Burn resuscitation strategy influences the gut microbiota-liver axis in swine

Abstract

AbstractFluid resuscitation improves clinical outcomes of burn patients; however, its execution in resource-poor environments may have to be amended with limited-volume strategies. Liver dysfunction is common in burn patients and gut dysbiosis is an understudied aspect of burn sequelae. Here, the swine gut microbiota and liver transcripts were investigated to determine the impact of standard-of-care modified Brooke (MB), limited-volume colloid (LV-Co), and limited-volume crystalloid (LV-Cr) resuscitation on the gut microbiota, and to evaluate its' potential relationship with liver dysfunction. Independent of resuscitation strategy, bacterial diversity was reduced 24 h post-injury, and remained perturbed at 48 h. Changes in community structure were most pronounced with LV-Co, and correlated with biomarkers of hepatocellular damage. Hierarchical clustering revealed a group of samples that was suggestive of dysbiosis, and LV-Co increased the risk of association with this group. Compared with MB, LV-Co and LV-Cr significantly altered cellular stress and ATP pathways, and gene expression of these perturbed pathways was correlated with major dysbiosis-associated bacteria. Taken together, LV-Co resuscitation exacerbated the loss of bacterial diversity and increased the risk of dysbiosis. Moreover, we present evidence of a linkage between liver (dys)function and the gut microbiota in the acute setting of burn injury.