To construct a saliva-based caries risk assessment model, saliva samples from 176 severe early childhood caries (S-ECC) children and 178 healthy (H) children were screened by real-time PCR-based quantification of the selected species, including Streptococcus mutans, Prevotella pallens, Prevotella denticola and Lactobacillus fermentum. Host factors including caries status, dmft indices, age, gender, and geographic origin were assessed in their influence on abundance of the targeted species, which revealed host caries status as the dominant factor, followed by dmft indices (both P < 0.01). Moreover, levels of S. mutans and P. denticola in the S-ECC group were significantly higher than those in the healthy group (P < 0.001 for S. mutans and p < 0.01 for P. denticola). Interestingly, the co-occurrence network of these targeted species in the S-ECC group differed from that from the healthy group. Finally, based on the combined change pattern of S. mutans and P. pallens, we constructed an S-ECC diagnosis model with an accuracy of 72%. This saliva-based caries diagnosis model is of potential value for circumstances where sampling dental plague is difficult. Early childhood caries (ECC) is defined as the presence of one or more decayed, missing, or filled tooth surfaces in the primary dentition in children of 71 months or younger 1. Severe early childhood caries (S-ECC), an extraordinary form of ECC, is defined as the presence of decayed, missing, or filled score surfaces of either ≥4 (age 3 years), ≥5 (age 4 years), or ≥6 (age 5 years) 2. In USA, 23% of children between the ages of 2 and 5 are affected by ECC 3. In China, fresh reports from the Fourth National Oral Health Survey showed that over 70% of 5-year-old children carry dental caries in primary teeth 4. Unfortunately, childhood caries are wide-ranging, rapid-progressing and irreversible 5. Besides, severe caries can cause pulpal infection, as well as varieties of adverse physical and psychological effects, thus it affects children's development while posing a substantial economic burden on both families and society 6-8. Therefore, preventive measures and early diagnosis of ECC or S-ECC are of vital clinical and social importance. Many studies have shown that caries is a multifactorial disease 9,10 and pathogenic bacteria are the main cause of disease occurrence and progression 11. Streptococcus mutans (S. mutans) has been considered as a cariogenic bacterial agent in children 12-15 , due to its aciduric and acidogenic properties 16. Apart from this, Lactobacillus spp. was also linked to caries development and progression 16-18. Positive associations between certain Lactobacillus spp. (especially Lactobacillus fermentum) and the hard tissue changes were revealed in the process of caries progression 19,20. In addition, our past pyrosequencing of oral and plaque microbiota unveiled Prevotella spp's close relationship with caries, in both cross-sectional and longitudinal studies 21,22. Specifically, we proposed a caries