Protective effects of Lactobacillus rhamnosus GG against human rotavirus-induced diarrhoea in a neonatal mouse model

• Published in: Pathogens and disease Vol. 67; no. 3; pp. 184 - 191
• Main Authors: Zhang, Zhen, Xiang, Yun, Li, Na, Wang, Baoxiang, Ai, Hongwu, Wang, Xiaomei, Huang, Laiqiang, Zheng, Yi
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2013; Oxford University Press
• Subjects: Animals; Animals, Newborn; Antibiosis; Biological Therapy - methods; Children; Cytokines - blood; Dehydration; Diarrhea; Diarrhea - pathology; Diarrhea - prevention & control; Diarrhea - therapy; diarrhoea; Disease Models, Animal; Dosage; dosage‐dependent; Epithelium; Female; Gastroenteritis; Gastroenteritis - pathology; Gastroenteritis - prevention & control; Gastroenteritis - therapy; human rotavirus; Humans; Immunoglobulin A; Immunoglobulin A, Secretory - analysis; Infants; Infections; Interferon; Intestinal Mucosa - pathology; Intestine; Jejunum; Lactobacillus rhamnosus; Lactobacillus rhamnosus - physiology; Lactobacillus rhamnosus GG; Mice; Microvillus; Mucosa; Neonates; Rodents; Rotavirus; Rotavirus Infections - pathology; Rotavirus Infections - prevention & control; Rotavirus Infections - therapy; Secretion; timing‐dependent; Treatment Outcome; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors; GG; human rotavirus; timing-dependent; diarrhoea; dosage-dependent
• ISSN: 2049-632X; 2049-632X
• DOI: 10.1111/2049-632X.12030

Abstract Group A human rotaviruses (RV) are a leading cause of severe dehydration and gastroenteritis in infants and young children. A large body of evidence suggests that Lactobacillus rhamnosus GG (LGG) has an effect on the incidence and severity of acute RV-induced diarrhoea; however, the timing and dosage of LGG treatment remains controversial. In the present study, a neonatal mouse model with human RV-induced diarrhoea was set up and the pathophysiological characteristics of the animals were examined. Our results indicated that RV-infected mice developed diarrhoea, accompanied by increased secretion of intestinal mucosa sIgA and serum interferon (IFN)-γ, tumour necrosis factor (TNF)-α, as well as decreased serum IgA. In addition, epithelium vacuolation was noticed in the jejunum microvillus of RV-infected mice. After intragastric administration of low (2 × 10 5 CFU), middle (2 × 10 7 CFU) or high (2 × 10 9 CFU) levels of LGG for four consecutive days before or after RV infection respectively, the RV-infected mice showed a shortened duration of diarrhoea and decreased epithelium vacuolation in the jejunum. Administration of a high dose of LGG before the RV infection was found to have better protective effects against RV infection than other regimens. This study demonstrates that the protective effects of LGG against RV-induced diarrhoea are highly correlated with the timing and dosage of LGG administration in neonatal mice. The manuscript deals with an important topic in mucosal immunology - the mechanism of activity by which probiotics protect against rotavirus (RV)-induced diarrhea. The data shows that in an animal model, administration of Lactobacillus rhamnosus GG (LGG) is associated with higher levels of soluble IgA, and modulation of production of cytokines IFN-[gamma] and TNF-α is observed. These findings may contribute to improve prevention and treatment of RV-induced diarrhea in humans.