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Brain-related comorbidities are frequently observed in chronic obstructive pulmonary disease (COPD) and are related to increased disease progression and mortality. To date, it is unclear which mechanisms are involved in the development of brain-related problems in COPD. In this study, a cigarette smoke and lipopolysaccharide (LPS) exposure murine model was used to induce COPD-like features and assess the impact on brain and behavior. Mice were daily exposed to cigarette smoke for 72 days, except for days 42, 52, and 62, on which mice were intratracheally exposed to the bacterial trigger LPS. Emphysema and pulmonary inflammation as well as behavior and brain pathology were assessed. Cigarette smoke-exposed mice showed increased alveolar enlargement and numbers of macrophages and neutrophils in bronchoalveolar lavage. Cigarette smoke exposure resulted in lower body weight, which was accompanied by lower serum leptin levels, more time spent in the inner zone of the open field, and decreased claudin-5 and occludin protein expression levels in brain microvessels. Combined cigarette smoke and LPS exposure resulted in increased locomotion and elevated microglial activation in the hippocampus of the brain. These novel findings show that systemic inflammation observed after combined cigarette smoke and LPS exposure in this COPD model is associated with increased exploratory behavior. Findings suggest that neuroinflammation is present in the brain area involved in cognitive functioning and that blood-brain barrier integrity is compromised. These findings can contribute to our knowledge about possible processes involved in brain-related comorbidities in COPD, which is valuable for optimizing and developing therapy strategies.

Background: Uncontrolled asthma can lead to severe exacerbations and reduced quality of life. Research has shown that the microbiome may be linked with asthma characteristics; however, its association with asthma control has not been explored. We aimed to investigate whether the gastrointestinal microbiome can be used to discriminate between uncontrolled and controlled asthma in children. Methods: 143 and 103 feces samples were obtained from 143 children with moderate-to-severe asthma aged 6 to 17 years from the SysPharmPediA study. Patients were classified as controlled or uncontrolled asthmatics, and their microbiome at species level was compared using global (alpha/beta) diversity, conventional differential abundance analysis (DAA, analysis of compositions of microbiomes with bias correction), and machine learning [Recursive Ensemble Feature Selection (REFS)]. Results: Global diversity and DAA did not find significant differences between controlled and uncontrolled pediatric asthmatics. REFS detected a set of taxa, including Haemophilus and Veillonella, differentiating uncontrolled and controlled asthma with an average classification accuracy of 81% (saliva) and 86% (feces). These taxa showed enrichment in taxa previously associated with inflammatory diseases for both sampling compartments, and with COPD for the saliva samples. Conclusion: Controlled and uncontrolled children with asthma can be differentiated based on their gastrointestinal microbiome using machine learning, specifically REFS. Our results show an association between asthma control and the gastrointestinal microbiome. This suggests that the gastrointestinal microbiome may be a potential biomarker for treatment responsiveness and thereby help to improve asthma control in children.

Reduced immune fitness can have a significant negative impact on work performance. The aim of the current study was to evaluate the impact of reduced immune fitness on job performance and associated costs for the Dutch economy. Data from n = 425 Dutch working adults (18–65 years old) who completed an online survey were analyzed to evaluate the number of days of absenteeism (not going to work) and presenteeism (working while sick) due to reduced immune fitness, and the performance level on days worked with reduced immune fitness. Data from for the year 2019 were analyzed. Participants reported 2.9 absenteeism days and 19 presenteeism days, with an average performance reduction of 22.8% when working on days with reduced immune fitness. Significantly more days of absenteeism and presenteeism were reported by women, individuals with a poorer immune fitness, and those with underlying disease. Performance impairment on days worked while experiencing reduced immune fitness was significantly greater among individuals with a younger age at the junior career level, those with underlying disease, and among highly educated individuals. The associated costs of reduced immune fitness were estimated at €4.3 billion for absenteeism and €6.4 billion for presenteeism. Together, the costs of reduced immune fitness for the Dutch economy in 2019 were estimated at €10.7 billion. These findings demonstrate that reduced immune fitness has a significant negative impact on the Dutch economy.

