Environmental determinants and demographic influences on global urban microbiomes, antimicrobial resistance and pathogenicity.

Urban microbiome plays crucial roles in human health and are related to various diseases. The MetaSUB Consortium has conducted the most comprehensive global survey of urban microbiomes to date, profiling microbial taxa/functional genes across 60 cities worldwide. However, the influence of environmental/demographic factors on urban microbiome remains to be elucidated. We collected 35 environmental and demographic characteristics to examine their effects on global urban microbiome diversity/composition by PERMANOVA and regression models. PM10 concentration was the primary determinant factor positively associated with microbial α-diversity (observed species: p = 0.004, ß = 1.66, R2 = 0.46; Fisher's alpha: p = 0.005, ß = 0.68, R2 = 0.43), whereas GDP per capita was negatively associated (observed species: p = 0.046, ß = -0.70, R2 = 0.10; Fisher's alpha: p = 0.004, ß = -0.34, R2 = 0.22). The ß-diversity of urban microbiome was shaped by seven environmental characteristics, including Köppen climate type, vegetation type, greenness fraction, soil type, PM2.5 concentration, annual average precipitation and temperature (PERMANOVA, p < 0.001, R2 = 0.01-0.06), cumulatively accounted for 20.3% of the microbial community variance. Canonical correspondence analysis (CCA) identified microbial species most strongly associated with environmental characteristic variation. Cities in East Asia with higher precipitation showed an increased abundance of Corynebacterium metruchotii, and cities in America with a higher greenness fraction exhibited a higher abundance of Corynebacterium casei. The prevalence of antimicrobial resistance (AMR) genes were negatively associated with GDP per capita and positively associated with solar radiation (p < 0.005). Total pathogens prevalence was positively associated with urban population and negatively associated with average temperature in June (p < 0.05). Our study presents the first comprehensive analysis of the influence of environmental/demographic characteristics on global urban microbiome. Our findings indicate that managing air quality and urban greenness is essential for regulating urban microbial diversity and composition. Meanwhile, socio-economic considerations, particularly reducing antibiotic usage in regions with lower GDP, are paramount in curbing the spread of antimicrobial resistance in urban environments.

The Role of Indoor Microbiome and Metabolites in Shaping Children's Nasal and Oral Microbiota: A Pilot Multi-Omic Analysis.

Maintaining a diverse and well-balanced nasal and oral microbiota is vital for human health. However, the impact of indoor microbiome and metabolites on nasal and oral microbiota remains largely unknown. Fifty-six children in Shanghai were surveyed to complete a questionnaire about their personal and environmental characteristics. The indoor microbiome and metabolites from vacuumed indoor dust were profiled via shotgun metagenomics and untargeted liquid chromatography-mass spectrometry (LC-MS). The nasal and oral microbiota in children was characterized using full-length 16S rRNA sequencing from PacBio. Associations between personal/environmental characteristics and the nasal/oral microbiota were calculated using PERMANOVA and regression analyses. We identified 6247, 431, and 342 microbial species in the indoor dust, nasal, and oral cavities, respectively. The overall nasal and oral microbial composition showed significant associations with environmental tobacco smoke (ETS) exposure during pregnancy and early childhood (p = 0.005 and 0.03, respectively), and the abundance of total indoor flavonoids and two mycotoxins (deoxynivalenol and nivalenol) (p = 0.01, 0.02, and 0.03, respectively). Notably, the abundance of several flavonoids, such as baicalein, eupatilin, isoliquiritigenin, tangeritin, and hesperidin, showed positive correlations with alpha diversity and the abundance of protective microbial taxa in nasal and oral cavities (p < 0.02), suggesting their potential beneficial roles in promoting nasal/oral health. Conversely, high carbohydrate/fat food intake and ETS exposure diminished protective microorganisms while augmenting risky microorganisms in the nasal/oral cavities. Further, potential microbial transfer was observed from the indoor environment to the childhood oral cavity (Moraxella catarrhalis, Streptococcus mitis, and Streptococcus salivarius), which could potentially increase virulence factors related to adherence and immune modulation and vancomycin resistance genes in children. This is the first study to reveal the association between the indoor microbiome/metabolites and nasal/oral microbiota using multi-omic approaches. These findings reveal potential protective and risk factors related to the indoor microbial environment.

Microbial Virulence Factors, Antimicrobial Resistance Genes, Metabolites, and Synthetic Chemicals in Cabins of Commercial Aircraft.

