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.
Highlights
In the past decades the commensal gut microbiota has been established as an indispensable major key factor in host physiology
Given a better acceptance by the patients and more practical mode of peroral application of a probiotic formulation as compared to fecal microbiota transplantation (FMT) in both ambulant and hospital settings, we compared the immunopathological impact of the probiotic compound VSL#3 and complex microbiota in the with broadspectrum antibiotics treated host
In order to exclude that upon cessation of antibiotic treatment and peroral reconstitution with VSL#3 remnant commensal bacteria might grow back, we surveyed the intestinal microbiota composition applying highly sensitive and culture-independent 16S rRNA based molecular quantitative RT-PCR
Summary
In the past decades the commensal gut microbiota has been established as an indispensable major key factor in host physiology. Perturbations of the complex host resident intestinal ecologic system, termed dysbiosis, have been linked to a wide range of pathological conditions including intestinal disorders such as inflammatory bowel diseases (IBD; Baumgart and Carding, 2007), irritable bowel syndrome (IBS; Carroll et al, 2010), and coeliac disease (De Palma et al, 2010), as well as extra-intestinal pathologies such as allergy and asthma (Noverr and Huffnagle, 2004), arthritis (Taurog et al, 1994), type 1 diabetes mellitus (Wen et al, 2008), obesity (Backhed et al, 2007), multiple sclerosis (Ochoa-Reparaz et al, 2009), and distinct cardiovascular diseases (Serino et al, 2014) With this growing body of evidence concerning the pivotal role of the microbiota in health and disease, the potential of altering and modulating the microbiota composition in beneficial ways has become an increasing focus of attention. The induction of TGF-β following oral VSL#3 administration was shown to be effective in ameliorating inflammation in a murine model of T-helper (Th-)
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