The gut microbiome following acute HIV-1 infection
To our knowledge, this is the most comprehensive prospective study investigating the longitudinal impact of acute HIV-1 infection in an HIV-1 hyperendemic area such as the Manhiça district in Mozambique. This unique study confirms and extends previous findings in non-human primate models and provides critical insights into the impact of infections in the gut microbiome as well as into the pathogenesis of HIV-1 infection.
The gut associated lymphoid tissue (GALT) is rapidly and severely damaged upon HIV-1 infection. The extreme damage to the GALT leads the leaky gut phenomenon, where bacterial cells and products usually contained within the gut lumen can now translocate the gut epithelia and enter the lamina propria, thus initiating immune activation and inflammation.
Hence, it is crucial to understand the changes occurring in the gut mucosa as well as in the gut microbiota following first stages of HIV-1 infection. Once we are able to identify them and understand the host-microbiota interplay, we may be able to design new therapeutic approaches to help ameliorate the immune deterioration linked to HIV-1 infection by modulating the gut microbiome.
A major strength in our work is prospectively following-up people from Mozambique after acute HIV-1 infection for up to one year and a half. This longitudinal studies in the developed countries are basically restricted to non-human primate models since acute infections are very difficult to diagnose. First fecal sample from our recently HIV-1 infected individuals (RHI) was collected within the first 1-2 months after viral infection and subsequent fecal and blood samples were periodically collected. Remarkably, we were also able to compare changes in the gut microbiota occurring within the first 18 months to two groups of chronically HIV-1 infected subjects, either on active antiretroviral treatment (ART) or ART-naïve, and HIV-1 negative individuals, thus conforming a huge and clinically relevant cohort.
Surprisingly, longitudinal analysis reported significant increases in microbial richness and diversity in RHI subjects. Deeper analyses including clinical data showed significant decreases in HIV-1 viral load and in CD8+ T-cell counts for the first 6 months of follow-up. Interestingly, this observation led us to hypothesize whether the gut microbiota experiences some transient recovery after an initial negative impact (i.e. implying reduction in ecological markers) that mirror the partial recovery of CD4+T cells after initial peak of viremia (see figure below). If true, this would suggest that to understand the acute effect of HIV-1 infection on the gut microbiota, it is crucial to test the first days, at most the first weeks, after viral entry, and that collecting samples at month 1 might be already too late to see the negative impact on the gut microbiota following HIV-1 infection.
Interestingly we also saw a potential role of eukaryotic viruses related to HIV-1 pathogenesis with significant increased fecal shedding of Adenovirus, Enterovirus and Cytomegalovirus in HIV-1 infected groups. Remarkably, Adenovirus shedding was already increased in RHI and maintained in chronically HIV-1 infected groups regardless of ART, compared to HIV-1 negative controls. These observations reinforce the idea that analyses of the gut microbiome should expand beyond bacteria and understanding the inter and intra-dynamics within the gut microbiota during the first month after HIV-1 infection is strongly needed.
More information: https://rdcu.be/bCk58