Consumption of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 augments serum antibody titers against seasonal influenza vaccine in healthy adults.

Seasonal influenza is a major upper respiratory tract infection occurring in winter. Vaccination is the best method for preventing this infection. We conducted two randomized, double-blind, placebo-controlled trials to examine whether consumption of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1, which has been reported to reduce the risk of catching the common cold, augments serum antibody titers against seasonal influenza vaccines. In the first trial, which included university students, serum antibody titers against influenza A (H3N2) and B viruses were significantly higher in the yogurt group than in the placebo group. According to the guidelines established by the European Medicines Agency (EMA) for the assessment of vaccines, the seroconversion rate and mean geometric increase of influenza A (H3N2) and seroprotection of influenza B met the criteria only in the yogurt group. In the second trial, which included healthy adults, serum antibody titers against influenza A (H1N1) and B viruses were significantly higher in the yogurt group than in the placebo group. The seroconversion rate and mean geometric increase of influenza B met the EMA criteria only in the yogurt group. Furthermore, the cumulative days of ill health, such as throat complaints, upper respiratory inflammation, and cold, were significantly lower in the yogurt group than in the placebo group. Therefore, daily intake of yogurt fermented with L. bulgaricus OLL1073R-1 could reduce the duration of symptoms caused by respiratory infections and act as a mucosal adjuvant enhancing acquired immune responses against vaccines, leading to the improvement of public health.

Lactobacillus gasseri PA-3 reduces serum uric acid levels in patients with marginal hyperuricemia.

Several studies have reported that Lactobacillus gasseri PA-3 reduces the level of serum uric acid (SUA) in patients with hyperuricemia. However, it remains unknown how PA-3 affects uric acid metabolism. In the present study, we examined effects of PA-3-containing yoghurt on uric acid metabolism in patients with marginal hyperuricemia. Sixteen patients with SUA > 357 µmol/L (marginal hyperuricemia) were enrolled. PA-3-containing yoghurt was administered for 8 weeks. Uric acid metabolism was evaluated just before and 8 weeks after the administration and at 4 weeks after the administration ended (post-administration). SUA levels after the administration were significantly lower than that before the administration and remained low at post-administration. Urinary uric acid concentration (Uur) after the administration were significantly lower than that before the administration. However, post-administration Uur levels were comparable to those before the administration. Therefore, PA-3-containing yoghurt significantly reduced the levels of SUA and Uur in patients with marginal hyperuricemia.

Effects of Nelumbo nucifera Leaf Extract on Obesity.

The two main components from a Nelumbo nucifera leaf extract (NnEx) were investigated for their ability to prevent triglyceride accumulation and promoting lipolysis. Sun-dried Nelumbo nucifera leaves were immersed in hot water to extract the soluble components, and the resulting solution was analyzed by LC-MS and nuclear magnetic resonance. The results showed that quercetin-3-O-ß-glucuronide (Q3GA) and quercetin were the key components of the NnEx. In vitro experiments confirmed that quercetin and Q3GA functioned in lipid metabolism by promoting triglyceride degradation through inhibition of the cAMP pathway. In vivo experiments showed that NnEx ingestion inhibited the accumulation of neutral fats in ICR mice and transitioned the hepatocytes of type II diabetic KK-Ay mice out of glycogenosis. These results highlight the ability of NnEx to control metabolism by modulating fat and sugar absorption and may provide an interesting novel treatment for obesity and related lifestyle diseases such as type II diabetes.

Ingesting Yogurt Containing Lactobacillus plantarum OLL2712 Reduces Abdominal Fat Accumulation and Chronic Inflammation in Overweight Adults in a Randomized Placebo-Controlled Trial.