Human milk oligosaccharides (HMOs) and its most abundant component, 2’-Fucosyllactose (2’-FL), are known to be immunomodulatory. Previously, it was shown that HMOs and 2’-FL bind to the C-type lectin receptor DC-SIGN. Here we show, using a ligand-receptor competition assay, that a whole mixture of HMOs from pooled human milk (HMOS) and 2’-FL inhibit the binding of the carbohydrate-binding receptor DC-SIGN to its prototypical ligands, fucose and the oligosaccharide Lewis-B, (Leb) in a dose-dependent way. Interestingly, such inhibition by HMOS and 2’-FL was not detected for another C-type lectin, Langerin, evolutionary similar to DC-SIGN. The cell-ligand competition assay using DC-SIGN expressing cells confirmed that 2’-FL inhibits the binding of DC-SIGN to Leb. Molecular dynamics (MD) simulations show that 2’-FL exists in a preorganized bioactive conformation before binding to DC-SIGN and this conformation is retained after binding to DC-SIGN. Leb has more flexible conformations and utilizes two binding modes, which operate one at a time via its two fucoses to bind to DC-SIGN. 2’-FL may have a reduced entropic penalty due to its preorganized state compared to Leb, and it has lower binding enthalpy, suggesting better binding to DC-SIGN. Thus, due to the better binding to DC-SIGN, 2’-FL may replace Leb from its binding pocket in DC-SIGN. MD simulations also showed that 2’-FL does not bind to Langerin. Our studies confirm 2’-FL as a specific ligand for DC-SIGN and suggest that 2’-FL can replace other DC-SIGN ligands from its binding pocket during ligand-receptor interactions in possible immunomodulatory processes.

Parkinson’s disease patients suffer from both motor and nonmotor impairments. There is currently no cure for Parkinson’s disease, and the most commonly used treatment, levodopa, only functions as a temporary relief of motor symptoms. Inhibition of the expression of the L‐tryptophan‐catabolizing enzyme tryptophan 2,3‐dioxygenase (TDO) has been shown to inhibit aging‐related α‐synuclein toxicity in Caenorhabditis elegans. To evaluate TDO inhibition as a potential therapeutic strategy for Parkinson’s disease, a brain‐penetrable, small molecule TDO inhibitor was developed, referred to as NTRC 3531‐0. This compound potently inhibits human and mouse TDO in biochemical and cell‐based assays and is selective over IDO1, an evolutionary unrelated enzyme that catalyzes the same reaction. In mice, NTRC 3531‐0 increased plasma and brain L‐tryptophan levels after oral administration, demonstrating inhibition of TDO activity in vivo. The effect on Parkinson’s disease symptoms was evaluated in a rotenone‐induced Parkinson’s disease mouse model. A structurally dissimilar TDO inhibitor, LM10, was evaluated in parallel. Both inhibitors had beneficial effects on rotenone‐induced motor and cognitive dysfunction as well as rotenone‐induced dopaminergic cell loss and neuroinflammation in the substantia nigra. Moreover, both inhibitors improved intestinal transit and enhanced colon length, which indicates a reduction of the rotenone‐induced intestinal dysfunction. Consistent with this, mice treated with TDO inhibitor showed decreased expression of rotenone‐induced glial fibrillary acidic protein, which is a marker of enteric glial cells, and decreased α‐synuclein accumulation in the enteric plexus. Our data support TDO inhibition as a potential therapeutic strategy to decrease motor, cognitive, and gastrointestinal symptoms in Parkinson’s disease., Using two selective small molecule inhibitors, the inhibition of tryptophan 2,3‐dioxygenase (TDO) was validated as a potential new therapeutic approach for Parkinson's disease. In a rotenone‐induced mouse model of Parkinson's disease, TDO inhibitor treatment induced positive effects on central nervous system function. Moreover, in contrast to standard therapy, the TDO inhibitors acted peripherally on the intestinal phenotype by reducing the rotenone‐induced intestinal inflammatory response.

This article provides an overview of the design and methodology of the “Corona lockdown: how fit are you?” (CLOFIT) study, including the questionnaires and scales that were included in the online survey. The aim of the CLOFIT study was to investigate the psychosocial and health consequences of the coronavirus disease 2019 (COVID-19) pandemic in the Netherlands. The survey was conducted among the Dutch population to collect data on immune fitness and the psychological and health consequences of the 2019 coronavirus disease (COVID-19) pandemic lockdown in the Netherlands. The CLOFIT dataset contains measures from N = 1910 participants and is broadly representative of the Dutch general population. The dataset represents both sexes, a range of ages including the elderly, different education levels, and ethnic backgrounds. The cohort also includes people with a diverse health status and range of medication use.

In the western world the prevalence of atopic diseases such as food allergies is increasing highly significantly. One of the earliest and most prevalent food allergies occurring in the first year of life is cow's milk allergy. No treatment is available and only avoidance of the cow's milk allergens prevents the occurrence of an allergic reaction. Since cow's milk allergic children have an increased risk of developing other allergies later in life, investigating nutritional strategies to prevent the development of cow's milk allergy by developing oral tolerance is of high interest. Nutritional components such as prebiotics, probiotics, synbiotics and long-chain polyunsaturated fatty acids possess potential to support the maturation of the immune system early in life that might prevent the development of cow's milk allergy. The available research, so far, shows promising results particularly on the development of eczema. However, the preventive effects of the nutritional interventions on the development of food allergy are inconclusive. Future research may benefit from the combination of various dietary components. To clarify the preventive effects of the nutritional components in food allergy more randomized clinical trials are needed.

