Colonization of preterm gnotobiotic piglets with probioticLactobacillus rhamnosusGG and its interference withSalmonellaTyphimurium

Abstract

Summary A balanced microbiota of the gastrointestinal tract (GIT) is a prerequisite for a healthy host. The GIT microbiota in preterm infants is determined by the method of delivery and nutrition. Probiotics can improve the GIT microbiota balance and suitable animal models are required to verify their harmlessness. Preterm gnotobiotic piglets were colonized with Lactobacillus rhamnosus GG (LGG) to evaluate its safety and possible protective action against infection with an enteric pathogen, Salmonella Typhimurium (ST). Clinical signs (anorexia, somnolence, fever and diarrhea), bacterial interference and translocation, intestinal histopathology, transcriptions of claudin‐1, occludin and interferon (IFN)‐γ, intestinal and systemic protein levels of interleukin (IL)‐8, IL‐12/23 p40 and IFN‐γ were compared among (i) germ‐free, (ii) LGG‐colonized, (iii) ST‐infected and (iv) LGG‐colonized and subsequently ST‐infected piglets for 24 h. Both LGG and ST‐colonized the GIT; LGG translocated in some cases into mesenteric lymph nodes and the spleen but did not cause bacteremia and clinical changes. ST caused clinical signs of gastroenteritis, translocated into mesenteric lymph nodes, the spleen, liver and blood, increased claudin‐1 and IFN‐γ transcriptions, but decreased occludin transcription and increased local and systemic levels of IL‐8 and IL‐12/23 p40. Previous colonization with LGG reduced ST colonization in the jejunum and translocation into the liver, spleen and blood. It partially ameliorated histopathological changes in the intestine, reduced IL‐8 levels in the jejunum and plasma and IL‐12/23 p40 in the jejunum. The preterm gnotobiotic piglet model of the vulnerable preterm immunocompromised infant is useful to verify the safety of probiotics and evaluate their protective effect.

Histological and Comparative Transcriptome Analyses Provide Insights into Small Intestine Health in Diarrheal Piglets after Infection with Clostridium Perfringens Type C

“…It is known that pigs challenged by various pathogenic bacteria display diarrhea, growth retardation, and high fever [22,34,35]. In our study, we also found that piglets in TG exhibited diarrhea and body weight loss (Figure 1A,C), which suggested that C. perfringens type C and its fatal toxins could impair the integrity of the intestinal barrier and then caused diarrhea; persistent diarrhea then led to body weight loss.…”

Colonization of Germ-Free Piglets with Commensal Lactobacillus amylovorus, Lactobacillus mucosae, and Probiotic E. coli Nissle 1917 and Their Interference with Salmonella Typhimurium

“…Concordantly, IL-8 levels in plasma was found in the experiment with preterm less mature gnotobiotic piglets infected with S . Typhimurium [21]. Lower levels of plasma TNF-α compared with our previous results [58] were found.…”

“…Thirty evenly spaced radial lamina mucosalis propria widths per each piglet were measured. Histological scoring was evaluated as described elsewhere [21]. Briefly: i) Submucosal edema (0–2); ii) PMNs (polymorphonuclear neutrophils) infiltration into the lamina propria (0–2); iii) villus atrophy (0–3); iv) exudate in lumen (0–2); v) vessels dilatation (0–2); vi) inflammatory cellularity in lymphatic vessel lumen (0–2); vii) hyperemia (0–2); viii) hemorrhage (0–2); ix) peritonitis (0–1); or x) erosion of the epithelial layer (0–3).…”

“…Due to its genetics, physiology, and anatomy, the pig is commonly used in biomedical research and it is a suitable model of human gastrointestinal [18] and infectious diseases [19]. Gnotobiotic animals, with their simple and defined microbiota, enable investigations of interactions among different bacterial species and strains and interactions between microbiota and its host [20,21,22].…”

High Mobility Group Box 1 and TLR4 Signaling Pathway in Gnotobiotic Piglets Colonized/Infected with L. amylovorus, L. mucosae, E. coli Nissle 1917 and S. Typhimurium

“…Salmonella Typhimurium strain LT2 is a well-characterized laboratory strain [58]. It was safe for one-week-old conventional piglets after its oral application [59], but it caused gastroenteritis and sepsis in immunocompromised germ-free piglets of the same age [60].…”