Translocation and dissemination of commensal bacteria in post-stroke infection

Nat Med. 2016 Nov;22(11):1277-1284. doi: 10.1038/nm.4194. Epub 2016 Oct 3.

Abstract

Bacterial infection is highly prevalent in patients who have had a stroke. Despite the potential contribution of micro-aspiration in post-stroke pneumonia, we found that the majority of the microorganisms detected in the patients who developed infections after having a stroke were common commensal bacteria that normally reside in the intestinal tracts. In a mouse model of ischemic stroke, post-stroke infection was only observed in mice that were born and raised in specific-pathogen-free facilities; this was not seen in mice that were born and raised in germ-free facilities. Using high-throughput 16S rRNA gene amplicon sequencing and bioinformatics analyses, we provide evidence demonstrating that the source of the bacteria forming the microbial community in the lungs of post-stroke mice was indeed the host small intestine. Additionally, stroke-induced gut barrier permeability and dysfunction preceded the dissemination of orally inoculated bacteria to peripheral tissues. This study identifies a novel pathway in which stroke promotes the translocation and dissemination of selective strains of bacteria that originated from the host gut microbiota.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Aged
  • Aged, 80 and over
  • Animals
  • Bacteremia / immunology
  • Bacteremia / metabolism
  • Bacteremia / microbiology
  • Bacterial Infections / immunology*
  • Bacterial Infections / metabolism
  • Bacterial Infections / microbiology
  • Bacterial Translocation / immunology*
  • Blood Culture
  • Computational Biology
  • Disease Models, Animal
  • Enterococcus faecalis
  • Female
  • Gastrointestinal Microbiome / genetics*
  • Goblet Cells / cytology
  • Goblet Cells / metabolism
  • Gram-Positive Bacterial Infections / immunology*
  • Gram-Positive Bacterial Infections / metabolism
  • Gram-Positive Bacterial Infections / microbiology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Infarction, Middle Cerebral Artery / immunology
  • Intestine, Small / cytology
  • Intestine, Small / drug effects
  • Intestine, Small / metabolism*
  • Intestine, Small / microbiology
  • Male
  • Mice
  • Microbiota / genetics
  • Middle Aged
  • Permeability / drug effects
  • Pneumonia, Bacterial / immunology
  • Pneumonia, Bacterial / metabolism
  • Pneumonia, Bacterial / microbiology
  • RNA, Ribosomal, 16S / genetics*
  • Receptors, Adrenergic, beta / metabolism
  • Sequence Analysis, RNA
  • Specific Pathogen-Free Organisms
  • Stroke / immunology*
  • Urinary Tract Infections / immunology
  • Urinary Tract Infections / metabolism
  • Urinary Tract Infections / microbiology
  • Zonula Occludens-1 Protein / metabolism

Substances

  • Adrenergic beta-Antagonists
  • RNA, Ribosomal, 16S
  • Receptors, Adrenergic, beta
  • Tjp1 protein, mouse
  • Zonula Occludens-1 Protein