Akkermansia muciniphila in neuropsychiatric disorders: friend or foe?

An accumulating body of evidence suggests that the bacterium Akkermansia muciniphila exhibits positive systemic effects on host health, mainly by improving immunological and metabolic functions, and it is therefore regarded as a promising potential probiotic. Recent clinical and preclinical studies have shown that A. muciniphila plays a vital role in a variety of neuropsychiatric disorders by influencing the host brain through the microbiota-gut-brain axis (MGBA). Numerous studies observed that A. muciniphila and its metabolic substances can effectively improve the symptoms of neuropsychiatric disorders by restoring the gut microbiota, reestablishing the integrity of the gut mucosal barrier, regulating host immunity, and modulating gut and neuroinflammation. However, A. muciniphila was also reported to participate in the development of neuropsychiatric disorders by aggravating inflammation and influencing mucus production. Therefore, the exact mechanism of action of A. muciniphila remains much controversial. This review summarizes the proposed roles and mechanisms of A. muciniphila in various neurological and psychiatric disorders such as depression, anxiety, Parkinson's disease, Alzheimer's disease, multiple sclerosis, strokes, and autism spectrum disorders, and provides insights into the potential therapeutic application of A. muciniphila for the treatment of these conditions.

The Role of Psychobiotics in Supporting the Treatment of Disturbances in the Functioning of the Nervous System-A Systematic Review.

Stress and anxiety are common phenomena that contribute to many nervous system dysfunctions. More and more research has been focusing on the importance of the gut-brain axis in the course and treatment of many diseases, including nervous system disorders. This review aims to present current knowledge on the influence of psychobiotics on the gut-brain axis based on selected diseases, i.e., Alzheimer's disease, Parkinson's disease, depression, and autism spectrum disorders. Analyses of the available research results have shown that selected probiotic bacteria affect the gut-brain axis in healthy people and people with selected diseases. Furthermore, supplementation with probiotic bacteria can decrease depressive symptoms. There is no doubt that proper supplementation improves the well-being of patients. Therefore, it can be concluded that the intestinal microbiota play a relevant role in disorders of the nervous system. The microbiota-gut-brain axis may represent a new target in the prevention and treatment of neuropsychiatric disorders. However, this topic needs more research. Such research could help find effective treatments via the modulation of the intestinal microbiome.

BMI, Alcohol Consumption and Gut Microbiome Species Richness Are Related to Structural and Functional Neurological Abnormalities.

Background: The incidence of neurological diseases is increasing throughout the world. The aim of the present study was to identify nutrition and microbiome factors related to structural and functional neurological abnormalities to optimize future preventive strategies. Methods: Two hundred thirty-eight patients suffering from (1) structural (neurodegeneration) or (2) functional (epilepsy) neurological abnormalities or (3) chronic pain (migraine) and 612 healthy control subjects were analyzed by validated 12-month food frequency questionnaire (FFQ) and 16S rRNA microbiome sequencing (from stool samples). A binomial logistic regression model was applied for risk calculation and functional pathway analysis to show which functional pathway could discriminate cases and healthy controls. Results: Detailed analysis of more than 60 macro- and micronutrients revealed no distinct significant difference between cases and controls, whereas BMI, insulin resistance and metabolic inflammation in addition to alcohol consumption were major drivers of an overall neurological disease risk. The gut microbiome analysis showed decreased alpha diversity (Shannon index: p = 9.1× 10-7) and species richness (p = 1.2 × 10-8) in the case group as well as significant differences in beta diversity between cases and controls (Bray-Curtis: p = 9.99 × 10-4; Jaccard: p = 9.99 × 10-4). The Shannon index showed a beneficial effect (OR = 0.59 (95%-CI (0.40, 0.87); p = 8 × 10-3). Cases were clearly discriminated from healthy controls by environmental information processing, signal transduction, two component system and membrane transport as significantly different functional pathways. Conclusions: In conclusion, our data indicate that an overall healthy lifestyle, in contrast to supplementation of single micro- or macronutrients, is most likely to reduce overall neurological abnormality risk and that the gut microbiome is an interesting target to develop novel preventive strategies.

