Mammals are home to a commensal microbial community referred to as the microbiota. Recent data has provided compelling evidence that microbial residents on mammals are crucial for proper development and health. Indeed, changes in intestinal microbial communities have been associated with inflammatory bowel disease (IBD), diabetes, allergies, obesity, multiple sclerosis and even autism. Recent research, including our own, has demonstrated that replacement of beneficial bacterial species or deletion of pathogenic microbes can protect and even cure diseases in animal model systems. While the presence of beneficial bacteria can prevent or cure disease the loss of these bacteria or the outgrowth of particular 'bad'commensal bacteria can induce disease. Therefore, it appears that maintaining the proper balance, or community structure, of commensal organisms is critical to health. This highlights the critical need to develop methodologies that allow for therapeutic manipulation of the microbiota. Current methodologies such as antibiotics or anti-microbials target large groups of bacteria and do not provide a sufficient level of specificity. Indeed, antibiotic use to clear a pathogen is well known to disrupt beneficial commensal communities, leading to permanent loss of particular members of the microbiota and creating niches for pathogens, a process referred to as dysbiosis. Moreover, greater antibiotic use has been correlated with increasing incidence of autoimmunity, likely because of disruptions to the beneficial organisms that we harbor. Thus, novel therapies to control bacterial populations and target specific organisms is sorely needed. This proposal will set forth experiments to better understand a numerically prominent member of our microbiota, our virobiota as a means to develop novel therapeutic strategies to manipulate health microbial communities. While the microbiota outnumbers our own cells by an order of magnitude, the virobiota is mainly composed of bacteriophages that outnumber the microbiota by estimated factor of 10. This means that bacteriophages represent one of the most abundant forms of foreign material on our bodies. While bacteriophages solely prey on bacteria as their hosts, an abundance of free phage has been found in both human and mouse mucus secretions, suggesting that phage has the capacity to influence immune system development on its own. Therefore, these studies have the potential to lay the foundation for the identification of novel ways to selectively get ri of pathogenic members of the microbiota that induce disease and exploring how these tiny bacterial predators may have shaped human evolution and health.
It has recently been demonstrated that the commensal bacteria that reside on our bodies are instrumental for proper development and health. Indeed, disruptions in the composition of the microbial community are correlated with disease. This underscores the importance of understanding the host pathways that are relevant for shaping microbial communities. Our studies are focused on uncovering novel therapies to get rid of bad microbes without damaging the beneficial communities that reside on our bodies.
|Kubinak, Jason L; Petersen, Charisse; Stephens, W Zac et al. (2015) MyD88 signaling in T cells directs IgA-mediated control of the microbiota to promote health. Cell Host Microbe 17:153-63|
|Kubinak, Jason L; Stephens, W Zac; Soto, Ray et al. (2015) MHC variation sculpts individualized microbial communities that control susceptibility to enteric infection. Nat Commun 6:8642|