BackgroundWe previously showed that evaluation of anti-inflammatory activities of lactic acid bacteria in porcine intestinal epithelial (PIE) cells is useful for selecting potentially immunobiotic strains.ObjectiveThe aims of the present study were: i) to select potentially immunomodulatory bifidobacteria that beneficially modulate the Toll-like receptor (TLR)-4-triggered inflammatory response in PIE cells and; ii) to gain insight into the molecular mechanisms involved in the anti-inflammatory effect of immunobiotics by evaluating the role of TLR2 and TLR negative regulators in the modulation of proinflammatory cytokine production and activation of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways in PIE cells.Results
Bifidobacteria longum BB536 and B. breve M-16V strains significantly downregulated levels of interleukin (IL)-8, monocyte chemotactic protein (MCP)-1 and IL-6 in PIE cells challenged with heat-killed enterotoxigenic Escherichia coli. Moreover, BB536 and M-16V strains attenuated the proinflammatory response by modulating the NF-κB and MAPK pathways. In addition, our findings provide evidence for a key role for the ubiquitin-editing enzyme A20 in the anti-inflammatory effect of immunobiotic bifidobacteria in PIE cells.ConclusionsWe show new data regarding the mechanism involved in the anti-inflammatory effect of immunobiotics. Several strains with immunoregulatory capabilities used a common mechanism to induce tolerance in PIE cells. Immunoregulatory strains interacted with TLR2, upregulated the expression of A20 in PIE cells, and beneficially modulated the subsequent TLR4 activation by reducing the activation of MAPK and NF-κB pathways and the production of proinflammatory cytokines. We also show that the combination of TLR2 activation and A20 induction can be used as biomarkers to screen and select potential immunoregulatory bifidobacteria strains.
These data suggest that the prenatal and postnatal supplementation of bifidobacteria is effective in primary preventing allergic diseases. Some limited changes in the composition of fecal microbiota by the bifidobacterial supplementation were observed.
Accumulating evidence suggests a relationship between the gut microbiota and the development of obesity, indicating the potential of probiotics as a therapeutic approach.
Bifidobacterium breve B-3 has been shown to exert anti-obesity effects in high-fat diet-induced obese mice. In the present study, the anti-obesity effects of the
consumption of B. breve B-3 by healthy pre-obese (25 ≤ BMI < 30) adults were investigated in a randomized, double-blind, placebo-controlled trial (trial registration:
UMIN-CTR No. 000023919; preregistered on September 2, 2016). Eighty participants were randomized to receive placebo or B. breve B-3 capsules (2 × 1010 CFU/day)
daily for 12 weeks. The visceral fat area significantly increased at weeks 4 and 8 in the placebo group only; no significant change was observed in the B-3 group. Body fat mass and percent
body fat were significantly lower in the B-3 group than in the placebo group at weeks 8 and 12 (p<0.05, ANCOVA adjusted with baseline values). Although no significant differences were
observed in blood parameters between the groups, the intake of B. breve B-3 slightly decreased triglyceride levels and improved HDL cholesterol from the baseline. No serious
adverse effects were noted in either group. These results suggest that the probiotic strain B. breve B-3 has potential as a functional food ingredient to reduce body fat in
healthy pre-obese individuals.
In this work, we aimed to characterize the antiviral response of an originally established porcine intestinal epithelial cell line (PIE cells) by evaluating the molecular innate immune response to rotavirus (RVs). In addition, we aimed to select immunomodulatory bacteria with antiviral capabilities. PIE cells were inoculated with RVs isolated from different host species and the infective titers and the molecular innate immune response were evaluated. In addition, the protection against RVs infection and the modulation of immune response by different lactic acid bacteria (LAB) strains was studied. The RVs strains OSU (porcine) and UK (bovine) effectively infected PIE cells. Our results also showed that RVs infection in PIE cells triggered TLR3-, RIG-I- and MDA-5-mediated immune responses with activation of IRF3 and NF-κB, induction of IFN-β and up-regulation of the interferon stimulated genes MxA and RNase L. Among the LAB strains tested, Bifidobacterium infantis MCC12 and B. breve MCC1274 significantly reduced RVs titers in infected PIE cells. The beneficial effects of both bifidobacteria were associated with reduction of A20 expression, and improvements of IRF-3 activation, IFN-β production, and MxA and RNase L expressions. These results indicate the value of PIE cells for studying RVs molecular innate immune response in pigs and for the selection of beneficial bacteria with antiviral capabilities.
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