Gut microbiota diversity predicts immune status in HIV-1 infection.
OBJECTIVE
HIV-1 infection is characterized by altered intestinal barrier, gut microbiota dysbiosis, and systemic inflammation. We hypothesized that changes of the gut microbiota predict immune dysfunction and HIV-1 progression, and that antiretroviral therapy (ART) partially restores the microbiota composition.


METHODS
An observational study including 28 viremic patients, three elite controllers, and nine uninfected controls. Blood and stool samples were collected at baseline and for 19 individuals at follow-up (median 10 months) during ART.


METHODS
Microbiota composition was determined by 16S rRNA sequencing (Illumina MiSeq). Soluble markers of microbial translocation and monocyte activation were analyzed by Limulus Amebocyte Lysate assay or ELISA.


RESULTS
Several alpha-diversity measures, including number of observed bacterial species and Shannon index, were significantly lower in viremic patients compared to controls. The alpha diversity correlated with CD4 T-cell counts and inversely with markers of microbial translocation and monocyte activation. In multivariate linear regression, for every age and sex-adjusted increase in the number of bacterial species, the CD4 T-cell count increased with 0.88 (95% confidence interval 0.35-1.41) cells/μl (P = 0.002). After introduction of ART, microbiota alterations persisted with further reduction in alpha diversity. The microbiota composition at the genus level was profoundly altered in viremic patients, both at baseline and after ART, with Prevotella reduced during ART (P < 0.007).


CONCLUSIONS
Gut microbiota alterations are closely associated with immune dysfunction in HIV-1 patients, and these changes persist during short-term ART. Our data implicate that re-shaping the microbiota may be an adjuvant therapy in patients commencing successful ART.
aDepartment of Medicine Huddinge, Unit of Infectious Diseases, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden bDepartment of Infectious Diseases, Oslo University Hospital, Ullevål Hospital cK.G. Jebsen Centre for Inflammation Research, University of Oslo, Oslo dNorwegian University of Life Sciences, Ås, Norway eDepartment of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden fNorwegian PSC Research Centre, Dept of Transplantation Medicine and Section of Gastroenterology gResearch Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Oslo, Norway.
Piotr
P
Nowak
Marius
M
Troseid
Ekatarina
E
Avershina
Babilonia
B
Barqasho
Ujjwal
U
Neogi
Kristian
K
Holm
Johannes R
JR
Hov
Kajsa
K
Noyan
Jan
J
Vesterbacka
Jenny
J
Svärd
Knut
K
Rudi
Anders
A
Sönnerborg
D000328:Adult; D000368:Aged; D018988:Bacterial Translocation; D015331:Cohort Studies; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004275:DNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D064806:Dysbiosis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000069196:Gastrointestinal Microbiome; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D008033:Limulus Test; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D008969:Molecular Sequence Data; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA; D055815:Young Adult
D004269:DNA, Bacterial; D004275:DNA, Ribosomal; D012336:RNA, Ribosomal, 16S