Oral Administration of the Probiotic Bifidobacterium Infantis 35624 to Humans Induces Immunoregulatory Responses In Vivo

Purpose: The commensal microbiota is required for optimal host development and ongoing immunological homeostasis, which involves an inter-dependence between microbes and immunity. Microbial dysbiosis has been proposed as one possible explanation for the increased incidence of a wide range of inflammatory disorders, suggesting that manipulation of the microbiota with appropriate microbes may promote immune regulatory mechanisms and reduce aberrant inflammatory activity. Bifidobacterium longum subsp. infantis 35624 (B. infantis) is a commensal microbe which has been extensively studied in murine models and shown to reduce intestinal and extra-intestinal inflammatory responses, in part via the induction of Foxp3+ T regulatory cells. The aim of this study was to determine if B. infantis could influence systemic proinflammatory biomarkers in patients with inflammatory disease. Methods: Healthy human volunteers (n=22), and patients with psoriasis (n=27), ulcerative colitis (n=24) and chronic fatigue syndrome (n=50) were recruited into double-blind, placebo controlled studies whereby individuals received approximately 109 - 1010 B. infantis live cells per day or placebo product for 8 weeks. Plasma was obtained at week 0 and week 8. Cytokine and c-reactive protein (CRP) levels were determined using ultra-sensitive detection kits on the mesoscale discovery multiplex platform. Results: Plasma levels of the anti-inflammatory cytokine, IL-10, were significantly increased in healthy volunteers and psoriasis patients fed B. infantis, but not placebo, for 8 weeks. In contrast, plasma levels of the pro-inflammatory cytokines TNF-alpha and IL-6 were significantly reduced in all patient groups that were administered B. infantis. In addition, associated with decreased pro-inflammatory cytokine levels, plasma CRP levels were also significantly reduced in psoriasis, ulcerative colitis and chronic fatigue syndrome patients at the end of treatment with B. infantis compared to placebo treated patients. Conclusion: The human immunological response to B. infantis further supports the hypothesis that manipulation of the microbiota with specific therapeutic microbes can have a significant effect on host inflammatory processes. The anti-inflammatory effect is not restricted to a specific disease state, suggesting that B. infantis induces a critical cellular response, which may include the induction of regulatory cell subsets. Disclosure: Mr. David Groeger - Employee Alimentary Health Ltd. Dr. Barry Kiely - Employee Alimentary Health Dr. Liam O'Mahony - Consultant Alimentary Health Ltd. Prof. Fergus Shanahan - Consultant Alimentary Health Ltd. Prof. Eamonn M. Quigley - Consultant Alimentary Health Ltd. Prof. Timothy G. Dinan - Consultant Alimentary Health LTd. This research was supported by an industry grant from Alimentary Health Ltd.