THE HUMAN BODY IS HOME TO A WIDE RANGE OF MICROORGANISMS THAT UNDER NORMAL, HEALTHY CONDITIONS, INHABIT THE GUT, THE SKIN, THE RESPIRATORY TRACT OR THE ORAL CAVITY, AMONG OTHER NICHES. THE APPLICATION OF CULTURE-INDEPENDENT TECHNIQUES LIKE METAGENOMICS OR DIRECT HIGH-THROUGHPUT SEQUENCING HAS ALLOWED RESEARCHERS TO STUDY THE COMPOSITION, ACTIVITY AND CONTRIBUTION OF HUMAN MICROBIOTA UNDER HEALTH AND DISEASE CONDITIONS. OUR GROUP HAS MAINLY FOCUSED ON THE STUDY OF THE ORAL MICROBIOTA, PERFORMING SOME OF THE FIRST ¿OMICS¿ STUDIES IN THIS NICHE WORLDWIDE. OUR RESEARCH, AS WELL AS THE WORK BY OTHER RESEARCH GROUPS, HAS SHOWN THAT THE ORAL MICROBIOTA IS NOT ONLY IMPORTANT FOR KEEPING HOMEOSTASIS IN THE ORAL CAVITY BUT CAN ALSO HAVE AN IMPORTANT INFLUENCE ON OTHER ASPECTS OF OUR GENERAL HEALTH, AND VICE-VERSA. FOR INSTANCE, IMPORTANT LINKS HAVE BEEN FOUND BETWEEN BAD ORAL HEALTH AND DIFFERENT TYPES OF CANCER, AS WELL AS WITH AN INCREASED CARDIOVASCULAR RISK, BACTERIAL ENDOCARDITIS OR PREMATURE BIRTH, AMONG OTHER CONDITIONS. IN THE CURRENT PROPOSAL, WE WANT TO MOVE FROM A DESCRIPTIVE TO A MORE FUNCTIONAL APPROACH, IN WHICH WE FOCUS ON THE LOCAL (I.E. AFFECTING ORAL HEALTH) AND SYSTEMIC (I.E. AFFECTING SYSTEMIC HEALTH) EFFECTS OF THE ORAL MICROBIOTA, AS WELL AS ITS INTERACTIONS, IN WHAT WE COULD CALL THE ¿ORAL-SYSTEMIC AXIS¿. THE PROJECT WILL BE STRUCTURED IN TWO WORKPACKAGES. IN THE FIRST ONE WE WILL FOCUS ON STUDYING THE ROLE OF NITRATE-REDUCING ORAL BACTERIA FOR PREVENTING DENTAL CARIES AND PERIODONTAL DISEASE, AND THEIR EFFECT ON CARDIOVASCULAR HEALTH. WE WILL USE THE NITRATE REDUCING CAPACITY (NRC) TEST DEVELOPED IN THE PREVIOUS FUNDED PROJECT OF OUR GROUP TO COMPARE THE NRC IN 1) INDIVIDUALS WITH/WITHOUT DENTAL CARIES; 2) INDIVIDUALS WITH/WITHOUT PERIODONTITIS; 3) INDIVIDUALS BEFORE AND AFTER PERIODONTAL TREATMENT; AND 4) INDIVIDUALS TAKING A NITRATE SUPPLEMENT. IN ADDITION, WE WILL STUDY THE RELATIONSHIP BETWEEN NRC AND BLOOD PRESSURE AND PHYSICAL PERFORMANCE. IN THE SECOND WORKPACKAGE, WE WILL STUDY THE POTENTIAL LINK BETWEEN ORAL MICROBIOTA AND COLORECTAL CANCER (CRC), A DISEASE THAT HAS BEEN PROPOSED TO BE DIRECTLY INFLUENCED BY SPECIFIC MICROORGANISMS, MAINLY THE TYPICAL ORAL INHABITANT FUSOBACTERIUM NUCLEATUM. THUS, WE WILL COMPARE THE MICROBIOTA OF ORAL SAMPLES AND TUMOR TISSUE IN PATIENTS WITH CRC, IN ORDER TO IDENTIFY IF THE ORIGIN OF THE TUMOR-ASSOCIATED BACTERIA IS THE ORAL CAVITY. IN ADDITION, WE WILL PERFORM A METATRANSCRIPTOMIC ANALYSIS OF THE AFFECTED TISSUE, IN ORDER TO EXPLORE THE EXPRESSION PATTERN OF THE MICROBIAL COMMUNITY, WHICH COULD LEAD TO A BETTER UNDERSTANDING OF THE PROCESSES LEADING TO TUMORIGENESIS AND CANCER PROGRESSION. THUS, THE CURRENT PROJECT WILL UNRAVEL THE CONTRIBUTION OF ORAL MICROBIOTA TO IMPORTANT ASPECTS OF LOCAL AND SYSTEMIC HEALTH, WHICH WILL ALLOW US TO DEVELOP SEVERAL PRODUCTS AND DIAGNOSTIC TESTS WITH DIRECT PRACTICAL APPLICATIONS.