Introduction:While recent reports underscore the significance of the gut microbiome (GM) in health and disease, its importance in burn outcomes remains unclear. Moreover, aggressive intravenous (IV) fluid resuscitation of patients may alter intestinal flora. Herein, we describe GM changes following a large burn in swine randomized to different volumes of IV Lactated Ringers' (LR).Methods:Anesthetized Yorkshire swine sustained 40% total body surface area full-Thickness burns and were randomized to different volumes of IV LR: none (n=5), 15mL/kg/d (low; n=6), or 80mL/kg/d (high; n=6). At baseline and days 1 and 2, fecal swabs were collected for 16s rDNA sequencing. Proximal jejunum was collected immediately after euthanasia (day 2) for western blot, histopathology, and cytokine analyses.Results:Burns produced significant shifts in β-diversity and non-significant reductions in α-diversity that did not recover regardless of treatment group. Burn-induced increases in Proteobacteria and decreases in Firmicutes were attenuated by IV fluids in a dose-dependent manner, and also correlated with α-diversity. IV fluids caused a dose-dependent increase in Bacteroides and prevented a transient increase in the opportunistic pathogen Haemophilus parainfluenzae. While high volumes of IV fluids increased intestinal Hsp70 levels (P=0.0464), they reduced SGLT1 (P=0.0213) and caspase3 (P=0.0139) levels. IV fluids elicited a non-specific cytokine response; however, Bacteroidetes levels correlated with intestinal IL18 levels (P=0.0166, R2=0.4201).Conclusions:We present the first report on the gut microbiome in a porcine burn model, and present data to suggest that IV fluids may influence GM and gut functional proteins following a burn. Overall, burn-induced GM diversity shifts may expose diagnostic and/or therapeutic targets to improve outcomes.