Oral Administration of Lactobacillus rhamnosus GG Ameliorates Salmonella Infantis-Induced Inflammation in a Pig Model via Activation of the IL-22BP/IL-22/STAT3 Pathway

Abstract

The high rate of <i>Salmonella enterica</i> serovar Infantis (<i>S</i>. Infantis) infection poses significant risk for the development of non-typhoidal <i>Salmonella</i> gastroenteritis. However, efficient strategies to prevent or treat the infection remain elusive. Here, we explored the effect of the probiotic <i>Lactobacillus rhamnosus</i> GG (LGG) administration in preventing <i>S</i>. Infantis infection in a pig model. Probiotic LGG (1.0 × 10¹⁰ CFU/day) was orally administered to newly weaned piglets for 1 week before <i>S</i>. Infantis challenge. LGG pretreatment reduced the severity of diarrhea and alleviated intestinal inflammation caused by <i>S</i>. Infantis. Pre-administration of LGG excluded <i>Salmonella</i> from colonization of the jejunal mucosa but increased the abundance of <i>Bifidobacterium</i> in the feces. LGG promoted the expansion of CD4⁺ T-bet⁺ IFNγ⁺ T cells but attenuated <i>S</i>. Infantis-induced increases in the percentage of CD4⁺ IFNγ⁺ T cells and serum interleukin (IL)-22 levels in peripheral blood after <i>S</i>. Infantis challenge. In the small intestine, LGG pretreatment upregulated expression of the transcription factor T-bet but downregulated the <i>S</i>. Infantis-induced increase of CD4⁺ IFNγ⁺ T cells in Peyer's patches and IL-7Rα expression in the jejunum. Notably, LGG-treated pigs had enhanced expression of IL-22 and activated STAT3 in the ileum in response to <i>S</i>. Infantis infection. Pretreatment of pigs with LGG also elevated intestinal IL-22-binding protein production in response to <i>S</i>. Infantis challenge. In contrast, LGG consumption reduced the <i>S</i>. Infantis-induced increase in the number of CCL20-expressing cells in the jejunum. Our results suggest that the mechanism by which LGG ameliorates the intestinal inflammation caused by <i>S</i>. Infantis involves the upregulation of T-bet, activation of STAT3, and downregulation of CCL20.