Effect of the Microbiome/Virome on Mucosal and Systemic Inflammation in Health and Disease

We study the bacterial and viral microbiome at mucosal surfaces to determine how these organisms contribute to inflammation and disease states. The human microbiome consists of bacteria and archaea, viruses and bacteriophage, fungi, protists, and other microbial eukaryotes. Composition of the microbiota varies by body site and is unique between individuals. The relatively low sequencing cost associated with 16S rRNA genomics and publically available tools for demultiplexing, quality control, bacterial sequence identification has facilitated bacteriome exploration. Research into the virome has been hampered by lack of a common genetic element to enable a “pan-virus” PCR and difficulty culturing many viruses. Next generation sequencing has revolutionized the study of this important microbial compartment. Using next-generation sequencing, molecular biology techniques and bioinformatics analysis we are exploring the contributions of the human microbiome and virome on health and disease.

One of the focuses of our laboratory is HIV (Human Immunodeficiency virus). HIV constitutes a serious public health problem with an estimated 1.1 million adults infected in the United States alone, and approximately 50,000 new infections annually. HIV enters through mucosal membranes and rapidly targets the CD4+ T cell population, leading to disruption of immune homeostasis, induction of inflammatory cytokines and chemokines, and eventually if untreated the development of opportunistic infections and death. Antiretroviral therapy (ART) successfully controls replicating virus populations, but immune recovery is variable making preventative or curative strategies imperative. We have previously shown that immunodeficiency from HIV infection is associated with alterations in enteric bacterial diversity and expansion of potentially pathogenic enteric bacteria and viruses. Treatment of mucosal pathogens, in conjunction with ART, may minimize HIV-associated chronic immune activation and decrease morbidity and mortality in persons living with HIV.