Probiotics and the microbiota-gut-brain axis: focus on psychiatry

Purpose of Review Probiotics are living bacteria, which when ingested in adequate amounts, confer health benefits. Gutmicrobes are suggested to play a role in many psychiatric disorders and could be a potential therapeutic target. Between the gut and the brain, there is a bi-directional communication pathway called the microbiota-gut-brain axis. The purpose of this review is to examine data from recent interventional studies focusing on probiotics and the gut-brain axis for the treatment of depression, anxiety and schizophrenia.Recent Findings Probiotics are likely to improve depression but not schizophrenia. Regarding anxiety, there is only one trial which showed an effect of a multispecies probiotic. However, determinants like the duration of treatment, dosage and interactions have not been thoroughly investigated and deserve more scientific attention.Summary Microbiome-based therapies such as probiotics could be cautiously recommended for depression to enhance beneficial bacteria in the gut and to improve mood through the gut-brain axis

Psychometric properties of the Opening Minds Stigma Scale for Health Care Providers in 32 European countries – A bifactor ESEM representation

AimsTo measure the stigma of healthcare providers toward people suffering from mental illness, the Opening Minds Stigma Scale for Health Care Providers (OMS-HC) is a commonly applied instrument. However, this scale has not been thoroughly validated in many European countries, its psychometric properties are still unknown and data on practicing psychiatrists is lacking. Therefore, this multicenter study aimed to assess the psychometric characteristics of the 15-item OMS-HC in trainees and specialists in adult and child psychiatry in 32 countries across Europe.Materials and methodsThe OMS-HC was conducted as an anonymous online survey and sent via Email to European adult and child psychiatrists. Parallel analysis was used to estimate the number of OMS-HC dimensions. Separate for each country, the bifactor ESEM, a bifactor exploratory structural equation modeling approach, was applied to investigate the factor structure of the scale. Cross-cultural validation was done based on multigroup confirmatory factor analyses and reliability measures.ResultsA total of 4,245 practitioners were included, 2,826 (67%) female, 1,389 (33%) male. The majority (66%) of participants were specialists, with 78% working in adult psychiatry. When country data were analyzed separately, the bifactor model (higher-order factor solution with a general factor and three specific factors) showed the best model fit (for the total sample χ2/df = 9.760, RMSEA = 0.045 (0.042–0.049), CFI = 0.981; TLI = 0.960, WRMR = 1.200). The average proportion of variance explained by the general factor was high (ECV = 0.682). This suggests that the aspects of ‘attitude,’ ‘disclosure and help-seeking,’ and ‘social distance’ could be treated as a single dimension of stigma. Among the specific factors, the ‘disclosure and help-seeking’ factor explained a considerable unique proportion of variance in the observed scores.ConclusionThis international study has led to cross-cultural analysis of the OMS-HC on a large sample of practicing psychiatrists. The bifactor structure displayed the best overall model fit in each country. Rather than using the subscales, we recommend the total score to quantify the overall stigmatizing attitudes. Further studies are required to strengthen our findings in countries where the proposed model was found to be weak

Nutritional psychiatry in the treatment of psychotic disorders: Current hypotheses and research challenges

Current treatment for schizophrenia-spectrum disorders focusses primarily on psychotropic medication to treat symptoms, though their efficacy varies between patients and psychotropic medication is often accompanied by severe side effects. Nutritional interventions to prevent and treat mental illness have received considerable attention over recent years. However, evidence for nutritional interventions in schizophrenia-spectrum disorders remains limited in quantity and quality. Pathways currently in focus include: i) nutritional deficits and impairments in glucose metabolism, ii) inflammation and immune dysregulation (also known from the mild encephalitis hypothesis), and iii) altered gut microbiota. All of which appear to be interconnected. Key limiting factors for advancing research in this field are research challenges associated with assessing and interpreting inflammatory profiles, microbiota and subjective nutritional assessments, which is further complicated by illness characteristics. This review describes the state of evidence for key hypotheses, including underlying mechanisms, implicated in schizophrenia-spectrum disorders, the challenges in nutritional psychiatry research and the current state of nutrition interventions in mental healthcare

Gut-brain-crosstalk- the vagus nerve and the microbiota-gut-brain axis in depression. A narrative review

