The life expectancy of a person living with HIV is approaching that of the general, seronegative population. However, changes to the bacterial environment of the intestinal tract combined with age-associated noncommunicable diseases can lead to chronic inflammation and higher rates of death.
The life expectancy of persons living with HIV (PWH) is approaching that of the general, seronegative population. However, changes to the gut microbiota—the bacterial environment of the intestinal tract—combined with age-associated noncommunicable diseases, can lead to chronic inflammation and higher rates of death.
The influence of gut microbiota in HIV-positive individuals is a rapidly expanding field of study; this is partly due to advancements in antiretroviral therapy (ART) that have increased the life expectancy of a person living with HIV.
“Loss of gut mucosal integrity and an aberrant gut microbiota are proposed mechanisms contributing to chronic inflammation and increased morbidity and mortality during antiretroviral-treated HIV disease,” noted the authors of a recent study in Nature Communications. “Several components of the gut immune barrier that are responsible for regulating composition of the gut microbiota are abnormal in HIV infection.”
To more closely examine how influential bacterial alterations, also known as dysbiosis, in the gut microbiota are in PWH, compared with an HIV-negative population, they extracted data from agehIV study on persons who had HIV (n = 80) and were on ART and on those who did not have HIV (n = 80), matching them for age, body-mass index, sex, and sexual practice. The authors then profiled fecal samples via 16 rRNA sequencing to determine the microbial communities.
Their results showed changes in the levels of good and harmful bacteria. There were elevated levels of bacteria from the Desulfovibrionaceae (specifically, Bilophila wadworthia) and Enterobacteriaceae families in the guts of the HIV cohort, a finding that has previously been associated inflammatory bowel disease. On the other hand, there were decreased levels of homeostasis-promoting, or good, bacteria comprising Clostridiales members of the Lachnospiraceae and Ruminococcaceaet families. These bacteria are associated with providing energy to epithelial cells and inducing differentiation of T regulatory cells.
Both of these findings mirror results from previous studies, supporting the conclusion “that PWH exhibit an altered gut microbiota as compared to HIV-uninfected controls that may include an expansion of pro-inflammatory gut bacteria and a depletion of homeostasis-promoting microbiota members,” the authors noted. This is regardless of sex and sexual practice.
Their findings also illustrate a negative correlation, in that higher levels of bad gut bacteria are associated with the CD4 nadir in PWH, as well as uncorrected CD4 counts prior to initiation of ART. Both are indications of the immune disruption that occurs in light of an untreated infection.
“This impairment of the function of the intestinal epithelium may permit translocation of pro-inflammatory microbiota products into systemic circulation and exacerbate pathological chronic inflammation in treated PWH, providing a putative link between the described HIV-associated microbiota features and noncommunicable, inflammation-associated comorbidities,” the authors concluded.
They suggest further prospective longitudinal studies using larger patient samples. These studies might examine the relationship between gut dysbiosis and host physiology, as well as biopsying the mucosa where disruptive microbial communities are found, which could lead to greater insight into immune system activation in PWH.
Vujkovic-Cvijin I, Sortino O, Verheij E, et al. HIV-associated gut dysbiosis is independent of sexual practice and correlates with noncommunicable diseases. Nat Commun. Published online May 15, 2020. doi:10.1038/s41467-020-16222-8