The microbiome plays a fundamental role in how the immune system develops and how inflammatory responses are shaped and regulated. The “gut-lung axis” is a relatively new term that highlights a crucial biological crosstalk between the intestinal microbiome and lung. A growing body of literature suggests that dysbiosis, perturbation of the gut microbiome, is a driving force behind the development, and severity of allergic asthma. Animal models have given researchers new insights into how gut microbe-derived components and metabolites, such as short-chain fatty acids (SCFAs), influence the development of asthma. While the full understanding of how SCFAs influence allergic airway disease remains obscure, a recurring theme of epigenetic regulation of gene expression in several immune cell compartments is emerging. This review will address our current understanding of how SCFAs, and specifically butyrate, orchestrates cell behavior, and epigenetic changes and will provide a detailed overview of the effects of these modifications on immune cells in the context of allergic airway disease.

Neurofilaments: light, medium, and heavy (abbreviated as NF-L, NF-M, and NF-H, respectively), which belong to Type IV intermediate filament family (IF), are neuron-specific cytoskeletal components. Neurofilaments are axonal structural components and integral components of synapses, which are important for neuronal electric signal transmissions along the axons and post-translational modification. Abnormal assembly of neurofilaments is found in several human neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), infantile spinal muscular atrophy (SMA), and hereditary sensory-motor neuropathy (HSMN). In addition, those pathological neurofilament accumulations are known in α-synuclein in Parkinson’s disease (PD), Aβ and tau in Alzheimer’s disease (AD), polyglutamine in CAG trinucleotide repeat disorders, superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP43), neuronal FUS proteins, optineurin (OPTN), ubiquilin 2 (UBQLN2), and dipeptide repeat protein (DRP) in amyotrophic lateral sclerosis (ALS). When axon damage occurs in central nervous disorders, neurofilament proteins are released and delivered into cerebrospinal fluid (CSF), which are then circulated into blood. New quantitative analyses and assay techniques are well-developed for the detection of neurofilament proteins, particularly NF-L and the phosphorylated NF-H (pNF-H) in CSF and serum. This review discusses the potential of using peripheral blood NF quantities and evaluating the severity of damage in the nervous system. Intermediate filaments could be promising biomarkers for evaluating disease progression in different nervous system disorders.

Background: Patients with chronic obstructive pulmonary disease (COPD) are commonly treated with inhaled corticosteroid/long-acting ß2-agonist combination therapy. While previous studies have investigated the host–microbiome interactions in COPD, the effects of specific steroid formulations on this complex cross-talk remain obscure. Methods: We collected and evaluated data from the Study to Investigate the Differential Effects of Inhaled Symbicort and Advair on Lung Microbiota (DISARM), a randomized controlled trial. Bronchoscopy was performed on COPD patients before and after treatment with salmeterol/fluticasone, formoterol/budesonide or formoterol-only. Bronchial brush samples were processed for microbial 16S rRNA gene sequencing and host mRNA sequencing. Longitudinal changes in the microbiome at a community, phylum and genus level were correlated with changes in host gene expression using a Spearman’s rank correlation test. Findings: In COPD patients treated with salmeterol/fluticasone, the expression levels of 676 host genes were significantly correlated to changes in the alpha diversity of the small airways. At a genus level, the expression levels of 122 host genes were significantly related to changes in the relative abundance of Haemophilus. Gene enrichment analyses revealed the enrichment of pathways and biological processes related to innate and adaptive immunity and inflammation. None of these changes were evident in patients treated with formoterol/budesonide or formoterol alone. Interpretation: Changes in the microbiome following salmeterol/fluticasone treatment are related to alterations in the host transcriptome in the small airways of patients with COPD. These data may provide insights into why some COPD patients treated with inhaled corticosteroids may be at an increased risk for airway infection, including pneumonia. Funding: The Canadian Institute of Health Research, the British Columbia Lung Association, and an investigator-initiated grant from AstraZeneca.

Background: Approximately 10% of individuals who recover from COVID-19 experience residual respiratory symptoms impacting their quality of life, but the mechanisms behind pulmonary long COVID (PLC) are largely unknown. Objectives: We characterized airway and circulating immune cells in patients with and without PLC. Methods: Participants were recruited and allocated into two groups: 1) PLC, defined by a St. George’s Respiratory Questionnaire (SGRQ) total score of >10 at least three months following an acute SARS-CoV-2 infection with self-reported new or worsening symptoms, and 2) controls, defined by SGRQ =<10 with or without a prior history of COVID. We performed research bronchoscopy and obtained bronchoalveolar lavage (BAL) in seven PLC patients and seven age- and sex-matched control subjects. Single-cell RNA sequencing (scRNAseq) was performed on the BAL cells. Peripheral blood mononuclear cells (PBMCs) were cryopreserved in 30 participants (17 PLC, 13 controls) for proteomic analysis. Serum was submitted for microarray detection of auto-IgG antibodies. Methods: We annotated 105,836 cells using scRNAseq and found that CD4+ T-cells were credibly increased in participants with PLC. scRNAseq also revealed up-regulation of anti-viral pathways including those related to interferon signaling in T-cells as well as antigen presenting cells. In PBMCs, T-cells expressing both CD4 and CD8 were elevated in PLC participants. Autoantibodies targeting genomic DNA, collagen II, and TIF-gamma were significantly increased in PLC patients. Conclusions: PLC is associated with dysregulation of T-cell mediated immunity, which may be related to autoimmunity. These cells represent potential novel therapeutic targets in patients suffering from PLC.