UC San Diego

The human gut microbiome plays an essential role in the maturation and maintenance of the gut associated lymphoid tissue (GALT), yet how the composition of this microbiome assists in this function is not completely understood. Most previous gut flora studies have been limited since they required the isolation and cultivation of microbes, and many of the gut microbes cannot be cultured. The advent of next generation sequencing has improved the identification of the composition of the human gut microbiome, but these techniques require better methods for analyzing these high dimensional data. To overcome these bioinformatics challenges, a pipeline was developed and applied for the study of the gut microbiome during Human Immunodeficiency Virus (HIV) infection. The hallmark of HIV infection is the depletion of CD4 T cells, particularly in the gastrointestinal (GI) tract. This depletion compromises gut integrity and results in the translocation of microbial products into the bloodstream. Using next generation sequencing, we found that during untreated HIV infection, gut bacterial profiles segregated 11 participants according to their systemic lymphocyte percentages (Group 1 : median CD4% = 9.5% vs. Group 2 : median CD4% = 33%). Additionally, regression analyses showed that Lactobacillales in the distal gut were associated with higher CD4 counts and CD4%, less immune activation, less viral replication, less gut T cell proliferation and less microbial translocation in untreated and treated HIV infection. Changes of gut bacterial populations may reflect gut immune health and therefore interventions targeted to gut microbiota might help rebuild gut integrity during HIV infection