Feeding melancholic microbes: MyNewGut recommendations on diet and mood

Summary: Depression is a highly prevalent disorder which exerts a major economic impact in all European countries. The brain-gut-microbiota axis has been described as a new paradigm for advancing understanding and treatment of the disorder. There is now over-whelming evidence to support the fact that gut microbes have a major impact on central neurochemistry and behaviour, especially stress related disorders such as depression. Recent studies indicate that patients with depression have a gut dysbiosis. The reason for this dysbiosis is uncertain. Over recent decades, dietary patterns in Europe and elsewhere have undergone major compositional changes, with increased intakes of red meat, high fat foods, and refined sugars. Individuals who consume a Mediterranean diet have lower rates of depression and a recent study suggests that a Mediterranean diet may have antidepressant properties. Assuming this to be the case, which components of the Mediterranean diet mediate the effects? Highly levels of polyphenols or polyunsaturated fatty acids are obvious candidates. We in the MyNewGut consortium recommend that patients with depression or vulnerability to depression should be encouraged to enhance a plant-based diet with a high content of grains/fibres and fish

Two functional variants of IRF5 influence the development of macular edema in patients with non-anterior uveitis.

Objective Interferon (IFN) signaling plays a crucial role in autoimmunity. Genetic variation in interferon regulatory factor 5 (IRF5), a major regulator of the type I interferon induction, has been associated with risk of developing several autoimmune diseases. In the current study we aimed to evaluate whether three sets of correlated IRF5 genetic variants, independently associated with SLE and with different functional roles, are involved in uveitis susceptibility and its clinical subphenotypes. Methods Three IRF5 polymorphisms, rs2004640, rs2070197 and rs10954213, representative of each group, were genotyped using TaqMan® allelic discrimination assays in a total of 263 non-anterior uveitis patients and 724 healthy controls of Spanish origin. Results A clear association between two of the three analyzed genetic variants, rs2004640 and rs10954213, and the absence of macular edema was observed in the case/control analysis (PFDR=5.07E-03, OR=1.48, CI 95%=1.14-1.92 and PFDR=3.37E-03, OR=1.54, CI 95%=1.19-2.01, respectively). Consistently, the subphenotype analysis accordingly with the presence/absence of this clinical condition also reached statistical significance (rs2004640: P=0.037, OR=0.69, CI 95%=0.48-0.98; rs10954213: P=0.030, OR=0.67, CI 95%=0.47-0.96), thus suggesting that both IRF5 genetic variants are specifically associated with the lack of macular edema in uveitis patients. Conclusion Our results clearly showed for the first time that two functional genetic variants of IRF5 may play a role in the development of macular edema in non-anterior uveitis patients. Identifying genetic markers for macular edema could lead to the possibility of developing novel treatments or preventive therapies

The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids

Rationale: Evidence suggests that the gut microbiome is involved in the development of cardiovascular disease, with the host–microbe interaction regulating immune and metabolic pathways. However, there was no firm evidence for associations between microbiota and metabolic risk factors for cardiovascular disease from large-scale studies in humans. In particular, there was no strong evidence for association between cardiovascular disease and aberrant blood lipid levels. Objectives: To identify intestinal bacteria taxa, whose proportions correlate with body mass index and lipid levels, and to determine whether lipid variance can be explained by microbiota relative to age, sex, and host genetics. Methods and Results: We studied 893 subjects from the LifeLines-DEEP population cohort. After correcting for age and sex, we identified 34 bacterial taxa associated with body mass index and blood lipids; most are novel associations. Cross-validation analysis revealed that microbiota explain 4.5% of the variance in body mass index, 6% in triglycerides, and 4% in high-density lipoproteins, independent of age, sex, and genetic risk factors. A novel risk model, including the gut microbiome explained ≤25.9% of high-density lipoprotein variance, significantly outperforming the risk model without microbiome. Strikingly, the microbiome had little effect on low-density lipoproteins or total cholesterol. Conclusions: Our studies suggest that the gut microbiome may play an important role in the variation in body mass index and blood lipid levels, independent of age, sex, and host genetics. Our findings support the potential of therapies altering the gut microbiome to control body mass, triglycerides, and high-density lipoproteins

Intestinal Microbiota and Celiac Disease: Cause, Consequence or Co-Evolution?

It is widely recognized that the intestinal microbiota plays a role in the initiation and perpetuation of intestinal inflammation in numerous chronic conditions. Most studies report intestinal dysbiosis in celiac disease (CD) patients, untreated and treated with a gluten-free diet (GFD), compared to healthy controls. CD patients with gastrointestinal symptoms are also known to have a different microbiota compared to patients with dermatitis herpetiformis and controls, suggesting that the microbiota is involved in disease manifestation. Furthermore, a dysbiotic microbiota seems to be associated with persistent gastrointestinal symptoms in treated CD patients, suggesting its pathogenic implication in these particular cases. GFD per se influences gut microbiota composition, and thus constitutes an inevitable confounding factor in studies conducted in CD patients. To improve our understanding of whether intestinal dysbiosis is the cause or consequence of disease, prospective studies in healthy infants at family risk of CD are underway. These studies have revealed that the CD host genotype selects for the early colonizers of the infant’s gut, which together with environmental factors (e.g., breast-feeding, antibiotics, etc.) could influence the development of oral tolerance to gluten. Indeed, some CD genes and/or their altered expression play a role in bacterial colonization and sensing. In turn, intestinal dysbiosis could promote an abnormal response to gluten or other environmental CD-promoting factors (e.g., infections) in predisposed individuals. Here, we review the current knowledge of host-microbe interactions and how host genetics/epigenetics and environmental factors shape gut microbiota and may influence disease risk. We also summarize the current knowledge about the potential mechanisms of action of the intestinal microbiota and specific components that affect CD pathogenesis

