Antimicrobial resistance (AMR) is projected to be the cause of >10 million deaths annually by 2050. While efforts to find new potent antibiotics are effective, they are expensive and outpaced by the rate at which new resistant strains emerge.

Background: Juvenile dermatomyositis (JDM) is a rare immune-mediated disease of childhood that is thought to result from genetic predisposition and environmental drivers, with documented links to microbial exposures. In this multi-center, prospective, observational cohort study, we evaluated whether JDM is associated with discrete oral and gut microbiome signatures.Methods: We generated 16S rRNA sequencing data from fecal, saliva, supragingival, and subgingival plaque samples from JDM probands (n=28, age range 3-18 years, mean age 10 years, 46% female). To control for genetic and environmental determinants of microbiome community structure to the greatest extent possible, we also profiled microbiomes of their unaffected family members (n=27 siblings, n=26 mothers, and n=17 fathers). We performed paired within-family comparisons as well as unpaired analyses of different cohorts. Results: Sample type (oral vs fecal) and nuclear family unit were the two most predominant variables explaining variance in microbiome diversity, more so than having a diagnosis of JDM. The oral and gut microbiomes of JDM probands were more similar to their own unaffected siblings than they were to the microbiomes of other JDM probands. Nonetheless, in a sibling-paired analysis, several potentially immunomodulatory bacterial taxa were differentially abundant in the microbiomes of JDM probands compared to their unaffected siblings, including Faecalibacterium in the gut and Streptococcus in the oral cavity. Further, compared to published microbiome datasets generated from healthy children and adults, fecal microbiomes of both JDM probands and their unaffected family members were markedly different. Conclusions: Family unit (which reflects the confluence of genetic and household effects) has a significant effect on microbiome community structure. Features of the dysbioses seen in oral and fecal microbiomes of JDM probands were shared by their unaffected family members, suggesting familial microbiome signatures. The loss or gain of specific fecal and oral bacteria may potentially play a role in disease pathogenesis and/or be secondary to immune dysfunction in susceptible individuals.