The Probiotic Compound VSL#3 Modulates Mucosal, Peripheral, and Systemic Immunity Following Murine Broad-Spectrum Antibiotic Treatment

Abstract

There is compelling evidence linking the commensal intestinal microbiota with host health and, in turn, antibiotic induced perturbations of microbiota composition with distinct pathologies. Despite the attractiveness of probiotic therapy as a tool to beneficially alter the intestinal microbiota, its immunological effects are still incompletely understood. The aim of the present study was to assess the efficacy of the probiotic formulation VSL#3 consisting of eight distinct bacterial species (including Streptococcus thermophilus, Bifidobacterium breve, B. longum, B. infantis, Lactobacillus acidophilus, L. plantarum, L. paracasei, and L. delbrueckii subsp. Bulgaricus) in reversing immunological effects of microbiota depletion as compared to reassociation with a complex murine microbiota. To address this, conventional mice were subjected to broad-spectrum antibiotic therapy for 8 weeks and perorally reassociated with either VSL#3 bacteria or a complex murine microbiota. VSL#3 recolonization resulted in restored CD4+ and CD8+ cell numbers in the small and large intestinal lamina propria as well as in B220+ cell numbers in the former, whereas probiotic intervention was not sufficient to reverse the antibiotic induced changes of respective cell populations in the spleen. However, VSL#3 application was as efficient as complex microbiota reassociation to attenuate the frequencies of regulatory T cells, activated dendritic cells and memory/effector T cells in the small intestine, colon, mesenteric lymph nodes, and spleen. Whereas broad-spectrum antibiotic treatment resulted in decreased production of cytokines such as IFN-γ, IL-17, IL-22, and IL-10 by CD4+ cells in respective immunological compartments, VSL#3 recolonization was sufficient to completely recover the expression of the anti-inflammatory cytokine IL-10 without affecting pro-inflammatory mediators. In summary, the probiotic compound VSL#3 has an extensive impact on mucosal, peripheral, and systemic innate as well as adaptive immunity, exerting beneficial anti-inflammatory effects in intestinal as well as systemic compartments. Hence, VSL#3 might be considered a therapeutic immunomodulatory tool following antibiotic therapy.

In Vitro Evaluation of the Impact of the Probiotic E. coli Nissle 1917 on Campylobacter jejuni’s Invasion and Intracellular Survival in Human Colonic Cells

“…In light of the increase in antibiotic resistant C. jejuni ( Kassem et al, 2016a ), there is a need to proactively devise alternative approaches to control the proliferation of this pathogen and cognate infections. Several studies have recently investigated the effect of probiotic bacteria on C. jejuni infections in cell lines ( in vitro ) and in animal models such as chickens, a primary host and source of this bacterium ( Baffoni et al, 2017 ; Ekmekciu et al, 2017 ; Johnson et al, 2017 ). Lactobacillus , Bacillus , and Enterococcus have been among the most commonly researched probiotic bacteria against C. jejuni ( Johnson et al, 2017 ).…”

Faecal and mucosal microbiota in patients with functional gastrointestinal disorders: Correlation with toll-like receptor 2/toll-like receptor 4 expression

“…thermophilus , are not pathogenic[ 17 ] and are part of the commensal human microbiota of the mouth, skin, intestine, and upper respiratory tract. S. thermophilus is considered a probiotic and is a key strain of VSL#3, which is considered a therapeutic immunomodulatory tool[ 18 ]. Streptococcaceae was negatively correlated with TLR2 expression in samples of both MAM and LM in our study.…”

Fecal Microbiota Transplantation, Commensal Escherichia coli and Lactobacillus johnsonii Strains Differentially Restore Intestinal and Systemic Adaptive Immune Cell Populations Following Broad-spectrum Antibiotic Treatment

“…In our previous works, we have shown that normally developed mice rendered void of intestinal microbiota through a quintuple antibiotic therapy (i.e., secondary abiotic mice, ABx mice), display numerous changes of intestinal mucosal and systemic immune cell subsets, which can, however, almost completely be restored through reintroduction of intestinal antigens via fecal microbiota transplantation (FMT) ( Ekmekciu et al, 2017a , b ). Furthermore we were able to demonstrate that recolonization of ABx mice with VSL#3, a probiotic mixture consisting of eight bacterial species (namely Streptococcus thermophilus , Bifidobacterium breve , B. longum , B. infantis , Lactobacillus acidophilus , L. plantarum , L. paracasei , and L. delbrueckii subsp.…”