Lactobacillus plantarum alleviates irradiation‐induced intestinal injury by activation of FXR‐FGF15 signaling in intestinal epithelia

Abstract Background: Clostridium perfringens causes intestinal injury through overgrowth and secretion of multiple toxins, leading to diarrhea and necrotic enteritis in animals, such as pigs. Lactobacillus plantarum (L. plantarum) Lac16 has been reported to protect broilers against C. perfringens infection. This study aimed at investigating the protective effects of Lactobacillus plantarum Lac16 on C. perfringens infection-associated intestinal injury in intestinal porcine epithelial cell line (IPEC-J2). Results: The results showed that L. plantarum Lac16 significantly inhibit the growth and biofilm formation of C. perfringens (P < 0.001). In the co-culture system, L. plantarum Lac16 significantly suppressed colony forming units (CFU) of C. perfringens (P < 0.05), which was accompanied by a decrease in pH levels (P < 0.01). Moreover, L. plantarum Lac16 significantly elevated the mRNA expression levels of host defense peptides (HDPs) in IPEC-J2 cells (P < 0.05), decreased C. perfringens-induced cellular cytotoxicity (P < 0.01) and adhesion to cells (P < 0.05). At the same time, L. plantarum Lac16 significantly attenuated C. perfringens-induced damage to intestinal barrier integrity and the decrease in claudin-1 (P < 0.01) as well as zona occludens 1 (ZO-1) expressions. Preincubation with L. plantarum Lac16 significantly suppressed mRNA expression levels of pattern recognition receptors (PRRs) (Toll-like receptor (TLR) 1, TLR2, nucleotide-binding oligomerization domain (NOD) 1) in C. perfringens-challenged IPEC-J2 cells (P < 0.01). C. perfringens significantly elevated the phosphorylation of p38 mitogen-activated protein kinase (MAPK), JNK, and p65 nuclear factor-κB (NF-κB) (P < 0.05) while L. plantarum Lac16 pre-incubation effectively inhibited phosphorylation of p65 (P < 0.001). Furthermore, L. plantarum Lac16 significantly suppressed C. perfringens induced gene expressions of proinflammatory cytokines (interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α (TNF-α)) (P < 0.05). Conclusions: Collectively, probiotic L. plantarum Lac16 exerts protective effects against C. perfringens infection-associated intestinal injury in IPEC-J2 cells.

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Oral PEG 15–20 protects the intestine against radiation: role of lipid rafts

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00328.2009 ◽

2009 ◽

Vol 297 (6) ◽

pp. G1041-G1052 ◽

Cited By ~ 18

Author(s):

Vesta Valuckaite ◽

Olga Zaborina ◽

Jason Long ◽

Martin Hauer-Jensen ◽

Junru Wang ◽

...

Keyword(s):

Epithelial Cells ◽

Lipid Rafts ◽

Intestinal Epithelial Cells ◽

Clinical Problem ◽

Intestinal Wall ◽

Intestinal Injury ◽

Dependent Manner ◽

Intestinal Epithelial ◽

Intestinal Epithelia ◽

Lethal Sepsis

Intestinal injury following abdominal radiation therapy or accidental exposure remains a significant clinical problem that can result in varying degrees of mucosal destruction such as ulceration, vascular sclerosis, intestinal wall fibrosis, loss of barrier function, and even lethal gut-derived sepsis. We determined the ability of a high-molecular-weight polyethylene glycol-based copolymer, PEG 15–20, to protect the intestine against the early and late effects of radiation in mice and rats and to determine its mechanism of action by examining cultured rat intestinal epithelia. Rats were exposed to fractionated radiation in an established model of intestinal injury, whereby an intestinal segment is surgically placed into the scrotum and radiated daily. Radiation injury score was decreased in a dose-dependent manner in rats gavaged with 0.5 or 2.0 g/kg per day of PEG 15–20 ( n = 9–13/group, P < 0.005). Complementary studies were performed in a novel mouse model of abdominal radiation followed by intestinal inoculation with Pseudomonas aeruginosa ( P. aeruginosa ), a common pathogen that causes lethal gut-derived sepsis following radiation. Mice mortality was decreased by 40% in mice drinking 1% PEG 15–20 ( n = 10/group, P < 0.001). Parallel studies were performed in cultured rat intestinal epithelial cells treated with PEG 15–20 before radiation. Results demonstrated that PEG 15–20 prevented radiation-induced intestinal injury in rats, prevented apoptosis and lethal sepsis attributable to P. aeruginosa in mice, and protected cultured intestinal epithelial cells from apoptosis and microbial adherence and possible invasion. PEG 15–20 appeared to exert its protective effect via its binding to lipid rafts by preventing their coalescence, a hallmark feature in intestinal epithelial cells exposed to radiation.

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