COVID-19 associated rhino-orbital-cerebral mucormycosis: An observational study from Eastern India, with special emphasis on neurological spectrum.

AIMS: 1: Describe the epidemiology and determine risk factors for COVID-19 associated mucormycosis. 2: Elaborate the clinical spectrum of Rhino-Orbital-Cerebral Mucormycosis (ROCM), pattern of neuroaxis involvement and it's radiological correlates. METHODS: Observational study. Consecutive, confirmed cases of mucormycosis (N = 55) were included. A case of mucormycosis was defined as one who had clinical and radiological features consistent with mucormycosis along with demonstration of the fungus in tissue via KOH mount/culture/histopathological examination (HPE). Data pertaining to epidemiology, risk factors, clinico-radiological features were analysed using percentage of total cases. RESULTS: Middle aged, diabetic males with recent COVID-19 infection were most affected. New onset upper jaw toothache was a striking observation in several cases. Among neurological manifestations headache, proptosis, vision loss, extraocular movement restriction; cavernous sinus, meningeal and parenchymal involvement were common. Stroke in ROCM followed a definitive pattern with watershed infarction. CONCLUSIONS: New onset upper jaw toothache and loosening of teeth should prompt an immediate search for mucormycosis in backdrop of diabetic patients with recent COVID-19 disease, aiding earlier diagnosis and treatment initiation. Neuroaxis involvement was characterized by a multitude of features pertaining to involvement of optic nerve, extraocular muscles, meninges, brain parenchyma and internal carotid artery.

Helicobacter pylori Infection and Extragastric Diseases-A Focus on the Central Nervous System.

Helicobacter pylori (H. pylori) is most known to cause a wide spectrum of gastrointestinal impairments; however, an increasing number of studies indicates that H. pylori infection might be involved in numerous extragastric diseases such as neurological, dermatological, hematologic, ocular, cardiovascular, metabolic, hepatobiliary, or even allergic diseases. In this review, we focused on the nervous system and aimed to summarize the findings regarding H. pylori infection and its involvement in the induction/progression of neurological disorders. Neurological impairments induced by H. pylori infection are primarily due to impairments in the gut-brain axis (GBA) and to an altered gut microbiota facilitated by H. pylori colonization. Currently, regarding a potential relationship between Helicobacter infection and neurological disorders, most of the studies are mainly focused on H. pylori.

The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders.

Emerging evidence indicates that the gut microbiota play a crucial role in the bidirectional communication between the gut and the brain suggesting that the gut microbes may shape neural development, modulate neurotransmission and affect behavior, and thereby contribute to the pathogenesis and/or progression of many neurodevelopmental, neuropsychiatric, and neurological conditions. This review summarizes recent data on the role of microbiota-gut-brain axis in the pathophysiology of neuropsychiatric and neurological disorders including depression, anxiety, schizophrenia, autism spectrum disorders, Parkinson's disease, migraine, and epilepsy. Also, the involvement of microbiota in gut disorders co-existing with neuropsychiatric conditions is highlighted. We discuss data from both in vivo preclinical experiments and clinical reports including: (1) studies in germ-free animals, (2) studies exploring the gut microbiota composition in animal models of diseases or in humans, (3) studies evaluating the effects of probiotic, prebiotic or antibiotic treatment as well as (4) the effects of fecal microbiota transplantation.

Modulating host gene expression via gut microbiome-microRNA interplay to treat human diseases.

The human gastrointestinal (GI) tract hosts trillions of microbial inhabitants involved in maintaining intestinal homeostasis, dysbiosis of which provokes a motley of pathogenic and autoimmune disorders. While the mechanisms by which the microbiota modulates human health are manifold, their liberated metabolites from ingested dietary supplements play a crucial role by bidirectionally regulating the expression of micro-ribonucleic acids (miRNAs). miRNAs are small endogenous non-coding RNAs (ncRNAs) that have been confirmed to be involved in an interplay with microbiota to regulate host gene expression. This comprehensive review focuses on key principles of miRNAs, their regulation, and crosstalk with gut microbiota to influence host gene expression in various human disorders, by bringing together important recent findings centric around miRNA-microbiota interactions in diseases along various axis of the gut with other organs. We also attempt to lay emphasis on exploiting the avenues of gut-directed miRNA therapeutics using rudimentary dietary supplements to regulate abnormal host gene expression in diseases, opening doors to an accessible and economical therapeutic strategy.

