A fermented formula may reduce the severity of acute diarrhea among healthy young infants. This outcome may be linked to the bifidogenic effects of fermentation products and their interactions with the intestinal immune system.

Background/Objectives: To determine the impact of a not hydrolyzed fermented infant formula containing heat-killed Bifidobacterium breve C50 and Streptococcus thermophilus 065 (HKBBST) on the incidence of allergy-like events during the first 2 years of life in children at high risk of atopy. Subjects/Methods: This multicenter, randomized, double-blind, controlled study included infants at high risk of atopy. Infants used HKBBST or a standard infant formula (SIF) since birth until 1 year of age, and were followed at 4, 12 and 24 months after birth. Skin prick tests (SPTs) for six foods and six aeroallergens were systematically performed and adverse events (AEs) were recorded. In case of potentially allergic AE (PAAE), allergy could be further tested by SPT, patch tests and quantification of specific IgEs. If cow's milk allergy (CMA) was suspected, an oral challenge could also be performed. Results: The study included 129 children, 63 were randomized to SIF, 66 to HKBBST. The use of HKBBST milk did not alter the proportion of CMA but decreased the proportion of positive SPT to cow's milk (1.7 vs 12.5%, P ¼ 0.03), and the incidence of digestive (39 vs 63%, P ¼ 0.01) and respiratory potentially allergic AEs (7 vs 21%, P ¼ 0.03) at 12 months, and that of respiratory PAAEs at 24 months (13 vs 35%, P ¼ 0.01). Conclusions: HKBBST decreased the incidence of PAAEs in children with family history of atopy, during the first months of life and after the formula was stopped. Oral tolerance to cow's milk in infants at high risk of atopy may therefore be improved using not hydrolyzed fermented formulae.

BackgroundProbiotic bacteria have been shown to modulate immune responses and could have therapeutic effects in allergic and inflammatory disorders. However, the signaling pathways engaged by probiotics are poorly understood. We have previously reported that a fermentation product from Bifidobacterium breve C50 (BbC50sn) could induce maturation, high IL-10 production and prolonged survival of DCs via a TLR2 pathway. We therefore studied the roles of mitogen-activated protein kinases (MAPK), glycogen synthase kinase-3 (GSK3) and phosphatidylinositol 3-kinase (PI3K) pathways on biological functions of human monocyte-derived DCs treated with BbC50sn.Methodology/Principal FindingsDCs were differentiated from human monocytes with IL-4 and GM-CSF for 5 days and cultured with BbC50sn, lipopolysaccharide (LPS) or Zymosan, with or without specific inhibitors of p38MAPK (SB203580), ERK (PD98059), PI3K (LY294002) and GSK3 (SB216763). We found that 1) the PI3K pathway was positively involved in the prolonged DC survival induced by BbC50sn, LPS and Zymosan in contrast to p38MAPK and GSK3 which negatively regulated DC survival; 2) p38MAPK and PI3K were positively involved in DC maturation, in contrast to ERK and GSK3 which negatively regulated DC maturation; 3) ERK and PI3K were positively involved in DC-IL-10 production, in contrast to GSK3 that was positively involved in DC-IL-12 production whereas p38MAPK was positively involved in both; 4) BbC50sn induced a PI3K/Akt phosphorylation similar to Zymosan and a p38MAPK phosphorylation similar to LPS.Conclusion/SignificanceWe report for the first time that a fermentation product of a bifidobacteria can differentially activate MAPK, GSK3 and PI3K in order to modulate DC biological functions. These results give new insights on the fine-tuned balance between the maintenance of normal mucosal homeostasis to commensal and probiotic bacteria and the specific inflammatory immune responses to pathogen bacteria.

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