Colonization of germ-free mice with a mixture of three lactobacillus strains enhances the integrity of gut mucosa and ameliorates allergic sensitization

Abstract

Increasing numbers of clinical trials and animal experiments have shown that probiotic bacteria are promising tools for allergy prevention. Here, we analyzed the immunomodulatory properties of three selected lactobacillus strains and the impact of their mixture on allergic sensitization to Bet v 1 using a gnotobiotic mouse model. We showed that Lactobacillus (L.) rhamnosus LOCK0900, L. rhamnosus LOCK0908 and L. casei LOCK0919 are recognized via Toll-like receptor 2 (TLR2) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) receptors and stimulate bone marrow-derived dendritic cells to produce cytokines in species-and strain-dependent manners. Colonization of germ-free (GF) mice with a mixture of all three strains (Lmix) improved the intestinal barrier by strengthening the apical junctional complexes of enterocytes and restoring the structures of microfilaments extending into the terminal web. Mice colonized with Lmix and sensitized to the Bet v 1 allergen showed significantly lower levels of allergen-specific IgE, IgG1 and IgG2a and an elevated total IgA level in the sera and intestinal lavages as well as an increased transforming growth factor (TGF)-b level compared with the sensitized GF mice. Splenocytes and mesenteric lymph node cells from the Lmix-colonized mice showed the significant upregulation of TGF-b after in vitro stimulation with Bet v 1. Our results show that Lmix colonization improved the gut epithelial barrier and reduced allergic sensitization to Bet v 1. Furthermore, these findings were accompanied by the increased production of circulating and secretory IgA and the regulatory cytokine TGF-b. Thus, this mixture of three lactobacillus strains shows potential for use in the prevention of increased gut permeability and the onset of allergies in humans. Cellular & Molecular Immunology

Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects

“…In addition, L. rhamnosus treatment modulates the immune system (Forsythe et al, 2012;Karimi et al, 2009;Kozakova et al, 2016;Ma et al, 2004), intestinal motility , gut barrier function (Patel et al, 2012;Wang et al, 2012) and enteric nervous system (Kamiya et al, 2006;Ma et al, 2009). Taken together, these preclinical studies identify L. rhamnosus as a candidate psychobiotic with the one of the most comprehensive behavioural, physiological and neurobiological profiles.…”

The influence of gut-derived CD39 regulatory T cells in CNS demyelinating disease

“…The absence of microbes in germ-free mice also affects morphology 32 , angiogenesis 33 and intestinal barrier integrity 61 . A recent study has shown that the colonization with a probiotic mixture of three different Lactobacilli, including Lactobacillus rhamnosus LOCK0900, L. rhamnosus LOCK0908, and L. casei LOCK0919, reduced permeability and improved intestinal morphology.…”

“…A recent study has shown that the colonization with a probiotic mixture of three different Lactobacilli, including Lactobacillus rhamnosus LOCK0900, L. rhamnosus LOCK0908, and L. casei LOCK0919, reduced permeability and improved intestinal morphology. 32 Effects of dysbiosis on the intestinal integrity could affect significantly the levels of gut microbial components, such as endotoxin 29 , and exacerbate disease. However, other mechanisms yet to be described could be responsible for the gut-brain association during CNS inflammation.…”

“…57 SCFAs are more than energy sources and provide immunological benefits to the host by regulating gene expression in immune cells shifting them towards a regulatory phenotype, decreasing oxidative stress, and reinforcing intestinal barrier as well as the blood-brain barrier (BBB), as it will be discussed later. Gut microbes are also essential for the maintenance of intestinal morphology 32 , angiogenesis 33 and intestinal barrier integrity 61 .…”

Diet Matters: Endotoxin in the Diet Impacts the Level of Allergic Sensitization in Germ-Free Mice

“…Data from our lab have shown that this exacerbated allergic sensitization in GF mice can be prevented by mother-to-offspring colonization of GF mice with single probiotic strain B . longum [17] or by colonization of adult GF mice with a mixture of three Lactobacillus strains [26]. Although the gastrointestinal tract of GF animals can be considered sterile, it is still permanently exposed to self-antigens, ingested food antigens [27] and microbial residues in sterile food or beddings, such as endotoxin.…”