BACKGROUND: Chronic inflammation and insulin resistance are factors that are related to obesity. We have suggested that the administration of heat-treated Lactobacillus plantarum OLL2712 (OLL2712) cells can improve glucose and lipid metabolism by suppressing chronic inflammation in mouse models and a preliminary clinical study. OBJECTIVE: The aim of this study was to investigate whether ingesting OLL2712 cells can reduce body fat accumulation and improve metabolic risk factors, in overweight, healthy adults. METHODS: This study was a randomized, double-blind, placebo-controlled, parallel-group trial conducted at a single center in Japan. The study participants included 100 overweight (BMI range, ≥25 to <30 kg/m2) adults aged 20-64 y. They were randomly assigned to either the placebo or OLL2712 group (n = 50 each) and were administered conventional yogurt or yogurt containing >5 × 109 heat-treated OLL2712 cells, respectively, daily for 12 wk. The primary outcome was the 12-wk change in the abdominal fat area, as assessed by computed tomography, and the secondary outcomes were glucose and lipid metabolism-related parameters and chronic inflammation markers, which were analyzed using a linear mixed model. RESULTS: The 12-wk change of abdominal fat area (difference: 8.5 cm2; 95% CI: 0.3, 16.6 cm2; P = 0.040) and fasting plasma glucose (difference: 3.2 mg/dL; 95% CI: 0.8, 5.6 mg/dL; P = 0.021) were significantly less in the OLL2712 group than the placebo group. The overall trend of serum IL-6 was significantly decreased in the OLL2712 group compared with baseline and the placebo group. CONCLUSIONS: The ingestion of heat-treated OLL2712 cells reduces body fat accumulation and the deterioration of glycemic control and chronic inflammation, in overweight, healthy adults. We hypothesize that OLL2712 cells may prevent obesity by regulating chronic inflammation. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry as UMIN000027709.

Exopolysaccharides from milk fermented by lactic acid bacteria enhance dietary carotenoid bioavailability in humans in a randomized crossover trial and in rats.

BACKGROUND: Dietary supplementation with carotenoids can have beneficial health effects, but carotenoids are poorly absorbed. OBJECTIVES: We aimed to evaluate how milk fermented by lactic acid bacteria affects dietary carotenoid bioavailability in humans and rats and to investigate mechanisms by which active components in milk fermented by Lactobacilli enhance dietary carotenoid absorption. METHODS: Male rats (n = 8/group) were administered ß-carotene or ß-carotene + fermented milk. Rats (n = 6/group) were also pretreated with ezetimibe, a cholesterol absorption inhibitor, to investigate ß-carotene transport mechanisms. In humans, 3 studies were conducted using a randomized crossover method. Subjects (n = 16/study) consumed a vegetable (carrot, tomato, or spinach) drink alone or with a fermented milk drink. Blood samples were collected at various time points after consumption. RESULTS: In rats, the serum ß-carotene area under the concentration-time curve (AUC) was significantly higher for the ß-carotene + fermented milk than for ß-carotene only. A significant correlation (r = 0.83, P < 0.001) between the exopolysaccharide (EPS) content of fermented milk and serum ß-carotene AUC was observed. Ezetimibe treatment did not suppress elevations in serum ß-carotene concentrations induced by fermented milk ingestion. In humans, the incremental area under the concentration-time curve (iAUC) for ß-carotene in the plasma triacylglycerol-rich lipoprotein (TRL) fraction was significantly (1.8-fold, range: 0.6-3.9) higher when carrot + fermented milk was consumed compared with carrot drink alone. A significantly (6.5-fold, range: 0.04-7.7) higher iAUC for lycopene in the plasma TRL fraction was observed for subjects who consumed tomato + fermented milk compared with tomato drink alone. A significant increase in plasma lutein in all fractions was observed after consumption of spinach + fermented milk, but not with spinach drink alone. CONCLUSIONS: Co-ingestion of ß-carotene and fermented milk significantly increased dietary ß-carotene bioavailability in humans and rats. EPSs could affect the physical properties of fermented milk to enhance dietary ß-carotene absorption mediated by simple diffusion mechanisms. These findings may be relevant for methods to increase dietary carotenoid bioavailability.This trial was registered at umin.ac.jp/ctr as UMIN000034838, UMIN000034839, and UMIN000034840.

Effects of 12-Week Ingestion of Yogurt Containing Lactobacillus plantarum OLL2712 on Glucose Metabolism and Chronic Inflammation in Prediabetic Adults: A Randomized Placebo-Controlled Trial.

