title: Low abundance of colonic butyrate-producing bacteria in HIV infection is associated with microbial translocation and immune activation.
abstract: Gut microbial translocation is a major driving force behind chronic immune activation during HIV-1 infection. HIV-1-related intestinal dysbiosis, including increases in mucosa-associated pathobionts, may influence microbial translocation and contribute to mucosal and systemic inflammation. Thus, it is critical to understand the mechanisms by which gut microbes and their metabolic products, such as butyrate, influence immune cell function during HIV-1 infection.
  
  
  
  A cross-sectional study was performed to compare the relative abundance of butyrate-producing bacterial (BPB) species in colonic biopsies and stool of untreated, chronic HIV-1-infected (n = 18) and HIV-1-uninfected (n = 14) study participants. The effect of exogenously added butyrate on gut T-cell activation and HIV-1 infection was evaluated using an ex-vivo human intestinal cell culture model.
  
  
  
  Species were identified in 16S ribosomal RNA sequence datasets. Ex-vivo isolated lamina propria mononuclear cells were infected with C-C chemokine receptor type 5-tropic HIV-1Bal, cultured with enteric gram-negative bacteria and a range of butyrate doses, and lamina propria T-cell activation and HIV-1 infection levels measured.
  
  
  
  Relative abundance of total BPB and specifically of Roseburia intestinalis, were lower in colonic mucosa of HIV-1-infected versus HIV-1-uninfected individuals. In HIV-1-infected study participants, R. intestinalis relative abundance inversely correlated with systemic indicators of microbial translocation, immune activation, and vascular inflammation. Exogenous butyrate suppressed enteric gram-negative bacteria-driven lamina propria T-cell activation and HIV-1 infection levels in vitro.
  
  
  
  Reductions in mucosal butyrate from diminished colonic BPB may exacerbate pathobiont-driven gut T-cell activation and HIV replication, thereby contributing to HIV-associated mucosal pathogenesis.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Dillon
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Kibbie
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Kejun
authors.initials: K
authors.lastname: Guo
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Mario L
authors.initials: ML
authors.lastname: Santiago
authors.affiliation: Department of Gastroenterology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Austin
authors.affiliation: Division of Infectious Diseases, University of California, San Diego, La Jolla, California, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Gianella
authors.affiliation: Department of Immunology-Microbiology, Rush University Medical Center, Chicago, Illinois, USA.
authors.forename: Alan L
authors.initials: AL
authors.lastname: Landay
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Donovan
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.|University of Colorado Microbiome Research Consortium, Aurora, Colorado, USA.
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Frank
authors.affiliation: Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Martin D
authors.initials: MD
authors.lastname: McCARTER
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
authors.forename: Cara C
authors.initials: CC
authors.lastname: Wilson
mesh_terms: D000328:Adult; D001419:Bacteria / Q000145:classification / Q000302:isolation & purification / Q000378:metabolism*; D018988:Bacterial Translocation; D002087:Butyrates / Q000378:metabolism*; D016000:Cluster Analysis; D003430:Cross-Sectional Studies; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004275:DNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D064806:Dysbiosis; D005243:Feces / Q000382:microbiology; D000069196:Gastrointestinal Microbiome; D015658:HIV Infections / Q000150:complications* / Q000473:pathology*; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation; D064307:Microbiota; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D002087:Butyrates; D004269:DNA, Bacterial; D004275:DNA, Ribosomal; D012336:RNA, Ribosomal, 16S