P13. Differences in microbiota and inflammation in a cohort of elite controllers
Piotr Nowak1, Jan Vesterbacka1, Javier Rivera2, Marc Noguera-Julian2, Kajsa Noyan3, Roger Paredes2, Anders Sönnerborg1,3.
Affiliates: 1Department of Medicine Huddinge, Unit of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. 2IrsiCaixa & AIDS Unit, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain. 3Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
The gut microbiota is altered in HIV-1 infected patients and this dysbiosis is associated with immune activation and inflammation. However, little is known on the role of gut microbiota alterations in individuals who naturally can control HIV-1 infection.
We analysed gut microbiota in a cohort of patients with HIV infection (n=48) and HIV negative controls matched by age, gender and sexual orientation (n=16). The HIV cohort included 16 patients defined as elite controllers and 32 patients with untreated progressive HIV infection. Fecal microbiota composition was determined by 16S rRNA sequencing (Illumina, MiSeq). Soluble markers of inflammation (hsCRP, sCD14, hsIL-6, LBP, neopterin) and metabolites of tryptophan catabolism pathway were analysed in plasma by ELISA or HPLC, respectively. Additionally, activation markers on CD4-CD8 T cells (HLA-DR and CD38) were determined by flow cytometry.
Several alpha diversity measures (Observed species, Chao1 and ACE) were significantly higher in elite controllers compared to patients with progressive infection (median CD4 T-cell count 806 vs 390 cells/µL, respectively) and uninfected controls. The microbiota of patients with progressive infection had the lowest richness. Additionally, we observed several differences in the microbiota composition between the groups. At genus level, elite controllers had higher mean abundance of Succinivibrio, Sutterella and Anaerofilum. In contrast, Blautia and Anaerostipes were significantly enriched in patients with progressive infection. Soluble markers of inflammation were not increased in elite controllers as compared to matched healthy controls besides hsCRP (p=0.006). Higher levels of cellular immune activation were observed in patients with progressive infection, and their kynurenine/tryptophan ratio (indicating IDO-1 enzymatic activity) was significantly increased as compared to elite controllers and healthy controls.
Elite controllers show a gut microbiota richness similar to that of healthy controls and significantly higher than untreated HIV infected patients with progressive infection. Additionally, we confirm that the patients with progressive HIV infection have profound microbiome alterations, inflammation and immune activation. The re-shaping of the microbiota may be an interesting strategy as an additional treatment of patients with progressive HIV infection.