The ingestion of Lactobacillus plantarum OLL2712 (OLL2712) cells improved glucose metabolism by suppressing chronic inflammation in mouse models and in a preliminary clinical study. We aimed to clarify the effect of OLL2712 on glucose metabolism and chronic inflammation for healthy adults. Prediabetic adults (n = 130, age range: 20-64 years) were randomly assigned to either the placebo or OLL2712 groups (n = 65 each) and were administered conventional yogurt or yogurt containing more than 5 × 109 heat-treated OLL2712 cells, respectively, daily for 12 weeks. Reduced HbA1c levels after 12 weeks of treatment were observed in both groups compared to those at baseline; however, the 12-week reduction of HbA1c levels was significantly greater in the OLL2712 group than in the placebo group. Increased chronic inflammation marker levels and insulin-resistant index (HOMA-IR) occurred in the placebo group but not in the OLL2712 group. Fasting blood glucose (FBG) levels did not change significantly in both groups; however, in subgroup analyses including participants with higher FBG levels, FBG levels were significantly reduced only in the OLL2712 group compared to baseline. These results suggest that OLL2712 cell ingestion can reduce HbA1c levels and can prevent the aggravation of chronic inflammation and insulin resistance.

Probiotic L. gasseri strain (LG21) for the upper gastrointestinal tract acting through improvement of indigenous microbiota.

OBJECTIVE: To describe probiotics including a Lactobacillus gasseri strain LG21 used for the upper gastrointestinal tract, which are considered to act through improvement of indigenous microbiota inhabiting there. BACKGROUND AND DESIGN: Because the early definition of probiotics emphasized their effects on improving the intestinal microbial ecology, their effects on the intestinal tract and its immunity have been considered common general benefits associated with probiotics. This conclusion was also based on a body of successful clinical trials whose endpoints were the prevention or treatment of intestinal diseases. In contrast to intestinal microbiota, our understanding of the role of gastric microbiota in human health and physiology remains poor, as the bacterial load in the stomach is considered too small to exert a significant effect due to the highly acidic environment of the human stomach. Therefore, the intervention using probiotics in the stomach is still limited at present.Results:In this article using representative 38 quoted articles, we first describe the gastric microbiota, as the indigenous microbiota in the stomach is thought to be significantly involved in the pathophysiology of this organ, since probiotics exert their beneficial effects through improving the resident microbiota. We then review the present status and future prospects of probiotics for the treatment of upper gastrointestinal diseases by quoting representative published articles, including our basic and clinical data. CONCLUSIONS: Probiotics have been demonstrated to suppress Helicobacter pylori in the stomach, and are also expected to improve functional dyspepsia through the correction of dysbiotic gastric microbiota.

Effect of ingesting yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 on influenza virus-bound salivary IgA in elderly residents of nursing homes: a randomized controlled trial.

Objective: The purpose of this study was to clarify the influence of consuming yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (1073R-1-yogurt) on influenza virus-bound salivary immunoglobulin A (IgA) levels, in the elderly residents of nursing homes. Methods: A double-blind, parallel-group, randomized controlled trial was conducted with 96 elderly volunteers residing in 2 nursing homes. During the trial, participants consumed 100 g of 1073R-1-yogurt every morning for 12 weeks, whereas the control participants consumed yogurt fermented with a different Lactobacillus strain (control yogurt). Saliva was collected before the trial and after 4, 8 and 12 weeks of yogurt ingestion. Results: Our data indicated that consumption of 1073R-1-yogurt affected influenza A virus subtype H3N2-bound IgA levels in saliva (p = .001). In addition, saliva flow rate and total IgA levels increased in response to the yogurt intake period in both the 1073R-1 and control yogurt groups (p = .04). Conclusions: Our study suggests that continuous daily ingestion of 1073R-1-yogurt may help prevent infection with influenza A virus subtype H3N2 in elderly subjects with weakened immunity, by increasing the production of influenza A virus subtype of H3N2-bound salivary IgA.

Hypouricaemic effects of yoghurt containing Lactobacillus gasseri PA-3 in patients with hyperuricaemia and/or gout: A randomised, double-blind, placebo-controlled study.

