Nonselective beta blockade enhances gut microbiome diversity in a rodent model of trauma, hemorrhage, and chronic stress

Abstract

BACKGROUND Traumatic injury leads to gut dysbiosis with changes in microbiome diversity and conversion toward a “pathobiome” signature characterized by a selective overabundance of pathogenic bacteria. The use of non-selective beta antagonism in trauma patients has been established as a useful adjunct to reduce systemic inflammation. We sought to investigate whether beta-adrenergic blockade following trauma would prevent the conversion of microbiome to a “pathobiome” phenotype. METHODS Sprague-Dawley rats (n = 6–8/group) were subjected to routine daily handling (naïve), lung contusion with hemorrhagic shock (LCHS), or LCHS with daily chronic stress (LCHS/CS), each with or without administration of intraperitoneal propranolol (BB) (10 mg/kg/day). Fecal microbiome was measured on Days 0, 7, and 14 using high-throughput 16S rRNA sequencing and QIIME2 bioinformatics analyses. Alpha- and beta-diversity and microbiome composition were assessed with significance defined as *p < 0.05. RESULTS Use of propranolol following LCHS or LCHS/CS demonstrated a significant increase in the number of bacterial species (Chao1 index), as well as overall richness and evenness (Shannon index) compared with their untreated counterparts at Day 7. By Day 14, these differences were no longer apparent between BB and untreated groups subjected to LCHS/CS. There was an abundance of commensal bacteria such as Oscillospiraceae and Clostridia in LCHS and LCHS/CS treated with BB after 7 days which persisted at 14 days. CONCLUSION These findings suggest a role for beta-antagonism in altering the diversity of the gut microbiome and the need for further studies to elucidate the cellular and molecular mechanisms underlying this intriguing connection of microbiome with trauma and beta-blockade.