Translocation and dissemination of commensal bacteria in post-stroke infection

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.

Prolonged Activation of Invariant Natural Killer T Cells and TH2-Skewed Immunity in Stroke Patients

“…The baseline characteristics and clinical outcomes of the 36 enrolled patients and their age-matched 9 Hospital and 10 Healthy controls were reported previously (13) and detailed here in Table 1. We examined the presence and identity of pathogens in specimens such as blood, urine, and sputum in a prospective manner with strict inclusion/exclusion patient enrollment criteria.…”

“…No culturable organisms were found in the blood, urine, or sputum at any time point of Healthy and Hospital control patients using the same technique. The identity of pathogens found in the specimens of the infected stroke patients was examined and reported (13). The relatively small patient sample size due to strict inclusion/exclusion patient enrollment criteria in this study indeed does not represent the population norm, but the infection incidence is within the range of those reported (14).…”

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

“…Preclinical data from experimental models of ischemic stroke report direct evidence of intestinal barrier dysfunction, which leads to 'bacterial translocation' [130][131][132] . Bacterial translocation can be defined as the invasion of indigenous bacteria or endotoxins across the gut mucosa and into the circulation causing systemic inflammation and distant organ injury 133 .…”

“…In a preclinical model of acute ischemic stroke, Stanley and colleagues observed that intestinal barrier dysfunction correlated with significant enteric neuronal loss in the submucosal plexus of the ileum, which they report may be mediated a misbalance between adrenergic and cholinergic signaling in post-stroke mice. Notably, the structural integrity of the gut barrier was observed at 8 different time points across a 24-hour time period post experimental injury, with intestinal permeability peaking at three hours post-injury 130 . There is also clinical data in support of these experimental findings suggesting stroke induced intestinal barrier dysfunction.…”

“…Despite the debilitating neurological deficits and injury to neuronal tissue, infection, namely bacterial pneumonia, is considered the leading cause of death after stroke 142 . Recent evidence suggests the bacteria responsible for these potentially lethal infections following stroke emanate from the gut 130 . Perhaps this is, in part, caused by intestinal barrier dysfunction whereby indigenous microbial species aberrantly penetrate the compromised barrier?…”