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Randomized Controlled Trial
. Jul-Aug 2013;4(4):325-39.
doi: 10.4161/gmic.25487. Epub 2013 Jun 21.

Bifidobacterium Infantis 35624 Modulates Host Inflammatory Processes Beyond the Gut

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Free PMC article
Randomized Controlled Trial

Bifidobacterium Infantis 35624 Modulates Host Inflammatory Processes Beyond the Gut

David Groeger et al. Gut Microbes. .
Free PMC article

Abstract

Certain therapeutic microbes, including Bifidobacteria infantis (B. infantis) 35624 exert beneficial immunoregulatory effects by mimicking commensal-immune interactions; however, the value of these effects in patients with non-gastrointestinal inflammatory conditions remains unclear. In this study, we assessed the impact of oral administration of B. infantis 35624, for 6‒8 weeks on inflammatory biomarker and plasma cytokine levels in patients with ulcerative colitis (UC) (n = 22), chronic fatigue syndrome (CFS) (n = 48) and psoriasis (n = 26) in three separate randomized, double-blind, placebo-controlled interventions. Additionally, the effect of B. infantis 35624 on immunological biomarkers in healthy subjects (n = 22) was assessed. At baseline, both gastrointestinal (UC) and non-gastrointestinal (CFS and psoriasis) patients had significantly increased plasma levels of C-reactive protein (CRP) and the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) compared with healthy volunteers. B. infantis 35624 feeding resulted in reduced plasma CRP levels in all three inflammatory disorders compared with placebo. Interestingly, plasma TNF-α was reduced in CFS and psoriasis while IL-6 was reduced in UC and CFS. Furthermore, in healthy subjects, LPS-stimulated TNF-α and IL-6 secretion by peripheral blood mononuclear cells (PBMCs) was significantly reduced in the B. infantis 35624-treated groups compared with placebo following eight weeks of feeding. These results demonstrate the ability of this microbe to reduce systemic pro-inflammatory biomarkers in both gastrointestinal and non-gastrointestinal conditions. In conclusion, these data show that the immunomodulatory effects of the microbiota in humans are not limited to the mucosal immune system but extend to the systemic immune system.

Keywords: B. infantis35624; C-reactive protein; immunity; inflammation; microbiota.

