Exosomes have been implicated in numerous biological processes, and they may serve as important disease markers. Surface proteins on exosomes carry information about their tissues of origin. Because of the heterogeneity of exosomes it is desirable to investigate them individually, but this has so far remained impractical. Here, we demonstrate a proximity-dependent barcoding assay to profile surface proteins of individual exosomes using antibody-DNA conjugates and next-generation sequencing. We first validate the method using artificial streptavidin-oligonucleotide complexes, followed by analysis of the variable composition of surface proteins on individual exosomes, derived from human body fluids or cell culture media. Exosomes from different sources are characterized by the presence of specific combinations of surface proteins and their abundance, allowing exosomes to be separately quantified in mixed samples to serve as markers for tissue-specific engagement in disease.

Indoor microbiome exposure is associated with asthma, rhinitis and eczema. However, no studies report the interactions between environmental characteristics, indoor microbiome and health effects in a repeated cross-sectional framework. 1,279 and 1,121 preschool children in an industrial city (Taiyuan) of China were assessed for asthma, rhinitis and eczema symptoms in 2012 and 2019 by self-administered questionnaires, respectively. Bacteria and fungi in classroom vacuum dust were characterized by culture-independent amplicon sequencing. Multi-level logistic/linear regression was performed in two cross-sectional and two combined models to assess the associations. The number of observed species in bacterial and fungal communities in classrooms increased significantly from 2012 to 2019, and the compositions of the microbial communities were drastically changed (p < 0.001). The temporal microbiome variation was significantly larger than the spatial variation within the city (p < 0.001). Annual average outdoor SO₂ concentration decreased by 60.7%, whereas NO₂ and PM₁₀ concentrations increased by 63.3% and 40.0% from 2012 to 2019, which were both associated with indoor microbiome variation (PERMANOVA p < 0.001). The prevalence of asthma (2.0% to 3.3%, p = 0.06) and rhinitis (28.0% to 25.3%, p = 0.13) were not significantly changed, but the prevalence of eczema was increased (3.6% to 7.0%; p < 0.001). Aspergillus subversicolor, Collinsella and Cutibacterium were positively associated with asthma, rhinitis and eczema, respectively (p < 0.01). Prevotella, Lactobacillus iners and Dolosigranulum were protectively (negatively) associated with rhinitis (p < 0.01), consistent with previous studies in the human respiratory tract. NO₂ and PM₁₀ concentrations were negatively associated with rhinitis in a bivariate model, but a multivariate mediation analysis revealed that Prevotella fully mediated the health effects. This is the first study to report the interactions between environmental characteristics, indoor microbiome and health in a repeated cross-sectional framework. The mediating effects of indoor microorganisms suggest incorporating biological with chemical exposure for a comprehensive exposure assessment.

Indoor microbial diversity and composition are suggested to affect the prevalence and severity of asthma by previous home microbiome studies, but no microbiome-health association study has been conducted in a school environment, especially in tropical countries. In this study, we collected floor dust and environmental characteristics from 21 classrooms, and health data related to asthma symptoms from 309 students, in junior high schools in Johor Bahru, Malaysia. The bacterial and fungal composition was characterized by sequencing 16s rRNA gene and internal transcribed spacer (ITS) region, and the absolute microbial concentration was quantified by qPCR. In total, 326 bacterial and 255 fungal genera were characterized. Five bacterial (Sphingobium, Rhodomicrobium, Shimwellia, Solirubrobacter, Pleurocapsa) and two fungal (Torulaspora and Leptosphaeriaceae) taxa were protective for asthma severity. Two bacterial taxa, Izhakiella and Robinsoniella, were positively associated with asthma severity. Several protective bacterial taxa including Rhodomicrobium, Shimwellia and Sphingobium have been reported as protective microbes in previous studies, whereas other taxa were first time reported. Environmental characteristics, such as age of building, size of textile curtain per room volume, occurrence of cockroaches, concentration of house dust mite allergens transferred from homes by the occupants, were involved in shaping the overall microbial community but not asthma-associated taxa; whereas visible dampness and mold, which did not change the overall microbial community for floor dust, was negatively associated with the concentration of protective bacteria Rhodomicrobium (β = -2.86, p = 0.021) of asthma. The result indicates complex interactions between microbes, environmental characteristics and asthma symptoms. Overall, this is the first indoor microbiome study to characterize the asthma-associated microbes and their environmental determinant in the tropical area, promoting the understanding of microbial exposure and respiratory health in this region.

Background: Studies in developed countries have reported that the prevalence of asthma and rhinitis is higher in urban areas than in rural areas, and this phenomenon is associated with urbanization and changing indoor microbiome exposure. Developing countries such as China have experienced rapid urbanization in past years, but no study has investigated microbiome exposure and urban-rural health effects in these countries. Methods: Nine high schools from urban and rural areas were randomly selected in Shanxi Province, China, and classroom vacuum dust was collected for shotgun metagenomic sequencing. A self-administered questionnaire was collected from 1332 students for personal information and health data. Three-level logistic regression was performed between microbial richness/abundance/functional pathways and the occurrence of asthma and rhinitis symptoms. Results: Consistent with developed countries, the prevalence of wheeze and rhinitis was higher in urban areas than in rural areas (p < 0.05). Metagenomic profiling revealed 8302 bacterial, 395 archaeal, 744 fungal, 524 protist and 1103 viral species in classroom dust. Actinobacteria (mean relative abundance 49.7%), Gammaproteobacteria (18.4%) and Alphaproteobacteria (10.0%) were the most abundant bacterial classes. The overall microbiome composition was significantly different between urban and rural schools (p = 0.001, Adonis). Species from Betaproteobactera, Gammaproteobacteria and Bacilli were enriched in urban schools, and species from Actinobacteria and Cyanobacteria were enriched in rural schools. Potential pathogens were present in higher abundance in urban schools than in rural schools (p < 0.05). Pseudoalteromonas, Neospora caninum and Microbacterium foliorum were positively associated with the occurrence of wheeze, rhinitis and rhinoconjunctivitis, and Brachybacterium was protectively (negatively) associated with rhinitis (p < 0.01). The abundance of human endocrine and metabolic disease pathways was positively associated with rhinitis (p = 0.008), and butyrate and propionate metabolic genes and pathways were significantly enriched in rural schools (p < 0.005), in line with previous findings that these short-chain fatty acids protect against inflammatory diseases in the human gut. Conclusions: We conducted the first indoor microbiome survey in urban/rural environments with shotgun metagenomics, and the results revealed high-resolution microbial taxonomic and functional profiling and potential health effects.

A common feature of eukaryote genomes is large chromosomal regions where recombination is absent or strongly reduced, but the factors that cause this reduction are not well understood. Genomic rearrangements have often been implicated, but they may also be a consequence of recombination suppression rather than a cause. In this study, we generate eight high-quality genomic data sets of the filamentous ascomycete Neurospora tetrasperma, a fungus that lacks recombination over most of its largest chromosome. The genomes surprisingly reveal collinearity of the non-recombining regions and although large inversions are enriched in these regions, we conclude these inversions to be derived and not the cause of the suppression. To our knowledge, this is the first time that non-recombining, genic regions as large as 86% of a full chromosome (or 8 Mbp), are shown to be collinear. These findings are of significant interest for our understanding of the evolution of sex chromosomes and other supergene complexes.