title: Reduced Levels of D-dimer and Changes in Gut Microbiota Composition After Probiotic Intervention in HIV-Infected Individuals on Stable ART.
abstract: BACKGROUND
  Microbial translocation and chronic inflammation may contribute to non-AIDS morbidity in patients with HIV. This study assessed the impact of probiotic intervention on microbial translocation and inflammation in patients on antiretroviral therapy with viral suppression and subnormal CD4 count.
  
  
  METHODS
  Thirty-two patients receiving antiretroviral therapy (CD4 <500 cells/μL) were randomized in a double-blind fashion to multistrain daily probiotics (n = 15), placebo (n = 9), or controls (n = 8) for 8 weeks. Soluble inflammation markers, D-dimer, lipopolysaccharide (LPS), sCD14, T-cell activation, tryptophan metabolites, and gut microbiota composition were analyzed at baseline and end of study. Nonparametric statistics were applied.
  
  
  RESULTS
  Twenty-four participants completed the study and were included in as-treated analyses. In patients receiving probiotics, there was a significant reduction in D-dimer levels (median change 33%, P = 0.03) and a tendency to reduced levels of C-reactive protein (CRP) (P = 0.05) and interleukin (IL)-6 (P = 0.06). The changes in CRP and IL-6 were highly correlated (r = 0.95, P < 0.01), whereas changes in D-dimer did not correlate with changes in CRP or IL-6. Increases in Bifidobacteria (P = 0.04) and Lactobacilli (P = 0.06) were observed in the probiotic group, whereas the relative abundance of Bacteroides decreased (P ≤ 0.01). No significant changes were seen in markers of microbial translocation or T-cell activation. However, the expansion of Bifidobacteria correlated negatively with differences in LPS (r = -0.77, P = 0.01), whereas the reduction in Bacteroides correlated positively with changes in LPS during the study period (r = 0.72, P = 0.02).
  
  
  CONCLUSIONS
  Probiotic intervention seemed to reduce markers of coagulation and inflammation without overt changes in microbial translocation. These findings warrant further studies in larger cohorts with long-term follow-up.
authors.affiliation: *Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway; †Department of Infectious Diseases, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; ‡Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; §Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences; ‖K.G. Jebsen Center for Inflammation Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; ¶Department of Clinical Science, University of Bergen, Bergen, Norway; #Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway; **Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway; ††TINE SA, TINE R&D, Oslo, Norway; ‡‡Department of Haematology, Akershus University Hospital, Nordbyhagen, Norway; §§Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Oslo, Norway; ‖‖Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway; and ¶¶Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Oslo, Norway.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Stiksrud
authors.forename: Piotr
authors.initials: P
authors.lastname: Nowak
authors.forename: Felix C
authors.initials: FC
authors.lastname: Nwosu
authors.forename: Dag
authors.initials: D
authors.lastname: Kvale
authors.forename: Anders
authors.initials: A
authors.lastname: Thalme
authors.forename: Anders
authors.initials: A
authors.lastname: Sonnerborg
authors.forename: Per M
authors.initials: PM
authors.lastname: Ueland
authors.forename: Kristian
authors.initials: K
authors.lastname: Holm
authors.forename: Stein-Erik
authors.initials: SE
authors.lastname: Birkeland
authors.forename: Anders E A
authors.initials: AE
authors.lastname: Dahm
authors.forename: Per M
authors.initials: PM
authors.lastname: Sandset
authors.forename: Knut
authors.initials: K
authors.lastname: Rudi
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Hov
authors.forename: Anne M
authors.initials: AM
authors.lastname: Dyrhol-Riise
authors.forename: Marius
authors.initials: M
authors.lastname: Trøseid
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018988:Bacterial Translocation; D058448:Biota; D004311:Double-Blind Method; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D000069196:Gastrointestinal Microbiome; D015658:HIV Infections / Q000628:therapy*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008070:Lipopolysaccharides / Q000097:blood; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D019936:Probiotics / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D044966:Anti-Retroviral Agents; D005338:Fibrin Fibrinogen Degradation Products; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D010919:Placebos; C036309:fibrin fragment D