Selenomethionine alleviates LPS-induced intestinal injury in rats via coordinated modulation of the microbial-immune...

Selenomethionine (SeMet) is an organic selenium form with high bioavailability. Its regulation of intestinal barrier dysfunction and immune-inflammatory dysregulation through the microbial-immune axis remains incompletely understood. Forty-eight 7-day-old male Sprague-Dawley rats were randomized into four groups: Control, LPS, SeMet, and SeMet‑LPS four groups. Pups received daily oral SeMet (0.2 mg/kg) from postnatal day 7-21, and LPS (10 mg/kg) was intraperitoneally injected after weaning. SeMet pretreatment significantly alleviated LPS-induced growth suppression. It reduced serum and intestinal levels of IL‑6 and TNF‑α and restored antioxidant enzyme activities. Moreover, SeMet upregulated the expression of tight junction proteins ZO‑1 and Claudin‑1. 16S rRNA sequencing revealed that SeMet enriched the beneficial genera Akkermansia and Parasutterella while decreasing pathogenic taxa. Transcriptomic analysis showed that SeMet suppressed activation of the NF‑κB, TNF, and IL‑17 pathways. Microbial-gene association analysis further linked key bacterial genera with host immune and barrier genes, including Traf1, S100a8, Arf4, and Arf6. Collectively, SeMet attenuates LPS-induced intestinal injury by modulating inflammation, oxidative stress, and the microbial-immune axis.