It is now accepted that levels and diversity of bacteria present in tissues influence disease progression, and numerous studies have characterized the microbiome in a variety of neurological diseases and conditions and identified differences between patients and healthy controls; specific species that produce metabolites that influence disease; and shown that modifying the microbiome can alter the course of disease. The majority of these studies, including in MS patients, examined the gut microbiome using fecal samples as a surrogate for intestinal flora. However, the microbiome of the oral cavity has a similar high degree of bacterial diversity, and is beginning to be used more often as an easier source of samples. In preliminary studies we analyzed saliva DNA from a pair of monozygotic twins discordant for MS (RRMS versus CIS), and found differences at all taxonomic levels, with species differences greater than 30-fold. In new studies with collaborators in France, we compared the oral biome of 12 MS patients to 24 healthy controls, and found differences at the phylum and genus levels. We now propose to replicate those studies in larger cohorts of MS patients using samples obtained from African American and White Veterans with MS; and compare their oral biome to that of race, gender and age matched controls. The biome will be determined by standard 16S rRNA amplicon sequencing, and comparisons made using available software. We will test if differences in relative abundance can distinguish between MS and controls, and if differences are present in both AA and White MS patients. We will stratify the data to determine if relative abundances are associated with age, gender, or ethnicity. We will also measure levels of bacteria that produce butyrate, a powerful anti-inflammatory molecule, which has been shown to be reduced in MS gut studies. Overall, a knowledge of the oral microbiome will help guide therapeutic approaches designed to increase levels of beneficial species, while reducing levels of potentially detrimental bacteria; and can potentially be used to monitor disease progression and treatment efficacy; and could provide clues as to the contributing causes