Intestinal Tract

The gastrointestinal tract is a home for complex community of commensal bacterial species. This gut microbial community also known as microbiota has co-evolved with its host over millennia and provides benefits to its host in many ways such as digestion, detoxification, production of nutrients, protection against pathogens and regulation of immune system. Immune system plays important role in maintaining the body healthy health by elimination of pathogens.

CD4+ T cells in particular, play key role in the adaptive immune system and located in the lamina propria (LP) of the intestine. Microbiota plays important role in the development of CD4+ T cells. Stimulated naive CD4+ T cells can differentiate into T helper 1 (Th1), Th2 and Th17. Altered

Available literature suggests that alterations in normal microbial community of several organ systems can further influence HIV transmission, progression and the potential for a vaccine or cure. Despite effective viral suppression with antiretroviral therapy (ART), individuals with HIV continue to have excess non-AIDS morbidity and mortality. Much work has gone into elucidating the mechanisms by which intestinal microbiota augment or disrupt intestinal barrier function, immune response to antigen and systemic immune

A recent study led by Dhillon and colleagues studied the potential mechanisms by which altered intestinal microbiota contribute to HIV-1-associated mucosal pathogenesis. This group utilized the Lamina Propria Aggregate Culture (LPAC) model to investigate the impact of HAMB species (HIV-altered mucosal bacteria) on LP CD4 T cell infection and depletion in vitro. Their study provided the evidence that commensal bacteria that are altered in the colonic mucosa of HIV-1 infected individuals enhance infection and depletion of LP CD4 T cells by HIV co-receptor CCR5-tropic HIV-1. Further they found that gram-negative HAMB appeared to enhance infection and depletion of LP CD4 T cells than gram-positive HAMB. Unexpectedly, HAMB that induced productive infection and CD4 T cell death facilitated only a minimal increased LP T cell activation. However, these same bacteria induced considerable increases in CCR5 expression on LP CD4 T cells. CCR5 over expression by HAMB mediated by indirect stimulation of LP CD4 T cells and likely mediated through LPS signaling. These observations highlight that bacteria may utilize diverse mechanisms to contribute to HIV associated pathogenesis.

Considering the significance of gut microbiota imbalance, recognizing how microbiome dynamics impacts HIV infection leading to death of intestinal