Protective action of Bacillus clausii probiotic strains in an in vitro model of Rotavirus infection

Abstract

Rotavirus is the most common cause of acute gastroenteritis (AGE) in young children. Bacillus clausii (B. clausii) is a spore-forming probiotic that is able to colonize the gut. A mixture of four B. clausii strains (O/C, T, SIN and N/R) is commonly used for the treatment of AGE, and it has been demonstrated that it can reduce the duration and severity of diarrhea in children with AGE. Few studies have sought to characterize the mechanisms responsible for such beneficial effects. Intestinal effects of probiotics are likely to be strain-specific. We conducted a series of in vitro experiments investigating the activities of this mixture of B. clausii strains on biomarkers of mucosal barrier integrity and immune function in a cellular model of Rotavirus infection. B. clausii protected enterocytes against Rotavirus-induced decrease in trans-epithelial electrical resistance, and up-regulated expression of mucin 5AC and tight junction proteins (occludin and zonula occludens-1), all of which are important for effective mucosal barrier function. B. clausii also inhibited reactive oxygen species production and release of pro-inflammatory cytokines (interleukin-8 and interferon-β) in Rotavirus-infected cells, and down-regulated pro-inflammatory Toll-like receptor 3 pathway gene expression. Such mechanisms likely contributed to the observed protective effects of B. clausii against reduced cell proliferation and increased apoptosis in Rotavirus-infected enterocytes. Acute gastroenteritis (AGE), defined as sudden-onset diarrhea that is unrelated to chronic disease, with or without nausea, vomiting, fever or abdominal pain, is disproportionately common among young children 1,2. Rotavirus (RV) is the most common cause of AGE and the leading cause of AGE-associated mortality in children younger than 5 years of age 2-6. In 2016, more than 258 million episodes of diarrhea and approximately 1.5 million hospitalizations and 128,500 deaths in children younger than 5 years were attributable to RV infection globally 2,7. The highest rates of RV-associated mortality have been reported in sub-Saharan Africa, Southeast Asia, and South Asia 7. The high cost of RV vaccination precludes its widespread use in such low-income settings 8. However, even in developed countries, AGE remains a considerable burden, despite the implementation of RV vaccination programs 7. For example, routine RV vaccination was introduced in 2006 in the US, but there were 70,553 AGE-associated hospital admissions, about 20,000 due to RV infection, among US children younger than 5 years in 2013, which were associated with direct costs of more than US $226 million 9. Probiotics are living microorganisms that, when administered in adequate amounts, confer a health benefit on the host after colonizing the gut, and can help to prevent and treat AGE by supporting a healthy gut and immune system 10,11. Short-and long-term beneficial effects of probiotics on the gut are the result of a range of mechanisms, including competitive exclusion and direct antagonism of gut pathogens...

Gut Microbiota and Diarrhea: An Updated Review

“…Thirdly, probiotics can stimulate the production and secretion of mucin, cathelicidins, and defensins from goblet cells and epithelial cells to form an immune barrier, preventing the invasion of pathogenic bacteria ( Do Carmo et al., 2018 ). Meanwhile, probiotics have been reported to increase the expressions of tight junction proteins and reduce the damage to the gut tissues caused by pathogenic bacteria such as E. coli and Rotavirus ( Zeng et al., 2017 ; Paparo et al., 2020 ). More interestingly, Hu Jun et al transplanted fecal microbiota between CM piglets (a native Chinese breed, are more resistant to early-weaning stress-induced diarrhea) and commercial crossbred LY piglets and identified Lactobacillus gasseri LA39 ( L. gasseri LA39) and Lactobacillus frumenti ( L. frumenti ) that could mediate diarrhea resistance.…”

Therapeutic potential of microbial modulation in pancreatic cancer

“… 43 In vitro studies have shown that B. clausii can protect enterocytes from rotavirus infection by improving epithelial barrier function and reducing the production of reactive oxygen species and cytokines like interleukin-8 and interferon-β. 44 B. clausii can also decreased the toxicity of pathogens like Clostridium difficile and Bacillis cereus through secretion of a serine protease. 45 No clinical or preclinical studies have assessed a potential role for B. clausii in the context of cancer.…”

The Effects of a Probiotic (Bacillus clausii) in Acute Kidney Injury in a Rat Model of LPS-Induced Endotoxemia

“…A number of Bacillus strains as probiotic have been studied for their potential functions in vivo and in vitro models (38,39). B. clausii is an endospore-forming, gram-positive, facultative alkaliphilic rod bacterium (15), and is able to grow under aerobic and anaerobic conditions and survive gastric acidity (16,17).…”

“…B. clausii may reveal immunomodulating activity in nasal lavage of allergic children (10). B. clausii inhibited secretion of pro-inflammatory cytokines and reactive oxygen species production in rotavirus-infected cells (39). It was demonstrated that pretreatment with probiotic capsules of Bacillus species spores caused a significant decrement in pro-inflammatory cytokines (42).…”