This narrative review summarizes key aspects of vagus nerve function as a main player in the microbiota-gut-brain axis in depression. Gut microbes as well as their metabolites signal directly to the vagus nerve via specialized enteroendocrine cells called “neuropods”. Some gut microbes, such as Lactobacillus rhamnosus, do not exhibit anti-anxiety effects in animal models when the vagus nerve is cut. Furthermore, vagus nerve function correlates with gut microbiota diversity, and short-chain fatty acid producers, such as Lactobacillales and Ruminococcaceae, are more abundant in individuals with better vagus function. The vagus nerve is activated by several neurotransmitters produced by the gut microbiota and regulates a cholinergic anti-inflammatory pathway (CAIP), which attenuates inflammation and decreases intestinal permeability, which may be relevant in the inflammatory subtype of depression. Psychobiotics, pre-, pro and synbiotics, with effects on behavior, work via the vagus nerve, and could be used to enhance its function. More research on gut microbiome interactions with the vagus nerve is necessary to develop targeted psychobiotics to improve vagus nerve function for optimal mental health

Thinking beyond Vaccination: Promising Add-On Strategies to Active Immunization and Vaccination in Pandemics—A Mini-Review

There is little doubt that final victories over pandemics, such as COVID-19, are attributed to herd immunity, either through post-disease convalescence or active immunization of a high percentage of the world’s population with vaccines, which demonstrate protection from infection and transmission and are available in large quantities at reasonable prices. However, it is assumable that humans with immune defects or immune suppression, e.g., as a consequence of allograft transplantation, cannot be immunized actively nor produce sufficient immune responses to prevent SARS-CoV-2 infections. These subjects desperately need other strategies, such as sophisticated protection measures and passive immunization. Hypertonic salt solutions attack vulnerable core areas of viruses; i.e., salt denatures surface proteins and thus prohibits virus penetration of somatic cells. It has to be ensured that somatic proteins are not affected by denaturation regarding this unspecific virus protection. Impregnating filtering facepieces with hypertonic salt solutions is a straightforward way to inactivate viruses and other potential pathogens. As a result of the contact of salt crystals on the filtering facepiece, these pathogens become denatured and inactivated almost quantitatively. Such a strategy could be easily applied to fight against the COVID-19 pandemic and other ones that may occur in the future. Another possible tool to fight the COVID-19 pandemic is passive immunization with antibodies against SARS-CoV-2, preferably from human origin. Such antibodies can be harvested from human patients’ sera who have successfully survived their SARS-CoV-2 infection. The disadvantage of a rapid decrease in the immunoglobulin titer after the infection ends can be overcome by immortalizing antibody-producing B cells via fusion with, e.g., mouse myeloma cells. The resulting monoclonal antibodies are then of human origin and available in, at least theoretically, unlimited amounts. Finally, dry blood spots are a valuable tool for surveilling a population’s immunity. The add-on strategies were selected as examples for immediate, medium and long-term assistance and therefore did not raise any claim to completeness

Fundamentally altered global- and microstate EEG characteristics in Huntington’s disease

Objective: Huntington’s disease (HD) is characterized by psychiatric, cognitive, and motor disturbances. The study aimed to determine electroencephalography (EEG) global state and microstate changes in HD and their relationship with cognitive and behavioral impairments. Methods: EEGs from 20 unmedicated HD patients and 20 controls were compared using global state properties (connectivity and dimensionality) and microstate properties (EEG microstate analysis). For four microstate classes (A, B, C, D), three parameters were computed: duration, occurrence, coverage. Global- and microstate properties were compared between groups and correlated with cognitive test scores for patients. Results: Global state analysis showed reduced connectivity in HD and an increasing dimensionality with increasing HD severity. Microstate analysis revealed parameter increases for classes A and B (coverage), decreases for C (occurrence) and D (coverage and occurrence). Disease severity and poorer test performances correlated with parameter increases for class A (coverage and occurrence), decreases for C (coverage and duration) and a dimensionality increase. Conclusions: Global state changes may reflect higher functional dissociation between brain areas and the complex microstate changes possibly the widespread neuronal death and corresponding functional deficits in brain regions associated with HD symptomatology. Significance: Combining global- and microstate analyses can be useful for a better understanding of progressive brain deterioration in HD

