public in the precontemplation/contemplation stages of the transtheoretical model of behavioral change. An interdisciplinary approach to new knowledge produced by microbiome studies is needed to run awareness campaigns and continue professional development activities on the benefits of lifestyle-based modulation of gut microbiome, thus engaging the general public in lifestyle changes and facilitating clinical research in human microbiome investigations in Qatar.

The role of gut microbiota in atopic asthma and allergy, implications in the understanding of disease pathogenesis.

Asthma is a clinical syndrome characterized by chronic airway inflammation. There is mounting evidence on the role of microbiota in the development of asthma. This review focuses on the role of microbiota in maintaining the integrity of the epithelia and their role in regulating the immune response. The review compiles data from multiple studies on the role of microbiota in the innate immune response and the development and differentiation of CD4+ T cells, a major component of the adaptive arm of the immune response. As a result of dysbiosis, invariant natural killer T cells may induce T helper 2 cell differentiation and immunoglobulin E isotype switching through the release of interleukin-4 and interleukin-13. Furthermore, degradation of immunoglobulin A antibodies, increased circulating mast cells and basophils, and inflammation are among other mechanisms by which dysbiosis can induce or exacerbate asthma. After explaining the underlying mechanisms, the review derives conclusions from studies that investigate dysbiosis in infancy and the development of asthma later in life. The review also includes studies that investigate asthmatic mothers and the development of asthma in children and the role of dysbiosis in that regard. Finally, the review explains the statistical relationship between eczema and asthma through multiple studies that investigate the role of dysbiosis in both atopic states. This review provides insight into the role of dysbiosis in asthma, and an understanding that is required to establish clinical trials which aim to modulate the gut microbiota as a means of preventing and treating asthma.

Adrenomedullin blockade induces regression of tumor neovessels through interference with vascular endothelial-cadherin signalling.

The cellular and molecular mechanisms by which adrenomedullin (AM) blockade suppresses tumor neovessels are not well defined. Herein, we show that AM blockade using anti-AM and anti-AM receptors antibodies targets vascular endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), and induces regression of unstable nascent tumor neovessels. The underlying mechanism involved, and shown in vitro and in vivo in mice, is the disruption of the molecular engagement of the endothelial cell-specific junctional molecules vascular endothelial-cadherin (VE-cadherin)/ß-catenin complex. AM blockade increases endothelial cell permeability by inhibiting cell-cell contacts predominantly through disruption of VE-cadherin/ß-catenin/Akt signalling pathway, thereby leading to vascular collapse and regression of tumor neovessels. At a molecular level, we show that AM blockade induces tyrosine phosphorylation of VE-cadherin at a critical tyrosine, Tyr731, which is sufficient to prevent the binding of ß-catenin to the cytoplasmic tail of VE-cadherin leading to the inhibition of cell barrier function. Furthermore, we demonstrate activation of Src kinase by phosphorylation on Tyr416, supporting a role of Src to phosphorylate Tyr731-VE-cadherin. In this model, Src inhibition impairs αAM and αAMR-induced Tyr731-VE-cadherin phosphorylation in a dose-dependent manner, indicating that Tyr731-VE-cadherin phosphorylation state is dependent on Src activation. We found that AM blockade induces ß-catenin phosphorylation on Ser33/Ser37/Thr41 sites in both ECs and VSMCs both in vitro and in vivo in mice. These data suggest that AM blockade selectively induces regression of unstable tumor neovessels, through disruption of VE-cadherin signalling. Targeting AM system may present a novel therapeutic target to selectively disrupt assembly and induce regression of nascent tumor neovessels, without affecting normal stabilized vasculature.