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 Salmonella enterica serovar Infantis (S. Infantis) infection poses significant risk for the development of non-typhoidal Salmonella gastroenteritis. However, efficient strategies to prevent or treat the infection remain elusive. Here, we explored the effect of the probiotic Lactobacillus rhamnosus GG (LGG) administration in preventing S. Infantis infection in a pig model. Probiotic LGG (1.0 × 1010 CFU/day) was orally administered to newly weaned piglets for 1 week before S. Infantis challenge. LGG pretreatment reduced the severity of diarrhea and alleviated intestinal inflammation caused by S. Infantis. Pre-administration of LGG excluded Salmonella from colonization of the jejunal mucosa but increased the abundance of Bifidobacterium in the feces. LGG promoted the expansion of CD4+ T-bet+ IFNγ+ T cells but attenuated S. Infantis-induced increases in the percentage of CD4+ IFNγ+ T cells and serum interleukin (IL)-22 levels in peripheral blood after S. Infantis challenge. In the small intestine, LGG pretreatment upregulated expression of the transcription factor T-bet but downregulated the S. 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 S. Infantis infection. Pretreatment of pigs with LGG also elevated intestinal IL-22-binding protein production in response to S. Infantis challenge. In contrast, LGG consumption reduced the S. 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 S. Infantis involves the upregulation of T-bet, activation of STAT3, and downregulation of CCL20.

Lactobacillus johnsonii L531 ameliorates enteritis via elimination of damaged mitochondria and suppression of SQSTM1‐dependent mitophagy in a Salmonella infantis model of piglet diarrhea

“…30 S. typhimurium exploits NLRP12-dependent innate immune signaling to suppress host defenses during infection that S. typhimurium induced NLRP12-mediated inhibition of NF-κB by targeting phosphorylation of IκBα in mice. 31 S. enterica serovar 4, [5],12:i:-promotes the phosphorylation of IκBα, activates the NF-κB pathway and upregulates NLRP6 expression. 13 In this study, pIκBα and NF-κB p65 expression both in the ileum and IPEC-J2 cells were upregulated after S. infantis challenge; besides, more NF-κB p65 translocated into nucleus and more neutrophil and lymphocyte infiltration in the jejunum and ileum after S. infantis infection.…”

“…Proximal, mid‐, and distal segments of jejunal and ileal tissues were rinsed with sterile physiologic saline and then fixed in 4% paraformaldehyde. Blinded samples were scored for signs of inflammation, including epithelial cell necrosis, central lacteal expansion, neutrophil and mononuclear cell infiltration, submucosal edema, mucosal hyperemia, and lymphoid necrosis of Peyer’s patches (ileum) based on previously described criteria …”

“…infantis infection model of piglet diarrhea showed that pretreatment with probiotic Lactobacillus rhamnosus GG (LGG) reduces S . infantis colonization in the intestine and ameliorates inflammation and affects the community structure of the gut microbiota . LGG also alleviates inflammation in piglets infected with monophasic variant Salmonella .…”

“…[1][2][3] In newly weaned piglets, S. infantis infection diminishes gut microbiota diversity, potentially leading to enteritis, diarrhea, fever, and poor growth performance. 4,5 Current treatments for Salmonella-related disease rely primarily on antibiotics, thus facilitating the spread of multidrug-resistant bacteria, a serious, worldwide public health problem. Significantly, antibiotic treatment increases the risk of Salmonella infection.…”

An EGFP-marked recombinant lactobacillus oral tetravalent vaccine constitutively expressing α, ε, β1, and β2 toxoids for Clostridium perfringens elicits effective anti-toxins protective immunity

“…Lactobacillus is a Gram-positive, facultative anaerobic or microaerophilic, rod-shaped, non-spore-forming bacteria, which is the most common probiotic found in food and the intestinal tract of humans and animals [16]. Studies have shown that some specific isolates of lactobacilli have potential immunomodulatory properties, such as promoting strong adhesive interactions with intestinal epithelial cells [17] and preventing injury of the epithelial cell barrier [18], anti-inflammatory capacity [19], modulating innate immune response [20] and sIgA production [21], regulating immunological functions of dendritic cells, and T helper cells activation [22,23]. Moreover, lactobacilli can survive transit through the upper gastrointestinal tract and colonize the intestinal tract [24,25].…”