Passengers are at a higher risk of respiratory infections and chronic diseases due to microbial exposure in airline cabins. However, the presence of virulence factors (VFs), antimicrobial resistance genes (ARGs), metabolites, and chemicals are yet to be studied. To address this gap, we collected dust samples from the cabins of two airlines, one with textile seats (TSC) and one with leather seats (LSC), and analyzed the exposure using shotgun metagenomics and LC/MS. Results showed that the abundances of 17 VFs and 11 risk chemicals were significantly higher in TSC than LSC (p < 0.01). The predominant VFs in TSC were related to adherence, biofilm formation, and immune modulation, mainly derived from facultative pathogens such as Haemophilus parainfluenzae and Streptococcus pneumoniae. The predominant risk chemicals in TSC included pesticides/herbicides (carbofuran, bromacil, and propazine) and detergents (triethanolamine, diethanolamine, and diethyl phthalate). The abundances of these VFs and detergents followed the trend of TSC > LSC > school classrooms (p < 0.01), potentially explaining the higher incidence of infectious and chronic inflammatory diseases in aircraft. The level of ARGs in aircraft was similar to that in school environments. This is the first multi-omic survey in commercial aircraft, highlighting that surface material choice is a potential intervention strategy for improving passenger health.

Associations between environmental characteristics, high-resolution indoor microbiome, metabolome and allergic and non-allergic rhinitis symptoms for junior high school students.

Rhinitis is one of the most prevalent chronic diseases globally. Microbiome exposure affects the occurrence of rhinitis. However, previous studies did not differentiate allergic rhinitis (AR) and non-allergic rhinitis (NAR) in the microbial association analysis. In this study, we investigate 347 students in 8 junior high schools, Terengganu, Malaysia, who were categorized as healthy (70.9%), AR (13.8%) and NAR (15.3%) based on a self-administered questionnaire and skin prick tests of pollen, pet, mould and house dust mite allergens. Classroom microbial and metabolite exposure in vacuumed dust was characterized by PacBio long-read amplicon sequencing, quantitative PCR and LC-MS-based untargeted metabolomics. Our findings indicate a similar microbial association pattern between AR and NAR. The richness in Gammaproteobacteria was negatively associated with AR and NAR symptoms, whereas total fungal richness was positively associated with AR and NAR symptoms (p < 0.05). Brasilonema bromeliae and Aeromonas enteropelogenes were negatively associated with AR and NAR, and Deinococcus was positively associated with AR and NAR (p < 0.01). Pipecolic acid was protectively associated with AR and NAR symptoms (OR = 0.06 and 0.13, p = 0.009 and 0.045). A neural network analysis showed that B. bromeliae was co-occurring with pipecolic acid, suggesting that the protective role of this species may be mediated by releasing pipecolic acid. Indoor relative humidity and the weight of vacuum dust were associated with AR and NAR, respectively (p < 0.05), but the health effects were mediated by two protective bacterial species, Aliinostoc morphoplasticum and Ilumatobacter fluminis. Overall, our study reported a similar microbial association pattern between AR and NAR and also revealed the complex interactions between microbial species, environmental characteristics, and rhinitis symptoms.

Indoor metabolites and chemicals outperform microbiome in classifying childhood asthma and allergic rhinitis.

Indoor microorganisms impact asthma and allergic rhinitis (AR), but the associated microbial taxa often vary extensively due to climate and geographical variations. To provide more consistent environmental assessments, new perspectives on microbial exposure for asthma and AR are needed. Home dust from 97 cases (32 asthma alone, 37 AR alone, 28 comorbidity) and 52 age- and gender-matched controls in Shanghai, China, were analyzed using high-throughput shotgun metagenomic sequencing and liquid chromatography-mass spectrometry. Homes of healthy children were enriched with environmental microbes, including Paracoccus, Pseudomonas, and Psychrobacter, and metabolites like keto acids, indoles, pyridines, and flavonoids (astragalin, hesperidin) (False Discovery Rate < 0.05). A neural network co-occurrence probability analysis revealed that environmental microorganisms were involved in producing these keto acids, indoles, and pyridines. Conversely, homes of diseased children were enriched with mycotoxins and synthetic chemicals, including herbicides, insecticides, and food/cosmetic additives. Using a random forest model, characteristic metabolites and microorganisms in Shanghai homes were used to classify high and low prevalence of asthma/AR in an independent dataset in Malaysian schools (N = 1290). Indoor metabolites achieved an average accuracy of 74.9% and 77.1% in differentiating schools with high and low prevalence of asthma and AR, respectively, whereas indoor microorganisms only achieved 51.0% and 59.5%, respectively. These results suggest that indoor metabolites and chemicals rather than indoor microbiome are potentially superior environmental indicators for childhood asthma and AR. This study extends the traditional risk assessment focusing on allergens or air pollutants in childhood asthma and AR, thereby revealing potential novel intervention strategies for these diseases.

Phosphorylation-mediated interaction between human E26 transcription factor 1 and specific protein 1 is required for tumor cell migration.

