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Asthma prevalence has increased in epidemic proportions with urbanization, but growing up on traditional farms offers protection even today. 1 The asthma-protective effect in farms appears to be associated with rich home dust microbiota, 2,3 which could be used to model a health-promoting indoor microbiome. Here we show by modelling differences in house dust microbiota composition between farm and non-farm homes of Finnish birth cohorts 4 that in children who grow up in non-farm homes asthma risk decreases as the similarity of their home bacterial microbiota composition to that of farm homes increases. The protective microbiota had a low abundance of Streptococcaceae relative to outdoor-associated bacterial taxa. The protective effect was independent of richness and total bacterial load and was associated with reduced proinflammatory cytokine responses against bacterial cell wall components ex vivo. We were able to reproduce these findings in a study among rural German children 2 and showed that children living in German non-farm homes with an indoor microbiota more similar to Finnish farm homes have decreased asthma risk. The indoor dust microbiota composition appears as a definable, reproducible predictor of asthma risk and a potential modifiable target for asthma prevention. MAIN TEXTFrom ancient times, humans have adapted to rich microbial exposures in early life. Changes in these exposures in modern urbanized environments may drive the epidemic increases in asthma and allergies. 5,6 Many studies describe and identify protective microbial exposures but with heterogeneity in the specific microbial signals. Thus microbial exposures that could be exploited for preventive interventions remain unidentified. Here, we tested whether it is possible to circumvent this issue with an anchor-based method, drawing on the well-characterized asthma-protective effect of growing up on animal farms that appears associated with their particular indoor dust microbiota composition. 2,3 If the indoor microbiota in farm homes causally protects from asthma, as suggested by experimental data, 3,7,8 similar microbiota in non-farm homes should also have a protective effect despite the different surrounding environment and life-style.We characterized the indoor microbiota from living-room floor dust collected from the homes of Finnish birth cohorts, LUKAS1 and LUKAS2, 4,9 at the index child age of 2 months. At this age infants who crawl are constantly exposed to floor dust via the respiratory tract, skin and mouth. 10,11 The characteristics of the farm home microbiota were defined within LUKAS1, which includes only