Circadian Disruption and Mental Health: The Chronotherapeutic Potential of Microbiome-Based and Dietary Strategies

Mental illness is alarmingly on the rise, and circadian disruptions linked to a modern lifestyle may largely explain this trend. Impaired circadian rhythms are associated with mental disorders. The evening chronotype, which is linked to circadian misalignment, is a risk factor for severe psychiatric symptoms and psychiatric metabolic comorbidities. Resynchronization of circadian rhythms commonly improves psychiatric symptoms. Furthermore, evidence indicates that preventing circadian misalignment may help reduce the risk of psychiatric disorders and the impact of neuro–immuno–metabolic disturbances in psychiatry. The gut microbiota exhibits diurnal rhythmicity, as largely governed by meal timing, which regulates the host’s circadian rhythms. Temporal circadian regulation of feeding has emerged as a promising chronotherapeutic strategy to prevent and/or help with the treatment of mental illnesses, largely through the modulation of gut microbiota. Here, we provide an overview of the link between circadian disruption and mental illness. We summarize the connection between gut microbiota and circadian rhythms, supporting the idea that gut microbiota modulation may aid in preventing circadian misalignment and in the resynchronization of disrupted circadian rhythms. We describe diurnal microbiome rhythmicity and its related factors, highlighting the role of meal timing. Lastly, we emphasize the necessity and rationale for further research to develop effective and safe microbiome and dietary strategies based on chrononutrition to combat mental illness

Development and Psychometric Validation of the Breast Cancer Stigma Assessment Scale for Women with Breast Cancer and Its Survivors

Background: The increase in breast cancer cases and breast cancer survival makes it advisable to quantify the impact of the health-related stigma of this disease. Purpose/Objectives: To develop and validate a breast cancer stigma scale in Spanish. Methods: Women diagnosed with, or survivors of, breast cancer were included. The development of the Breast Cancer Stigma Assessment Scale (BCSAS) involved both a literature review and personal interviews. Content validity was assessed using a Delphi study and a pilot test; construct validity was evaluated using an exploratory factor analysis; and convergent validity was assessed using six scales. Cronbach’s α internal consistency and test-retest reliability were used to determine the reliability of the scales. Results: 231 women responded to the 28-item scale. The BCSAS showed good reliability, with α = 0.897. Seven factors emerged: concealment (α = 0.765), disturbance (α = 0.772), internalized stigma (α = 0.750), aesthetics (α = 0.779), course (α = 0.599), danger (α = 0.502), and origin (α = 0.350). The test-retest reliability was 0.830 (p < 0.001). Significant correlation was observed with event centrality (r = 0.701), anxiety–depression (r = 0.668), shame (r = 0.645), guilt (r = 0.524), and quality of life (r = −0.545). Conclusions: The BCSAS is a reliable and valid measure of stigma in women with breast cancer and its survivors. It could be useful for detecting stigma risk and establishing psychotherapeutic and care priorities

Manipulation of gut microbiota blunts the ventilatory response to hypercapnia in adult rats

Background: It is increasingly evident that perturbations to the diversity and composition of the gut microbiota have significant consequences for the regulation of integrative physiological systems. There is growing interest in the potential contribution of microbiota-gut-brain signalling to cardiorespiratory control in health and disease. Methods: In adult male rats, we sought to determine the cardiorespiratory effects of manipulation of the gut microbiota following a 4-week administration of a cocktail of antibiotics. We subsequently explored the effects of administration of faecal microbiota from pooled control (vehicle) rat faeces, given by gavage to vehicle- and antibiotic-treated rats. Findings: Antibiotic intervention depressed the ventilatory response to hypercapnic stress in conscious animals, owing to a reduction in the respiratory frequency response to carbon dioxide. Baseline frequency, respiratory timing variability, and the expression of apnoeas and sighs were normal. Microbiota-depleted rats had decreased systolic blood pressure. Faecal microbial transfer to vehicle- and antibiotic-treated animals also disrupted the gut microbiota composition, associated with depressed ventilatory responsiveness to hypercapnia. Chronic antibiotic intervention or faecal microbial transfer both caused significant disruptions to brainstem monoamine neurochemistry, with increased homovanillic acid:dopamine ratio indicative of increased dopamine turnover, which correlated with the abundance of several bacteria of six different phyla. Interpretation: Chronic antibiotic administration and faecal microbial transfer disrupt gut microbiota, brainstem monoamine concentrations and the ventilatory response to hypercapnia. We suggest that aberrant microbiota-gut-brain axis signalling has a modulatory influence on respiratory behaviour during hypercapnic stress. Fund: Department of Physiology and APC Microbiome Ireland, University College Cork, Ireland.This project was funded by the Department of Physiology, and the APC Microbiome Ireland (funded by Science Foundation Ireland (SFI/12/RC/2273)), University College Cork, Ireland