Transcription factors, human E26 transcription factor 1 (Ets1) and specific protein 1 (Sp1), are known to induce gene expression in tumorigenicity. High Ets1 expression is often associated with colorectal tumorigenesis. In this study, we discover that metastasis and clone formation in SW480 cells mainly depend on the direct interaction between Ets1 and Sp1 instead of high Ets1 expression. The interaction domains are further addressed to be the segment at Sp1(626-708) and the segment at Ets1(244-331). In addition, the phosphorylation inhibition of Ets1 at Tyr283 by either downregulation of Src kinase or Src family inhibitor treatment decreases the interaction between Sp1 and Ets1 and suppresses SW480 migration. Either administration or overexpression of the peptides harboring the interaction segment strongly inhibits the colony formation and migration of SW480 cells. Our findings suggest that the interaction between Ets1 and Sp1 rather than Ets1 alone promotes transformation in SW480 cells and provide new insight into the Ets1 and Sp1 interaction as an antitumour target in SW480 cells.

Indoor microbiome, microbial and plant metabolites, chemical compounds, and asthma symptoms in junior high school students: a multicentre association study in Malaysia.

BACKGROUND: Indoor microbial exposure is associated with asthma, but the health effects of indoor metabolites and chemicals have not been comprehensively assessed. METHODS: We collected classroom dust from 24 junior high schools in three geographically distanced areas in Malaysia (Johor Bahru, Terengganu and Penang), and conducted culture-independent high-throughput microbiome and untargeted metabolomics/chemical profiling. RESULTS: 1290 students were surveyed for asthma symptoms (wheeze). In each centre, we found significant variation in the prevalence of wheeze among schools, which could be explained by personal characteristics and air pollutants. Large-scale microbial variations were observed between the three centres; the potential protective bacteria were mainly from phyla Actinobacteria in Johor Bahru, Cyanobacteria in Terengganu and Proteobacteria in Penang. In total, 2633 metabolites and chemicals were characterised. Many metabolites were enriched in low-wheeze schools, including plant secondary metabolites flavonoids/isoflavonoids (isoliquiritigenin, formononetin, astragalin), indole and derivatives (indole, serotonin, 1H-indole-3-carboxaldehyde), and others (biotin, chavicol). A neural network analysis showed that the indole derivatives were co-occurring with the potential protective microbial taxa, including Actinomycetospora, Fischerella and Truepera, suggesting these microorganisms may pose health effects by releasing indole metabolites. A few synthetic chemicals were enriched in high-wheeze schools, including pesticides (2(3H)-benzothiazolethione), fragrances (2-aminobenzoic acid, isovaleric acid), detergents and plastics (phthalic acid), and industrial materials (4,4-sulfonyldiphenol). CONCLUSIONS: This is the first association study between high-throughput indoor chemical profiling and asthma symptoms. The consistent results from the three centres indicate that indoor metabolites/chemicals could be a better indicator than the indoor microbiome for environmental and health assessments, providing new insights for asthma prediction, prevention and control.

Indoor microbiome, air pollutants and asthma, rhinitis and eczema in preschool children - A repeated cross-sectional study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 microbiome and allergic diseases: From theoretical advances to prevention strategies.

The prevalence of allergic diseases, such as asthma, rhinitis, eczema, and sick building syndrome (SBS), has increased drastically in the past few decades. Current medications can only relieve the symptoms but not cure these diseases whose development is suggested to be greatly impacted by the indoor microbiome. However, no study comprehensively summarizes the progress and general rules in the field, impeding subsequent translational application. To close knowledge gaps between theoretical research and practical application, we conducted a comprehensive literature review to summarize the epidemiological, environmental, and molecular evidence of indoor microbiome studies. Epidemiological evidence shows that the potential protective indoor microorganisms for asthma are mainly from the phyla Actinobacteria and Proteobacteria, and the risk microorganisms are mainly from Bacilli, Clostridia, and Bacteroidia. Due to extremely high microbial diversity and geographic variation, different health-associated species/genera are detected in different regions. Compared with indoor microbial composition, indoor metabolites show more consistent associations with health, including microbial volatile organic compounds (MVOCs), lipopolysaccharides (LPS), indole derivatives, and flavonoids. Therefore, indoor metabolites could be a better indicator than indoor microbial taxa for environmental assessments and health outcome prediction. The interaction between the indoor microbiome and environmental characteristics (surrounding greenness, relative humidity, building confinement, and CO2 concentration) and immunology effects of indoor microorganisms (inflammatory cytokines and pattern recognition receptors) are briefly reviewed to provide new insights for disease prevention and treatment. Widely used tools in indoor microbiome studies are introduced to facilitate standard practice and the precise identification of health-related targets.

Distinct gut microbiota and health outcomes in asymptomatic infection, viral nucleic acid test re-positive, and convalescent COVID-19 cases.