Role of microbiota-derived short-chain fatty acids in nervous system disorders.

During the past decade, accumulating evidence from the research highlights the suggested effects of bacterial communities of the human gut microbiota and their metabolites on health and disease. In this regard, microbiota-derived metabolites and their receptors, beyond the immune system, maintain metabolism homeostasis, which is essential to maintain the host's health by balancing the utilization and intake of nutrients. It has been shown that gut bacterial dysbiosis can cause pathology and altered bacterial metabolites' formation, resulting in dysregulation of the immune system and metabolism. The short-chain fatty acids (SCFAs), such as butyrate, acetate, and succinate, are produced due to the fermentation process of bacteria in the gut. It has been noted remodeling in the gut microbiota metabolites associated with the pathophysiology of several neurological disorders, such as Alzheimer's disease, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, stress, anxiety, depression, autism, vascular dementia, schizophrenia, stroke, and neuromyelitis optica spectrum disorders, among others. This review will discuss the current evidence from the most significant studies dealing with some SCFAs from gut microbial metabolism with selected neurological disorders.

Neurological Complications of COVID-19 in Children.

Neurological complications of coronavirus disease 2019 (COVID-19) are highly variable and can be quite severe, but they are rare in children. A careful understanding of the variety of presentations of neurological symptoms related to COVID-19 is critical for the effective management of these patients. Given the smaller numbers of children with these complications, a comprehensive review of neurological presentations in adults with COVID-19 may help facilitate the understanding of those complications that may present in children and how these presentations may be similar. [Pediatr Ann. 2021;50(6):e259-e263.].

Marine Natural Products: Promising Candidates in the Modulation of Gut-Brain Axis towards Neuroprotection.

In recent decades, several neuroprotective agents have been provided in combating neuronal dysfunctions; however, no effective treatment has been found towards the complete eradication of neurodegenerative diseases. From the pathophysiological point of view, growing studies are indicating a bidirectional relationship between gut and brain termed gut-brain axis in the context of health/disease. Revealing the gut-brain axis has survived new hopes in the prevention, management, and treatment of neurodegenerative diseases. Accordingly, introducing novel alternative therapies in regulating the gut-brain axis seems to be an emerging concept to pave the road in fighting neurodegenerative diseases. Growing studies have developed marine-derived natural products as hopeful candidates in a simultaneous targeting of gut-brain dysregulated mediators towards neuroprotection. Of marine natural products, carotenoids (e.g., fucoxanthin, and astaxanthin), phytosterols (e.g., fucosterol), polysaccharides (e.g., fucoidan, chitosan, alginate, and laminarin), macrolactins (e.g., macrolactin A), diterpenes (e.g., lobocrasol, excavatolide B, and crassumol E) and sesquiterpenes (e.g., zonarol) have shown to be promising candidates in modulating gut-brain axis. The aforementioned marine natural products are potential regulators of inflammatory, apoptotic, and oxidative stress mediators towards a bidirectional regulation of the gut-brain axis. The present study aims at describing the gut-brain axis, the importance of gut microbiota in neurological diseases, as well as the modulatory role of marine natural products towards neuroprotection.

Protocol for a systematic review on the role of the gut microbiome in paediatric neurological disorders.

INTRODUCTION: The gut-brain axis refers to the bidirectional communication that occurs between the intestinal tract and central nervous system (CNS). Through a series of neural, immune, endocrine, and metabolic signalling pathways, commensal microbiota are able to influence CNS development and neurological function. Alterations in gut microbiota have been implicated in various neuropathologies. The purpose of this review is to evaluate and summarise existing literature assessing the role of specific bacterial taxa on the development of neurodevelopmental, neuropsychiatric, and neurodegenerative pathologies of childhood. We will also discuss microbiota-based therapies dietary interventions and their efficacy. METHODS AND ANALYSIS: We will search PubMed, Cochrane Library, and OVID electronic databases for articles published between January 1980 and February 2021. A search method involving two rounds of reviewing the literature using a three-step method in each round will be performed. Two researchers will be selected, and screen titles and abstracts independently. The full text of selected articles will be assessed against inclusion criteria. Data will be extracted and evaluated using the appropriate Critical Appraisal Skills Programme (CASP) checklist. ETHICS AND DISSEMINATION: Findings from this study will be shared across relevant paediatric neurology and gastroenterology societies and submitted for peer review. This study did not require institutional ethics approval.

