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

Indoor microbial exposure is associated with asthma, but the health effects of indoor metabolites and chemicals are not comprehensively assessed. Here, we collected classroom dust from 24 junior high schools in three geographically distanced areas in Malaysia, including Johor Bahru, Terengganu, and Penang, and conducted culture-independent high-throughput microbiome and untargeted metabolomics/chemical profilings. 1290 students were surveyed for asthma symptoms (wheeze). In each center, we found significant variation in the prevalence of wheeze among schools, which cannot be explained by personal characteristics and air pollutants. Large-scale microbial variations were observed between three centers; the potential protective bacteria were mainly from phylum Actinobacteria in Johor Bahru, Cyanobacteria in Terengganu, and Proteobacteria in Penang. In total, 2633 metabolites and chemicals were characterized. 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 pesticide (2(3H)-benzothiazolethione), fragrance (2-aminobenzoic acid, isovaleric acid), detergent and plastic (phthalic acid), and industrial material (4,4-sulfonyldiphenol). This is the first association study between high-throughput indoor chemical profiling and asthma symptoms. The consistent results from three centers indicate that indoor metabolites/chemicals could be a better indicator than indoor microbiome for environmental and health assessments, providing new insights for asthma prediction, prevention, and control.