Safety of high doses of Propionibacterium freudenreichii ET-3 culture in healthy adult subjects.

Propionibacterium freudenreichii ET-3 (7025) culture, a cell-free product of whey fermentation by P. freudenreichii ET-3, has been shown to promote the growth of Bifidobacteria through the action of 1,4-dihydroxy-2-naphthoic acid (DHNA). Here we report the results of two clinical studies designed to evaluate the safety of high doses of P. freudenreichii ET-3 culture medium. Study 1 had a randomized, double-blind, crossover design. Ten healthy male and four healthy female subjects received 45 tablets of either P. freudenreichii ET-3 culture medium (total daily intake of 3g solid content and 283.5µg of DHNA; active group) or placebo (unfermented product) during two 1-week supplementation periods separated by a 4-week washout period. In Study 2, 11 healthy men took four tablets of P. freudenreichii ET-3 culture medium per day (total daily intake of 0.267g solid content and 22.5µg of DHNA) for a period of 13weeks. In both studies, hematological, clinical chemistry, and urinary parameters were measured before and after each supplementation period and gastrointestinal symptoms were assessed by questionnaire. In Study 1, there were no statistically significant differences between placebo and active supplementation periods in any measured parameter and the incidence of gastrointestinal symptoms were similar between groups. In Study 2, total protein, white blood cell count, hemoglobin, and mean corpuscular hemoglobin concentration decreased significantly from baseline and mean corpuscular volume and urine pH increased from baseline. The changes in hematological parameters were deemed not to be due to P. freudenreichii ET-3 culture medium supplementation given that all parameters remained within normal ranges and were not consistent with any clinically meaningful effect.

Recognition of T cell epitopes unique to Cha o 2, the major allergen in Japanese cypress pollen, in allergic patients cross-reactive to Japanese cedar and Japanese cypress pollen.

BACKGROUND: Pollens from species of the Cupressaceae family are one of the most important causes of respiratory allergies worldwide. Many patients with pollinosis have specific IgE to both allergens from Japanese cedar and Japanese cypress pollen. We set out to identify T cell epitopes in Cha o 2, the second major allergen of Japanese cypress pollen. METHODS: T cell lines (TCL) and T cell clones (TCC) specific to Cha o 2 were generated from allergic patients cross-reactive to Japanese cedar and Japanese cypress pollen. T cell epitopes in Cha o 2 were identified by responses of TCL stimulated with overlapping peptides. Abilities of IL-4/IFN-gamma production by TCC were evaluated using enzyme immunoassay. RESULTS: Using TCL, 11 dominant and subdominant T cell epitopes were identified in Cha o 2. The subsets of TCC were predominantly of T helper 2-type. A T cell epitope p141-160 in Cha o 2 and corresponding peptide in Cry j 2 showed high homology. Although TCC PC.205.159 responded to stimulation with p141-160 in Cha o 2, it did not respond with corresponding peptide in Cry j 2, therefore, the T cell epitope was unique to Cha o 2. CONCLUSIONS: Eleven T cell epitopes that were identified are unique to Cha o 2. Cha o 2 is a putative aeroallergen that can potentially sensitize human T cells. We concluded that generation of T cells specific to Cha o 2 in allergic patients acts as one of the causes of continuous allergic symptoms in April.

Inhibitory effects of Bifidobacterium longum on experimental ulcerative colitis induced in mice by synthetic dextran sulfate sodium.

BACKGROUND/AIMS: The relationship between alterations in intestinal microflora and ulcerative colitis is still not clear. Whether improvement in bacterial populations might be a new strategy for prevention or treatment needs to be tested. METHODS: Ulcerative colitis was induced in mice by oral administration of synthetic dextran sulfate sodium (molecular weight 54,000). Inhibitory effects of concomitant treatment with Bifidobacterium longum were assessed in terms of total colon length and severity of histological changes. In addition, changes of microflora and short-chain fatty acids were tested in fecal samples and compared before and after treatment. RESULTS: Administration of B. longum significantly inhibited both shortening of total colon length and the severity of ulcerative colitis compared to controls. It was confirmed that the administered B. longum resided in the gut and blocked the decrease of lactobacilli in fecal samples in mice with dextran sulfate sodium-induced colitis. CONCLUSIONS: Oral administration of B. longum exerts marked inhibitory effects on ulcerative colitis in mice.