title: A core microbiome associated with the peritoneal tumors of pseudomyxoma peritonei.
abstract: BACKGROUND
  Pseudomyxoma peritonei (PMP) is a malignancy characterized by dissemination of mucus-secreting cells throughout the peritoneum. This disease is associated with significant morbidity and mortality and despite effective treatment options for early-stage disease, patients with PMP often relapse. Thus, there is a need for additional treatment options to reduce relapse rate and increase long-term survival. A previous study identified the presence of both typed and non-culturable bacteria associated with PMP tissue and determined that increased bacterial density was associated with more severe disease. These findings highlighted the possible role for bacteria in PMP disease.
  
  
  METHODS
  To more clearly define the bacterial communities associated with PMP disease, we employed a sequenced-based analysis to profile the bacterial populations found in PMP tumor and mucin tissue in 11 patients. Sequencing data were confirmed by in situ hybridization at multiple taxonomic depths and by culturing. A pilot clinical study was initiated to determine whether the addition of antibiotic therapy affected PMP patient outcome.
  
  
  RESULTS
  We determined that the types of bacteria present are highly conserved in all PMP patients; the dominant phyla are the Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. A core set of taxon-specific sequences were found in all 11 patients; many of these sequences were classified into taxonomic groups that also contain known human pathogens. In situ hybridization directly confirmed the presence of bacteria in PMP at multiple taxonomic depths and supported our sequence-based analysis. Furthermore, culturing of PMP tissue samples allowed us to isolate 11 different bacterial strains from eight independent patients, and in vitro analysis of subset of these isolates suggests that at least some of these strains may interact with the PMP-associated mucin MUC2. Finally, we provide evidence suggesting that targeting these bacteria with antibiotic treatment may increase the survival of PMP patients.
  
  
  CONCLUSIONS
  Using 16S amplicon-based sequencing, direct in situ hybridization analysis and culturing methods, we have identified numerous bacterial taxa that are consistently present in all PMP patients tested. Combined with data from a pilot clinical study, these data support the hypothesis that adding antimicrobials to the standard PMP treatment could improve PMP patient survival.
authors.affiliation: Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Gilbreath
authors.forename: Cristina
authors.initials: C
authors.lastname: Semino-Mora
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Friedline
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Kip L
authors.initials: KL
authors.lastname: Bodi
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: McAvoy
authors.forename: Jennifer
authors.initials: J
authors.lastname: Francis
authors.forename: Carol
authors.initials: C
authors.lastname: Nieroda
authors.forename: Armando
authors.initials: A
authors.lastname: Sardi
authors.forename: Andre
authors.initials: A
authors.lastname: Dubois
authors.forename: David W
authors.initials: DW
authors.lastname: Lazinski
authors.forename: Andrew
authors.initials: A
authors.lastname: Camilli
authors.forename: Traci L
authors.initials: TL
authors.lastname: Testerman
authors.forename: D Scott
authors.initials: DS
authors.lastname: Merrell
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001419:Bacteria / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification*; D001424:Bacterial Infections / Q000150:complications* / Q000188:drug therapy / Q000382:microbiology; D003470:Culture Media; D006801:Humans; D017403:In Situ Hybridization; D064307:Microbiota; D055262:Mucin-2 / Q000378:metabolism; D009077:Mucins / Q000378:metabolism; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000382:microbiology* / Q000401:mortality; D010537:Peritoneum / Q000378:metabolism / Q000382:microbiology; D011379:Prognosis; D011553:Pseudomyxoma Peritonei / Q000188:drug therapy / Q000382:microbiology* / Q000401:mortality; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D003470:Culture Media; D055262:Mucin-2; D009077:Mucins; D012336:RNA, Ribosomal, 16S