Figures

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Figure 1. Plasma pro-inflammatory biomarkers are elevated in patients with inflammatory disorders. Plasma CRP and pro-inflammatory cytokines levels are significantly elevated in chronic fatigue syndrome (CFS) (n = 48), psoriasis (n = 26) and ulcerative colitis (UC) (n = 22) patients compared with healthy volunteers (n = 35). Results are expressed as median values. (Healthy volunteers vs. each inflammatory disorder) (Mann-Whitney U test) p < 0.05 *, p < 0.01 ** p < 0.01 ***.
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Figure 2.B. infantis 35624-feeding reduces plasma CRP levels compared with placebo. Plasma levels of CRP were significantly reduced in the B. infantis 35624 treated groups compared with placebo treatment following 6–8 weeks of feeding in patients with chronic fatigue syndrome (CFS), psoriasis and ulcerative colitis (UC). Results are expressed as the change from baseline (post-treatment minus pre-treatment level) for each patient. *p < 0.05 vs. placebo; (Mann-Whitney U test).
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Figure 3.B. infantis 35624-feeding reduces plasma CRP levels compared with pretreatment level. Placebo-feeding for 8 weeks did not alter plasma CRP levels compared with pretreatment levels in any patients with inflammatory disorders. Plasma CRP levels were significantly reduced following 8 weeks of feeding with B. infantis 35624 compared with pretreatment levels in (A) psoriasis (n = 12). and (B) chronic fatigue syndrome (CFS) (n = 28), However, there was no difference in CRP levels following 6 weeks feeding with B. infantis 35624 in patients with (C) ulcerative colitis (UC) (n = 13) compared with their pretreatment levels. Results are expressed as the individual responses of each patient (mg/L) (pre-treatment vs. post-treatment level) *p < 0.05 (Wilcoxon matched pair test).
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Figure 4.B. infantis 35624-feeding reduces plasma TNF-α levels compared with placebo. Plasma levels of TNF-α were significantly reduced in the B. infantis 35624-treated groups compared with placebo treatment following 8 weeks of feeding in patients with chronic fatigue syndrome (CFS) and psoriasis. However, there was no difference in TNF-α levels following 6 weeks feeding with B. infantis 35624 in patients with ulcerative colitis (UC) compared with placebo treatment. Results are expressed as the change from baseline (post-treatment minus pre-treatment level) for each patient. *p < 0.05 vs. placebo; (Mann-Whitney U test).
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Figure 5.B. infantis 35624-feeding reduces plasma TNF-α levels compared with pretreatment level. Placebo treatment did not alter plasma TNF-α levels, compared with pretreatment levels, in all the patient groups tested. Plasma TNF-α levels were significantly reduced following 8 weeks of feeding with B. infantis 35624, compared with pretreatment levels, in (A) psoriasis (n = 12) and (B) chronic fatigue syndrome (CFS) (n = 28). However there was no difference in TNF-α levels following 6 weeks feeding with B. infantis 35624 in patients with (C) ulcerative colitis (UC) (n = 13) compared with their pretreatment levels. Results are expressed as the individual responses of each patient (pg/ml) (pre-treatment vs. post-treatment level) *p < 0.05 (Wilcoxon matched pair test).
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Figure 6.B. infantis 35624-feeding reduces plasma IL-6 levels compared with placebo. Plasma levels of IL-6 were reduced in the B. infantis 35624 treated groups compared with placebo treatment following 6–8 weeks of feeding in patients with chronic fatigue syndrome (CFS) (#p = 0.054) and ulcerative colitis (UC) (~p = 0.057). However, there was no difference in IL-6 levels following 8 weeks feeding with B. infantis 35624 in patients with psoriasis compared with placebo treatment. Results are expressed as the change from baseline (post-treatment minus pre-treatment level) for each patient. *p < 0.05 vs. placebo groups (Mann-Whitney U test).
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Figure 7.B. infantis 35624-feeding reduces plasma IL-6 levels compared with pretreatment level. There was no change in plasma IL-6 levels following 8 weeks feeding with placebo, compared with pretreatment levels, in patients with inflammatory disorders. Plasma IL-6 levels were significantly reduced following 8 weeks of feeding with B. infantis 35624 compared with pretreatment levels in patients with chronic fatigue syndrome (CFS) (n = 28). However, there was no difference in IL-6 levels following 6 or 8 weeks feeding respectively with B. infantis 35624 in patients with ulcerative colitis (UC) (n = 13) or psoriasis (n = 12) compared with their pretreatment levels. Results are expressed as the individual responses of each patient (pg/ml) (pre-treatment vs. post-treatment level) **p < 0.01 (Wilcoxon matched pair test).
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Figure 8.B. infantis 35624-feeding reduces pro-inflammatory biomarkers in a highly correlated way in inflammatory disorder patients. 3D Cluster analysis of plasma levels of CRP (z), TNF-α (x) and IL-6 (y) from patients with psoriasis and ulcerative colitis (UC) and of CRP (x), IL-6 (y) and TNF-α (z) from patients with chronic fatigue syndrome (CFS) displayed a separation between the B. infantis 35624 treated groups compared with the placebo treated groups. Results are expressed as the change from baseline (post-treatment minus pre-treatment level) for each patient.
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Figure 9.B. infantis 35624-feeding reduces pro-inflammatory cytokines levels from LPS stimulated PBMCs in healthy volunteers. In vitro LPS stimulated PBMCs displayed decreased secretion of IL-6 and TNF-α following B. infantis 35624 oral consumption (n = 10) for eight weeks. This finding was not observed in the placebo group (n = 12). Results are expressed as the change from baseline (post-treatment minus pre-treatment level) for each individual. *p < 0.05 vs. placebo group (Mann-Whitney U test).

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References

    1. Beutler B. Inferences, questions and possibilities in Toll-like receptor signalling. Nature. 2004;430:257–63. doi: 10.1038/nature02761. - DOI - PubMed
    1. Garrett WS, Gordon JI, Glimcher LH. Homeostasis and inflammation in the intestine. Cell. 2010;140:859–70. doi: 10.1016/j.cell.2010.01.023. - DOI - PMC - PubMed
    1. Lee YK, Menezes JS, Umesaki Y, Mazmanian SK. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2011;108(Suppl 1):4615–22. doi: 10.1073/pnas.1000082107. - DOI - PMC - PubMed
    1. Wu HJ, Ivanov II, Darce J, Hattori K, Shima T, Umesaki Y, et al. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity. 2010;32:815–27. doi: 10.1016/j.immuni.2010.06.001. - DOI - PMC - PubMed
    1. Atarashi K, Tanoue T, Shima T, Imaoka A, Kuwahara T, Momose Y, et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science. 2011;331:337–41. doi: 10.1126/science.1198469. - DOI - PMC - PubMed

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