Decoding the gut interactome after severe trauma: from molecular dialogue to integrative treatment strategies

Severe trauma constitutes not merely a localized injury, but a systemic insult to the host's barrier systems driven by massive hemorrhage, hemorrhagic shock, and the systemic inflammatory response. Rather than being a passive victim of this cascade, the gut is widely considered a critical mediator contributing to the pathogenesis of remote MODS. The concept of the interactome redefines disease outcome as the product of a dynamic and reciprocal dialogue among host immune status, gut microbiota structure and function, and pathogen virulence expression. This framework offers a conceptual shift from the traditional single-pathogen model. Based on the interactome theory, this paper systematically reviews the current understanding of the evolution of intestinal microecology from symbiotic homeostasis to pathobiome after severe trauma. These include intestinal epithelial energy metabolism crisis induced by shock and hypoperfusion, excessive activation of pattern recognition receptors in the context of concurrent DAMPs and PAMPs, loss of mucosal protection associated with aryl hydrocarbon receptor ligand depletion, cytotoxic transformation suggested to be linked to bile acid metabolism disorder, and iatrogenic stress destruction of colonization resistance. On this basis, this paper outlines an integrated treatment strategy grounded in molecular targets. The strategy encompasses metabolic substrate supplementation with short-chain fatty acids and prebiotics, AhR signal reactivation via dietary tryptophan and phytochemicals, pathogenic group clearance and virulence inhibition using multi-targeted traditional Chinese medicine compounds, neuroimmune regulation through acupuncture, and a new clinical pathway combining dietary pre-rehabilitation with dynamic functional omics monitoring. Finally, we argue that future therapeutic strategies may benefit from shifting from pathogen eradication toward restoring host-microbiota symbiosis. This review provides a systematic framework for the precision intervention of post-traumatic gut microecology, spanning from molecular mechanisms to clinical translation.