Gut microbiota composition is suggested to associate with coronavirus disease 2019 (COVID-19) severity, but the impact of gut microbiota on health outcomes is largely unclear. We recruited 81 individuals from Wuhan, China, including 13 asymptomatic infection cases (Group A), 24 COVID-19 convalescents with adverse outcomes (Group C), 31 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) re-positive cases (Group D), and 13 non-COVID-19 healthy controls (Group H). The microbial features of Groups A and D were similar and exhibited higher gut microbial diversity and more abundant short-chain fatty acid (SCFA)-producing species than Group C. Group C was enriched with opportunistic pathogens and virulence factors related to adhesion and toxin production. The abundance of SCFA-producing species was negatively correlated, while Escherichia coli was positively correlated with adverse outcomes. All three groups (A, C, and D) were enriched with the mucus-degrading species Akkermansia muciniphila, but decreased with Bacteroides-encoded carbohydrate-active enzymes. The pathways of vitamin B6 metabolic and folate biosynthesis were decreased, while selenocompound metabolism was increased in the three groups. Specifically, the secondary bile acid (BA) metabolic pathway was enriched in Group A. Antibiotic resistance genes were common among the three groups. Conclusively, the gut microbiota was related to the health outcomes of COVID-19. Dietary supplementations (SCFAs, BA, selenium, folate, vitamin B6) may be beneficial to COVID-19 patients.

Classroom microbiome, functional pathways and sick-building syndrome (SBS) in urban and rural schools - Potential roles of indoor microbial amino acids and vitamin metabolites.

Sick building symptoms (SBS) are defined as non-specific symptoms related to indoor exposures, including mucosal symptoms in eye, nose, throat, and skin, and general symptoms as headache and tiredness. Indoor microbial composition is associated with SBS symptoms, but the impact of microbial functional genes and potential metabolic products has not been characterized. We conducted a shotgun microbial metagenomic sequencing for vacuum dust collected in urban and rural schools in Shanxi province, China. SBS symptoms in students were surveyed, and microbial taxa and functional pathways related to the symptoms were identified using a multi-level linear regression model. SBS symptoms were common in students, and the prevalence of ocular and throat symptoms, headache, and tiredness was higher in urban than in rural areas (p < 0.05). A significant higher microbial α-diversity was found in rural areas than in urban areas (Chao1, p = 0.001; ACE, p = 0.002). Also, significant variation in microbial taxonomic and functional composition (ß-diversity) was observed between urban and rural areas (p < 0.005). Five potential risk Actinobacteria species were associated with SBS symptoms (p < 0.01); students in the classrooms with a higher abundance of an unclassified Geodermatophilaceae, Geodermatophilus, Fridmanniella luteola, Microlunatus phosphovorus and Mycetocola reported more nasal and throat symptoms and tiredness. Students with a higher abundance of an unclassified flavobacteriaceae reported fewer throat symptoms and tiredness. The abundance of microbial metabolic pathways related to the synthesis of B vitamins (biotin and folate), gamma-aminobutyric acid (GABA), short-chain fatty acids (SCFAs), and peptidoglycan and were protectively (negatively) associated with SBS symptoms (FDR < 0.05). The result is consistent with human microbiota studies, which reported that these microbial products are extensively involved in immunological processes and anti-inflammatory effects. This is the first study to report the functional potential of the indoor microbiome and the occurrence of SBS, providing new insights into the potential etiologic mechanisms in chronic inflammatory diseases.

Indoor bacterial, fungal and viral species and functional genes in urban and rural schools in Shanxi Province, China-association with asthma, rhinitis and rhinoconjunctivitis in high school students.

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. Video abstract.

Shotgun metagenomics of dust microbiome from flight deck and cabin in civil aviation aircraft.

Microbial exposure is related to the health of passengers on commercial aircraft, but no studies characterized the microbial composition at the species level and identified their ecological determinants. We collected vacuum dust from floor and seat surfaces in flight decks and cabins of 18 aircraft, and amplification-free shotgun metagenomics was conducted to characterize the microbial composition. In total, 7437 microbial taxa were identified. The relative abundance for bacteria, eukaryote, viruses, and archaea was 96.9%, 1.8%, 0.3%, and 0.03%, respectively. The top bacterial species mainly derived from outdoor air and human skin included Sphingomonas, Corynebacterium, Micrococcus luteus, Variovorax paradoxus, Paracoccus dentrificans, and Propionibacterium acnes. The abundance of NIAID-defined pathogens was low, accounted for only 0.23% of total microbes. The microbial species and functional composition were structured by the indoor surface type (R2  = 0.38, Adonis), followed by the manufacturer of the aircraft (R2  = 0.12) and flight duration (R2  = 0.07). Indoor surfaces affected species derived from different habitats; the abundance of dry skin and desiccated species was higher on textile surfaces, whereas the abundance of moist and oily skin species was higher on leather surfaces. The growth rates for most microbes were stopped and almost stopped.