Molecular Mechanisms Underlying the Beneficial Effects of Exercise on Brain Function and Neurological Disorders.

As life expectancy has increased, particularly in developed countries, due to medical advances and increased prosperity, age-related neurological diseases and mental health disorders have become more prevalent health issues, reducing the well-being and quality of life of sufferers and their families. In recent decades, due to reduced work-related levels of physical activity, and key research insights, prescribing adequate exercise has become an innovative strategy to prevent or delay the onset of these pathologies and has been demonstrated to have therapeutic benefits when used as a sole or combination treatment. Recent evidence suggests that the beneficial effects of exercise on the brain are related to several underlying mechanisms related to muscle-brain, liver-brain and gut-brain crosstalk. Therefore, this review aims to summarize the most relevant current knowledge of the impact of exercise on mood disorders and neurodegenerative diseases, and to highlight the established and potential underlying mechanisms involved in exercise-brain communication and their benefits for physiology and brain function.

Approaching precision medicine by tailoring the microbiota.

Accumulating evidence has revealed the link between the microbiota and various human diseases. Advances in high-throughput sequencing technologies have identified some consistent disease-associated microbial features, leading to the emerging concept of microbiome-based therapeutics. However, it is also becoming clear that there are considerable variations in the microbiota among patients with the same disease. Variations in the microbial composition and function contribute to substantial differences in metabolic status of the host via production of a myriad of biochemically and functionally different microbial metabolites. Indeed, compelling evidence indicates that individuality of the microbiome may result in individualized responses to microbiome-based therapeutics and other interventions. Mechanistic understanding of the role of the microbiota in diseases and drug metabolism would help us to identify causal relationships and thus guide the development of microbiome-based precision or personalized medicine. In this review, we provide an overview of current efforts to use microbiome-based interventions for the treatment of diseases such as cancer, neurological disorders, and diabetes to approach precision medicine.

Gut-Brain Axis: Role of Gut Microbiota on Neurological Disorders and How Probiotics/Prebiotics Beneficially Modulate Microbial and Immune Pathways to Improve Brain Functions.

The gut microbiome acts as an integral part of the gastrointestinal tract (GIT) that has the largest and vulnerable surface with desirable features to observe foods, nutrients, and environmental factors, as well as to differentiate commensals, invading pathogens, and others. It is well-known that the gut has a strong connection with the central nervous system (CNS) in the context of health and disease. A healthy gut with diverse microbes is vital for normal brain functions and emotional behaviors. In addition, the CNS controls most aspects of the GI physiology. The molecular interaction between the gut/microbiome and CNS is complex and bidirectional, ensuring the maintenance of gut homeostasis and proper digestion. Besides this, several mechanisms have been proposed, including endocrine, neuronal, toll-like receptor, and metabolites-dependent pathways. Changes in the bidirectional relationship between the GIT and CNS are linked with the pathogenesis of gastrointestinal and neurological disorders; therefore, the microbiota/gut-and-brain axis is an emerging and widely accepted concept. In this review, we summarize the recent findings supporting the role of the gut microbiota and immune system on the maintenance of brain functions and the development of neurological disorders. In addition, we highlight the recent advances in improving of neurological diseases by probiotics/prebiotics/synbiotics and fecal microbiota transplantation via the concept of the gut-brain axis.

Cerebrospinal fluid oligoclonal bands in Neuroborreliosis are specific for Borrelia burgdorferi.