The composition and activity of the intestinal microbial community structures can be beneficially modulated by nutritional components such as non‐digestible oligosaccharides and omega‐3 poly‐unsaturated fatty acids (n‐3 PUFAs). These components affect immune function, brain development and behaviour. We investigated the additive effect of a dietary combination of scGOS:lcFOS and n‐3 PUFAs on caecal content microbial community structures and development of the immune system, brain and behaviour from day of birth to early adulthood in healthy mice. Male BALB/cByJ mice received a control or enriched diet with a combination of scGOS:lcFOS (9:1) and 6% tuna oil (n‐3 PUFAs) or individually scGOS:lcFOS (9:1) or 6% tuna oil (n‐3 PUFAs). Behaviour, caecal content microbiota composition, short‐chain fatty acid levels, brain monoamine levels, enterochromaffin cells and immune parameters in the mesenteric lymph nodes (MLN) and spleen were assessed. Caecal content microbial community structures displayed differences between the control and dietary groups, and between the dietary groups. Compared to control diet, the scGOS:lcFOS and combination diets increased caecal saccharolytic fermentation activity. The diets enhanced the number of enterochromaffin cells. The combination diet had no effects on the immune cells. Although the dietary effect on behaviour was limited, serotonin and serotonin metabolite levels in the amygdala were increased in the combination diet group. The combination and individual interventions affected caecal content microbial profiles, but had limited effects on behaviour and the immune system. No apparent additive effect was observed when scGOS:lcFOS and n‐3 PUFAs were combined. The results suggest that scGOS:lcFOS and n‐3 PUFAs together create a balance—the best of both in a healthy host.

International audience; Autism Spectrum Disorder (ASD) is a set of neurodevelopmental disorders characterised by behavioural impairment and deficiencies in social interaction and communication. A recent study estimated that 1 in 89 children have developed some form of ASD in European countries. Moreover, there is no specific treatment and since ASD is not a single clinical entity, the identification of molecular biomarkers for diagnosis remains challenging. Besides behavioural deficiencies, individuals with ASD often develop comorbid medical conditions including intestinal problems, which may reflect aberrations in the bidirectional communication between the brain and the gut. The impact of faecal microbial composition in brain development and behavioural functions has been repeatedly linked to ASD, as well as changes in the metabolic profile of individuals affected by ASD. Since metabolism is one of the major drivers of microbiome–host interactions, this review aims to report emerging literature showing shifts in gut microbiota metabolic function in ASD. Additionally, we discuss how these changes may be involved in and/or perpetuate ASD pathology. These valuable insights can help us to better comprehend ASD pathogenesis and may provide relevant biomarkers for improving diagnosis and identifying new therapeutic targets.

Introduction: The aim of this cross-sectional study was to investigate the association between a healthier diet, perceived immune fitness, and biomarkers of the immune system. Methods: N = 108 participants (31 men and 77 women), 18–30 years old, completed a questionnaire, comprising the Healthy Diet Scale (HDS) and a 1-item scale assessing perceived immune fitness. In addition, saliva samples were collected and C-reactive protein (CRP) and cytokine concentrations of interleukin (IL)− 1β and IL-8 were determined. Results: Overall, a significant correlation was found between the HDS score and perceived immune fitness (r = 0.221, p = 0.021), suggesting that a healthier diet was associated with a better immune fitness. The HSD score correlated significantly and negatively with saliva CRP concentrations (r = −0.240, p = 0.013). No significant correlations were found with other biomarkers. In women, the HDS correlated significantly with perceived immune fitness (r = 0.247, p = 0.030) and CRP levels ( r = −0.281, p = 0.014). In men, correlations with perceived immune fitness ( r = −0.219, p = 0.237) and the biomarkers were not significant. Discussion: Significant associations between attaining a healthy diet, perceived immune fitness and CRP were found. More research is needed to investigate the observed sex differences and underlying mechanisms.

Primer sets are short DNA sequences of 18-22 base pairs, that can be used to verify the presence of a virus, and designed to attach to a specific part of a viral DNA. Designing a primer set requires choosing a region of DNA, avoiding the possibility of hybridization to a similar sequence, as well as considering its GC content and Tm (melting temperature). Coronaviruses, such as SARS-CoV-2, have a considerably large genome (around 30 thousand nucleotides) when compared to other viruses. With the rapid rise and spread of SARS-CoV-2 variants, it has become a priority to breach our lack of specific primers available for diagnosis of this new variants. Here, we propose an evolutionary-based approach to primer design, able to rapidly deliver a high-quality primer set for a target sequence of the virus variant. Starting from viral sequences collected from open repositories, the proposed approach is proven able to uncover a specific primer set for the B.1.1.7 SARS-CoV-2 variant. Only recently identified, B.1.1.7 is already considered potentially dangerous, as it presents a considerably higher transmissibility when compared to other variants.