Published online Feb 14, 2022. doi: 10.3748/wjg.v28.i6.635
Peer-review started: May 28, 2021
First decision: June 30, 2021
Revised: July 30, 2021
Accepted: January 13, 2022
Article in press: January 13, 2022
Published online: February 14, 2022
Processing time: 256 Days and 16.9 Hours
Human immunodeficiency virus type 1 (HIV-1) infection is characterized by persistent systemic inflammation and immune activation, even in patients receiving effective antiretroviral therapy (ART). Converging data suggest that gut microbiota (GM) changes can occur throughout including human immunodeficiency virus (HIV) infection treated by ART.
ART has increased the life expectancy of HIV-infected patients; however, chronic inflammation and gut microbiota alterations persist in patients virologically suppressed by ART. These data suggest that re-shaping the microbiota may be an adjuvant therapy in patients commencing successful ART.
The purpose of this prospective observational study was to compare for the first time the fecal microbial composition, serum and fecal microbial metabolites, and serum cytokine profile of treatment-naïve patients before starting ART and after reaching virological suppression (HIV RNA < 50 copies/mL) after 24 wk of ART.
The authors enrolled 12 treatment-naïve HIV-infected patients receiving ART. Fecal microbiota composition was assessed through next generation sequencing, and a comprehensive analysis of a broad spectrum of cytokines in blood was performed through a multiplex approach. In addition, serum free fatty acid (FFA) and fecal short chain fatty acid (SCFA) levels were measured through GC-MS.
The authors compared microbiota signatures, FFA levels, and cytokine profile before starting ART and after reaching virological suppression. Modest alterations were observed on microbiota composition; moreover, in the same condition, we also observed augmented levels of serum propionic and butyric acids. A reduction of serum IP-10 and an increase of IL-8 level were detected in the viral suppression condition. Thereafter, the same components were compared between immunological responders and non-responders. Concerning the microflora population, we detected a reduction of Faecalibacterium and an increase of Alistipes in immunological non-responders. Simultaneously, fecal isobutyric, isovaleric, and 2-methylbutyric acids were also increased in immunological non-responders.
The results provid an additional perspective about the impact of HIV infection, ART, and immune recovery on the “microbiome-immunity axis” at the metabolism level. These factors can act as indicators of the active processes occurring in the gastrointestinal tract.
Future larger-scale, long-term ART and longitudinal studies that include functional metagenomic and metabolomic approaches to identify the roles of the specific differential phylotypes are required to better define the relationship between microbiota-immunity axis and HIV-1 infection and to provide new insights into the targeted treatment, improving the immune recovery and dampening inflammation.