Probiotic, prebiotic, synbiotic and fermented food supplementation in psychiatric disorders: A systematic review of clinical trials

The use of probiotics, prebiotics, synbiotics or fermented foods can modulate the gut-brain axis and constitute a potentially therapeutic intervention in psychiatric disorders. This systematic review aims to identify current evidence regarding these interventions in the treatment of patients with DSM/ICD psychiatric diagnoses. Forty-seven articles from 42 studies met the inclusion criteria. Risk of bias was assessed in all included studies. Major depression was the most studied disorder (n = 19 studies). Studies frequently focused on schizophrenia (n = 11) and bipolar disorder (n = 5) and there were limited studies in anorexia nervosa (n = 4), ADHD (n = 3), Tourette (n = 1), insomnia (n = 1), PTSD (n = 1) and generalized anxiety disorder (n = 1). Except in MDD, current evidence does not clarify the role of probiotics and prebiotics in the treatment of mental illness. Several studies point to an improvement in the immune and inflammatory profile (e.g. CRP, IL6), which may be a relevant mechanism of action of the therapeutic response identified in these studies. Future research should consider lifestyle and dietary habits of patients as possible confounders that may influence inter-individual treatment response

Reduced Brain Electric Activity and Functional Connectivity in Bipolar Euthymia: An sLORETA Source Localization Study

Bipolar disorder (BD) is a chronic illness with a relapsing and remitting time course. Relapses are manic or depressive in nature and intermitted by euthymic states. During euthymic states, patients lack the criteria for a manic or depressive diagnosis, but still suffer from impaired cognitive functioning as indicated by difficulties in executive and language-related processing. The present study investigated whether these deficits are reflected by altered intracortical activity in or functional connectivity between brain regions involved in these processes such as the prefrontal and the temporal cortices. Vigilance-controlled resting state EEG of 13 euthymic BD patients and 13 healthy age- and sex-matched controls was analyzed. Head-surface EEG was recomputed into intracortical current density values in 8 frequency bands using standardized low-resolution electromagnetic tomography. Intracortical current densities were averaged in 19 evenly distributed regions of interest (ROIs). Lagged coherences were computed between each pair of ROIs. Source activity and coherence measures between patients and controls were compared (paired t tests). Reductions in temporal cortex activity and in large-scale functional connectivity in patients compared to controls were observed. Activity reductions affected all 8 EEG frequency bands. Functional connectivity reductions affected the delta, theta, alpha-2, beta-2, and gamma band and involved but were not limited to prefrontal and temporal ROIs. The findings show reduced activation of the temporal cortex and reduced coordination between many brain regions in BD euthymia. These activation and connectivity changes may disturb the continuous frontotemporal information flow required for executive and language-related processing, which is impaired in euthymic BD patients

Obesity Affects HDL Metabolism, Composition and Subclass Distribution

Background: Obesity increases the risk of coronary heart disease, partly due to its strong association with atherogenic dyslipidemia, characterized by high triglycerides and low high-density lipoprotein (HDL) cholesterol levels. Functional impairment of HDL may contribute to the increased cardiovascular mortality, but the effect of obesity on composition, structure, and function of HDL is not well understood. Design and Methods: We determined HDL composition, HDL subclass distribution, parameters of HDL function, and activities of most important enzymes involved in lipoprotein remodeling, including lecithin–cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in relatively young normal weight (n = 26), overweight (n = 22), and obese (n = 20) women. Results: Obesity (body mass index (BMI) ≥ 30) was associated with noticeable changes in LCAT and CETP activities and altered HDL composition, such as decreased apolipoprotein A-I, cholesterol, and phospholipid content, while pro-inflammatory HDL serum amyloid a content was increased. We observed a marked shift towards smaller HDL subclasses in obesity linked to lower anti-oxidative capacity of serum. LCAT activity, HDL subclass distribution, and HDL-cholesterol were associated with soluble leptin receptor, adiponectin, and liver enzyme activities. Of note, most of these alterations were only seen in obese women but not in overweight women. Conclusions: Obesity markedly affects HDL metabolism, composition, and subclass distribution linked to changes in liver and adipose tissue. HDL dysfunction may contribute to increased cardiovascular risk in obesity