BACKGROUND: Cerebrospinal fluid (CSF) oligoclonal bands (OCB) occur in chronic or post-acute phase of inflammatory diseases of the central nervous system. OBJECTIVE: To determine whether CSF OCB in patients with neuroborreliosis (NB) are specific for borrelia burgdorferi senso lato. METHODS: We performed isoelectric focusing followed by immunoblotting in CSF of 10 NB patients and 11 controls (7 patients with multiple sclerosis, 2 patients with neuromyelitis optica spectrum disease, 1 patient with dementia and 1 patient with monoclonal gammopathy). Immunoblotting was performed using an uncoated as well as a borrelia antigen pre-coated nitrocellulose membrane (NCM). OCB were counted by visual inspection and photometric analysis. OCB were compared between uncoated und pre-coated NCM both in the NB and control group. For validation purposes inter-assay precision was determined by calculating the coefficient of variation (CV). RESULTS: Borrelia-specific OCB were found in the CSF of 9 NB patients and in none of the control subjects resulting in a sensitivity of 90% and a specificity of 100%. Number of NB specific OCB were 11±7 bands by photometric analyses compared to 9±5 bands by visual inspection. Validation experiments revealed an inconsistent inter-assay precision between visual and photometric analyses (NB uncoated: visual 28% versus photometric 14%, control subject uncoated: visual 16% versus photometric 24%). CONCLUSIONS: In CSF samples with positive OCB, Borrelia-specific bands were detected in almost all NB patients and in none of the control subjects. Inconsistent inter-assay precision may be explained by a poor comparability of visual and photometric approach.

Fecal microbiota transplantation in gastrointestinal and extraintestinal disorders.

Fecal microbiota transplantation (FMT) is the infusion of feces from a healthy donor into the gut of a recipient to treat a dysbiosis-related disease. FMT has been proven to be a safe and effective treatment for Clostridioides difficile infection, but increasing evidence supports the role of FMT in other gastrointestinal and extraintestinal diseases. The aim of this review is to paint the landscape of current evidence of FMT in different fields of application (including irritable bowel syndrome, inflammatory bowel disease, liver disorders, decolonization of multidrug-resistant bacteria, metabolic disorders and neurological disorders), as well as to discuss the current regulatory scenario of FMT, and hypothesize future directions of FMT.

Gut dysbiosis and age-related neurological diseases; an innovative approach for therapeutic interventions.

The gut microbiota is a complex ecosystem of bacteria, fungi, and viruses that acts as a critical regulator in microbial, metabolic, and immune responses in the host organism. Imbalances in the gut microbiota, termed "dysbiosis," often induce aberrant immune responses, which in turn disrupt the local and systemic homeostasis of the host. Emerging evidence has highlighted the importance of gut microbiota in intestinal diseases, and more recently, in age-related central nervous systems diseases, for example, stroke and Alzheimer's disease. It is now generally recognized that gut microbiota significantly influences host behaviors and modulates the interaction between microbiota, gut, and brain, via the "microbiota-gut-brain axis." Several approaches have been utilized to reduce age-related dysbiosis in experimental models and in clinical studies. These include strategies to manipulate the microbiome via fecal microbiota transplantation, administration of prebiotics and probiotics, and dietary interventions. In this review, we explore both clinical and preclinical therapies for treating age-related dysbiosis.

Enduring Behavioral Effects Induced by Birth by Caesarean Section in the Mouse.

Birth by Caesarean (C)-section impacts early gut microbiota colonization and is associated with an increased risk of developing immune and metabolic disorders. Moreover, alterations of the microbiome have been shown to affect neurodevelopmental trajectories. However, the long-term effects of C-section on neurobehavioral processes remain unknown. Here, we demonstrated that birth by C-section results in marked but transient changes in microbiome composition in the mouse, in particular, the abundance of Bifidobacterium spp. was depleted in early life. Mice born by C-section had enduring social, cognitive, and anxiety deficits in early life and adulthood. Interestingly, we found that these specific behavioral alterations induced by the mode of birth were also partially corrected by co-housing with vaginally born mice. Finally, we showed that supplementation from birth with a Bifidobacterium breve strain, or with a dietary prebiotic mixture that stimulates the growth of bifidobacteria, reverses selective behavioral alterations in C-section mice. Taken together, our data link the gut microbiota to behavioral alterations in C-section-born mice and suggest the possibility of developing adjunctive microbiota-targeted therapies that may help to avert long-term negative consequences on behavior associated with C-section birth mode.