Link Between ‘Leaky Gut’ and Immune Dysfunction in HIV-Positive Patients

by Meghan Grandal

Patients with human immunodeficiency virus (HIV) are treated with antiretroviral therapy (ART), which helps the immune system recover but can lead to production of self-destructive autoantibodies. We all produce low levels of autoantibodies, but persistently high levels may cause autoimmunity, as is common in HIV patients.

Wei Jiang, M.D., associate professor in the Department of Microbiology and Immunology at the Medical University of South Carolina (MUSC), researches immune dysfunction in HIV-positive patients. In a recently published article in Microbiome, Jiang and her team report that HIV-positive, ART-treated patients with high levels of autoantibodies also have increased levels of Staphylococcus aureus products in their blood.

The MUSC study compared autoantibody production in HIV-positive and healthy individuals before and after administration of a seasonal flu vaccine. Patients provided blood samples before vaccination and one and two weeks after, and the samples were tested using a 125-autoantibody array panel. The mechanism of autoantibody generation was examined by determining the plasma levels of microbial products, gene expression profiles of B cells and B cell receptor repertoires.

The autoimmune response in the HIV-positive patients was linked to the presence of S. aureus products in the blood. Some people with HIV have a higher baseline level of these bacterial products in their system. The team examined other strains of bacteria but linked only Staphylococcus to autoantibody production.

The increased level of Staphylococcus products may be linked to “leaky gut.” Patients with leaky gut have a compromised intestinal lining, which enables toxic products from the gut microbiota to translocate into the blood and become accessible to the immune system. This persistent immune response may stimulate autoantibody production. A leaky gut is associated with several autoimmune diseases, including irritable bowel syndrome, celiac disease and type 1 diabetes.

To verify their findings, Jiang and her team injected heat-killed Staphylococcus bacteria into healthy mice and found that it did in fact stimulate autoantibody production.

“We are now studying which specific Staphylococcus products are active in autoantibody production in mice,” says Jiang. “It may be possible to design an inhibitor to block these bacteria from activating the immune cells.”