AI Article Synopsis
- HIV infection leads to gastrointestinal mucosal damage, which affects microbial balance and immune response, leading to non-infectious comorbidities in people living with HIV (PLWH).
- A study measured zonulin levels in serum and intestinal tissue from HIV-infected individuals and controls, revealing higher levels of zonulin in the bloodstream of HIV patients, but lower levels in their gut tissue compared to controls.
- Elevated systemic zonulin was linked to the loss of intestinal CD4 T cells and increased gut inflammation, suggesting a relationship between zonulin and intestinal health that could be important for managing comorbidities in PLWH.
Article Abstract
Background: Gastrointestinal mucosal damage due to human immunodeficiency virus (HIV) infection leads to microbial translocation and immune activation, contributing to the development of non-infectious comorbidities (NICM) in people living with HIV (PLWH). Additionally, persistent proviral HIV-1 in the gut-associated lymphatic tissue (GALT) can trigger immunological changes in the epithelial environment, impacting the mucosal barrier. However, the role of zonulin, a modulator of epithelial tight junctions in GALT during HIV infection, remains poorly understood.
Methods: We measured zonulin in serum and intestinal tissue sections from five treatment-naive (HIV) and 10 cART-treated (HIV) HIV individuals, along with 11 controls (CTRL). We compared zonulin levels with clinical characteristics, inflammatory markers (IFN-α, CXCR3, and PD-1), and the viral reservoir in peripheral blood (PB) and terminal ileum (TI).
Results: Upon HIV infection, TI was found to harbor more HIV DNA than PB. Circulating zonulin levels were highest in HIV compared to HIV or CTRL. Surprisingly, in the gut tissue sections, zonulin levels were higher in CTRL than in HIV individuals. Elevated circulating zonulin levels were found to be correlated with CD4T-cell depletion in PB and TI, and with intestinal IFN-α.
Conclusions: The findings of this study indicate a shift in zonulin levels from the gut to the bloodstream in response to HIV infection. Furthermore, elevated systemic zonulin levels are associated with the depletion of intestinal CD4 T cells and increased gut inflammation, suggesting a potential link between systemic zonulin and intestinal damage. Gaining insight into the regulation of gut tight junctions during HIV infection could offer valuable understanding for preventing NICM in PLWH.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505231 | PMC |
| http://dx.doi.org/10.3390/biomedicines12102316 | DOI Listing |
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