Analyzing human as well as animal microbiota composition has gained growing interest because structural components and metabolites of microorganisms fundamentally influence all aspects of host physiology. Originally dominated by culture-dependent methods for exploring these ecosystems, the development of molecular techniques such as high throughput sequencing has dramatically increased our knowledge. Because many studies of the microbiota are based on the bacterial 16S ribosomal RNA (rRNA) gene targets, they can, at least in principle, be compared to determine the role of the microbiome composition for developmental processes, host metabolism, and physiology as well as different diseases. In our review, we will summarize differences and pitfalls in current experimental protocols, including all steps from nucleic acid extraction to bioinformatical analysis which may produce variation that outweighs subtle biological differences. Future developments, such as integration of metabolomic, transcriptomic, and metagenomic data sets and standardization of the procedures, will be discussed.

It is not clear whether there is an association between adverse reactions and immune response after vaccination. Seven hundred and thirty-five vaccinees from our University Medical Center vaccination clinic provided information about sex, age and adverse reactions after first and second vaccination with BNT162b2. Adverse reactions were categorized into three groups: no or minor on the injection side, moderate (not further classified) and severe—defined as any symptom(s) resulting in sick leave. We chose 38 vaccinees with the most severe adverse reactions and compared their humoral and T-cell-mediated immune responses after second vaccination with those of 38 sex and age matched controls without or only minor injection-side related adverse reactions. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-receptor binding domain (RBD) IgG titers were detectable in all participants (median 5528; range 958–26,285). Men with severe adverse reactions had 1.5-fold higher median SARS-CoV-2 RBD IgG titers compared to men without adverse reactions (median 7406 versus 4793; p < 0.001). Similarly; neutralization activity was significantly higher in men with severe adverse reactions (half maximal inhibitory concentrations (IC₅₀) median 769 versus 485; p < 0.001). Reactogenicity did not influence humoral immune response in women nor T-cell-mediated immune response in any sex. To conclude; adverse reactions after vaccination with BNT162b2 do influence humoral immune response yet only in men and are not a prerequisite for a robust antibody response.

The current antimicrobial therapy of bacterial infections of the central nervous system (CNS) in adults and pediatric patients is faced with many pitfalls as the drugs have to reach necessary levels in serum and cross the blood-brain barrier. Furthermore, several studies report that different factors such as the structure of the antimicrobial agent, the severity of disease, or the degree of inflammation play a significant role. Despite the available attempts to establish pharmacokinetic (PK) modeling to improve the required dosing regimen for adults and pediatric patients, conclusive recommendations for the best therapeutic strategies are still lacking. For instance, bacterial meningitis, the most common CNS infections, and ventriculitis, a severe complication of meningitis, are still associated with 10% and 30% mortality, respectively. Several studies report on the use of vancomycin and meropenem to manage meningitis and ventriculitis; therefore, this review aims to shed light on the current knowledge about their use in adults and pediatric patients. Consequently, studies published from 2015 until mid-July 2021 are included, and data about the study population, levels of drugs in serum and cerebrospinal fluid (CSF), and measured PK data in serum and CSF are provided. The overall aim is to provide the readers a recent reference that summarizes the pitfalls and success of the current therapy and emphasizes the importance of performing more studies to improve the clinical outcome of the current therapeutical approach.

Adequate perception of immunologically important pathogen-associated molecular patterns like lipopolysaccharide and bacterial lipoproteins is essential for efficient innate and adaptive immune responses. In the context of Gram-negative infection, bactericidal/permeability-increasing protein (BPI) neutralizes endotoxic activity of lipopolysaccharides, and thus prohibits hyperactivation. So far, no immunological function of BPI has been described in Gram-positive infections. Here, we show a significant elevation of BPI in Gram-positive meningitis and, surprisingly, a positive correlation between BPI and pro-inflammatory markers like TNFα. To clarify the underlying mechanisms, we identify BPI ligands of Gram-positive origin, specifically bacterial lipopeptides and lipoteichoic acids, and determine essential structural motifs for this interaction. Importantly, the interaction of BPI with these newly defined ligands significantly enhances the immune response in peripheral blood mononuclear cells (PBMCs) mediated by Gram-positive bacteria, and thereby ensures their sensitive perception. In conclusion, we define BPI as an immune enhancing pattern recognition molecule in Gram-positive infections.

High throughput sequencing of bacterial 16S rRNA genes and metagenomes were applied to analyze complex microbial communities inhabiting the human gut and other body sites, and their role in numerous diseases. Studies in animals were important for elucidating the effects of the gut microbiota on the brain and behavior, and the responsible mechanisms. Recent studies in patients have identified bacterial taxa of the gut microbiome possibly impacting different neurological and psychiatric disorders including ADHD. Furthermore, antibiotic treatment of infections globally shape compositions of gut microbiota and might indirectly influence ADHD development. However, published studies revealed still partially incongruent results. Potential reasons for the still ill defined role of gut microbiota in ADHD comprise a) different study designs b) small number of patients c) different age groups analyzed d) inclusion of only treatment naive patients versus patients under medication e) differences of males versus females ratios and f) the heterogenous technology applied for microbiome sequence analysis. Furthermore, the complex interplay between the gut microbiome and individual host genetic factors requires much larger sample sizes and additional patient genome information. Alternative treatment options like probiotics or dietary interventions for ADHD therapy might offer new opportunities to prevent or treat this increasingly common disease. Clearly, further studies are needed to clarify molecular mechanisms imparting the gut brain axis as basis to modify commensal microbiota or their functions to target ADHD. The purpose of this review is to evaluate the most recent literature on the role of the gut microbiome in ADHD.