PURPOSE: Lactobacillus gasseri PA-3 (PA-3) has been previously shown to decrease serum uric acid (SUA) levels in subjects with increased SUA. In this study, we investigated whether PA-3 is also capable of decreasing SUA levels in patients with hyperuricaemia and/or gout. METHODS: Twenty-five patients with hyperuricaemia and/or gout completed this study. Urate-lowering drugs were discontinued for 12 weeks (week -4 to week 8). After flushing of urate-lowering drugs for 4 weeks (week 0), patients were randomised equally to receive diets containing yoghurt beverages with PA-3 or without PA-3 for a duration of 8 weeks (week 8). The intention to treat (ITT) population included all subjects who were randomised, and the per-protocol (PP) population included subjects who completed the experiment with compliance. We evaluated SUA levels at the end of the study as well as changes in SUA levels in comparison to week 0. RESULTS: In both ITT and PP analyses, there were no significant differences in SUA levels or in the changes in SUA levels compared to week 0 between the two groups. However, in a sub-population whose SUA levels at week 0 were within one SD of the mean of the whole PP population, changes in SUA levels in the group consuming PA-3-containing yoghurt were significantly lower than those of the control group (p = .0378). CONCLUSION: PA-3-containing yoghurt improves SUA levels, even in patients with hyperuricaemia and/or gout.

Antibiotics suppress colon tumorigenesis through inhibition of aberrant DNA methylation in an azoxymethane and dextran sulfate sodium colitis model.

Chronic inflammation is involved in the development of colon cancer by inducing mutations and aberrant DNA methylation in colon epithelial cells. Furthermore, there is growing evidence that colonic microbiota modulates the inflammation response in the host and influences colon tumorigenesis. However, the influence of colonic microbiota on aberrant DNA methylation remains unknown. Here, we show the effect of colonic microbes on DNA methylation and tumorigenicity using a mouse model of human ulcerative colitis. Mice treated with azoxymethane (AOM) and dextran sulfate sodium (DSS) showed an increase in degree of colitis, as estimated by body weight, occult blood, and stool consistency/diarrhea at 2 weeks after treatment, but treatment with antibiotics markedly reduced the severity of the colitis. Although mucosal hyperplasia and increased inflammation-related genes were observed in the colonic epithelial cells of the AOM/DSS-treated mice, treatment with antibiotics abrogated these changes. In addition, treatment with antibiotics significantly decreased the number of mucosal nodules from 5.9 ± 5.3 to 0.2 ± 0.6 (P < .01) and area of occupancy from 50.1 ± 57.4 to 0.5 ± 1.4 mm2 (P < .01). Aberrant DNA methylation of three marker CpG islands (Cbln4, Fosb, and Msx1) was induced by AOM/DSS treatment in colonic mucosae, but this increase was suppressed by 50%-92% (P < .05) with antibiotic treatment. Microbiome analysis showed that this change was associated with a decrease of the Clostridium leptum subgroup. These data indicate that antibiotics suppressed tumorigenesis through inhibition of aberrant DNA methylation induced by chronic inflammation.

Effects of 12-wk Lactobacillus plantarum OLL2712 treatment on glucose metabolism and chronic inflammation in prediabetic individuals: A single-arm pilot study.

OBJECTIVE: Previously, we demonstrated that the administration of heat-killed OLL2712 cells suppressed chronic inflammation and improved hyperglycemia in a mouse model of obesity and diabetes. The aim of this study was to preliminarily examine the effect of OLL2712 supplementation on glucose metabolism and chronic inflammation in prediabetic subjects. METHODS: This study was a prospective, 12-wk, single-arm, open trial, followed by a 4-wk posttreatment period. Inclusion criteria were fasting plasma glucose levels of 105 to 130 mg/dL in an age range of 35 to 65 y. Thirty individuals consumed a dairy beverage containing ∼1 × 1010 heat-killed OLL2712 cells for 12 wk. RESULTS: The ingestion of the OLL2712 beverage significantly improved fasting plasma glucose levels, serum glycoalbumin levels, and insulin resistance indexes compared with baseline levels. The intervention also suppressed serum monocyte chemotactic protein-1 and interleukin-6 levels, which are proinflammatory cytokines involved in the development of insulin resistance and hyperglycemia. Furthermore, stratified analysis by these proinflammatory cytokine levels revealed that the beneficial effects of OLL2712 beverage were observed particularly in individuals with chronic inflammation at baseline. CONCLUSION: The results of this study suggested that heat-killed OLL2712 cells have the potential to improve insulin resistance and glucose metabolism by suppressing chronic inflammation.

