Periodontitis is the most common infectious disease of man. It can finally lead to tooth loss and is a risk factor for chronic rheumatoid arthritis, heart failure and other systemic diseases. Studying the metatranscriptome of periodontal pockets unveils for the first time what the microbes are doing in vivo, i.e. in their human host in the presence of several hundreds of other microbial taxa. This approach allows testing hypotheses in great detail, especially with regard to the response of so-called commensals. For example, our analysis of a small cohort of individuals with chronic periodontitis showed that not only Fusobacterium nucleatum but additional taxa and additional pathways contributed to butyric acid synthesis in periodontitis, or that Prevotella nigrescens turned pathogenic in dysbiosis. The PAD enzyme from Porphyromonas gingivalis which is causally related to an autoimmune type of rheumatoid arthritis was highly expressed, and unexpectedly, a homologue was found in a mycobacterium species. When analyzing the corresponding human transcriptomes in periodontal pockets we found evidence for competition for iron as well as differentially expressed cancer related genes. The data provide evidence on the level of gene expression in vivo for the potentially severe impact of the dysbiotic microbiota on human health.