Omega-3 PUFAs Mitigate Polytrauma-Induced Gut-Liver-Lung Inflammation and Organ Dysfunction via GPR120/PPAR-γ

Severe polytrauma frequently triggers a systemic inflammatory response, culminating in fatal Multiple Organ Dysfunction Syndrome (MODS). Although Omega-3 polyunsaturated fatty acids (PUFAs) possess well-documented anti-inflammatory properties, their role in modulating the gut-liver-lung inflammatory axis following polytrauma remains to be fully elucidated. This study investigated whether targeted Omega-3 PUFA administration could mitigate post-traumatic MODS, alongside concurrent changes in intestinal homeostasis and the GPR120/PPAR-γ signaling axis linked to TLR4/NLRP3-associated hyper-inflammation.

Male Sprague-Dawley rats were randomly assigned (computer-generated randomization, n = 6 per group) to Sham, Polytrauma (blunt abdominal trauma + tibial-fibular fracture), and Omega-3 group (300 mg/kg/day via oral gavage). The therapeutic intervention commenced 24 h post-injury and continued daily for 7 consecutive days, with endpoint measurements performed at Day 7. Histological assessments were conducted by investigators blinded to group allocation. We assessed organ injury markers, histological integrity, pro-inflammatory cytokine profiles, colonic GPR120-associated signaling pathways, and the fecal microbiome via 16S rRNA sequencing (n = 6 fecal samples per group).

Omega-3 PUFA administration attenuated polytrauma-induced organ dysfunction (n = 6 per group). Specifically, treatment reduced serum ALT by 51.4% (51.3 ± 8.2 vs 105.6 ± 12.4 U/L in Model group, P = 0.008), AST by 42.4% (141.2 ± 18.5 vs 245.1 ± 22.3 U/L in Model group, P = 0.009), and CK by 48.2% (854.5 ± 112.4 vs 1650.3 ± 156.8 U/L in Model group, P < 0.001). Histological analysis confirmed alleviation of lung injury (score: 2.1 ± 0.2 vs 3.5 ± 0.3; P = 0.012), liver injury (1.7 ± 0.3 vs 3.2 ± 0.2; P = 0.005), and intestinal damage (Chiu's score: 1.6 ± 0.3 vs 3.2 ± 0.2; P = 0.008), alongside preserved goblet cell counts and ZO-1 expression. 16S rRNA sequencing (n = 6 per group) further revealed recovery in microbial alpha-diversity. Compared with the Model group, the Omega-3 group exhibited increased Shannon index (4.02 ± 0.18 vs 3.41 ± 0.32, P = 0.008) and Chao1 index (442.6 ± 41.5 vs 368.2 ± 39.1, P = 0.006). Taxonomic differences across groups were determined using Linear Discriminant Analysis Effect Size (LEfSe). Western blot and qRT-PCR analyses indicated that these protective phenotypic changes were associated with reduced expression of TLR4, NLRP3, and p-p65/total p65 ratio, as well as upregulation of GPR120 and PPAR-γ.

Targeted Omega-3 PUFA administration may mitigate polytrauma-induced systemic inflammation and multi-organ dysfunction. These protective effects appear to be associated with maintained intestinal barrier integrity, altered gut microbiota composition, and shifts in GPR120/PPAR-γ pathway activity. These findings suggest that Omega-3 PUFAs warrant further preclinical and translational evaluation as a potential immunonutritional strategy for traumatic MODS management.