PLGA-PIP also mitigated pathological damage in major organs, increased duodenal villus height and VH/CD ratio (<i>p</i> < 0.05), upregulated the expression of tight junction proteins (ZO-1, E-cadherin) and endogenous antimicrobial factors (Cryptdin-1, Reg3γ) (<i>p</i> < 0.01), and suppressed the expression of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α (<i>p</i> < 0.01).<h4>Discussion</h4>These findings demonstrate that PLGA-PIP effectively ameliorates ETEC O8-induced sepsis in mice by enhancing intestinal barrier function, reducing pathogen burden, and inhibiting inflammation. Here, TNF is linked to Sepsis.