Anti-Fatigue Effects of Yogurt Fermented with Lactobacillus delbureckii subsp. bulgaricus OLL1073R-1 in Healthy People Suffering from Summer Heat Fatigue: A Randomized, Double-Blind, Placebo-Controlled Trial.

Fatigue caused by summer heat is a typical indefinite complaint along with anorexia, loss of sleep, stress, lack of motivation and, in some cases, catching a cold. Yogurt fermented with Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 has been shown to stimulate the immune system and reduce the risk of catching colds. Here, we conducted a randomized, double-blinded, placebo-controlled trial to investigate whether ingesting this yogurt could ameliorate summer heat fatigue in 49 healthy males (median age 40.0 ± 6.0 years; 30⁻49 years) who felt fatigued every summer. Fatigue was evaluated by visual analogue scales (VAS) and the balance of sympathetic/parasympathetic nervous systems. After 12 weeks of ingestion in early autumn, the VAS fatigue scores in the yogurt group were lower than those of the placebo group. These results indicate that yogurt fermented with L. bulgaricus OLL1073R-1 can ameliorate summer heat fatigue lasting up to early autumn.

Effects of long-term intake of a yogurt fermented with Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 on mice.

The gut is an extremely complicated ecosystem where micro-organisms, nutrients and host cells interact vigorously. Although the function of the intestine and its barrier system weakens with age, some probiotics can potentially prevent age-related intestinal dysfunction. Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131, which are the constituents of LB81 yogurt, are representative probiotics. However, it is unclear whether their long-term intake has a beneficial influence on systemic function. Here, we examined the gut microbiome, fecal metabolites and gene expression profiles of various organs in mice. Although age-related alterations were apparent in them, long-term LB81 yogurt intake led to an increased Bacteroidetes to Firmicutes ratio and elevated abundance of the bacterial family S24-7 (Bacteroidetes), which is known to be associated with butyrate and propanoate production. According to our fecal metabolite analysis to detect enrichment, long-term LB81 yogurt intake altered the intestinal metabolic pathways associated with propanoate and butanoate in the mice. Gene ontology analysis also revealed that long-term LB81 yogurt intake influenced many physiological functions related to the defense response. The profiles of various genes associated with antimicrobial peptides-, tight junctions-, adherens junctions- and mucus-associated intestinal barrier functions were also drastically altered in the LB81 yogurt-fed mice. Thus, long-term intake of LB81 yogurt has the potential to maintain systemic homeostasis, such as the gut barrier function, by controlling the intestinal microbiome and its metabolites.

Lactobacillus gasseri PA-3 Uses the Purines IMP, Inosine and Hypoxanthine and Reduces their Absorption in Rats.

Excessive intake of purine-rich foods elevates serum levels of uric acid. Animal and fish meats contain high amounts of inosine and its related purines, and the reduction of taking those purines is crucial for the improvement of serum uric acid levels. We previously showed that Lactobacillus gasseri PA-3 (PA-3) incorporates adenosine and its related purines and that oral treatment with PA-3 reduced adenosine absorption in rats. This study investigated whether PA-3 also incorporates IMP (inosine 5'-monophosphate), inosine, and hypoxanthine, and whether it reduces their absorption in rats. PA-3 was incubated in vitro with radioisotope (RI)-labeled IMP, inosine, and hypoxanthine, and the incorporation of these compounds by PA-3 was evaluated. In addition, rats were orally administered PA-3 along with RI-labeled inosine 5'-monophosphate, inosine, or hypoxanthine, and the ability of PA-3 to attenuate the absorption of these purines was determined. PA-3 incorporated all three purines and displayed greater proliferation in the presence than in the absence of these purines. Oral administration of PA-3 to rats reduced the absorption of IMP, inosine, and hypoxanthine. These results indicate that PA-3 reduces the absorption of purines contained in foods and it is expected that PA-3 contributes attenuation of the excessive intake of dietary purines.

Yogurt Containing Lactobacillus gasseri Mitigates Aspirin-Induced Small Bowel Injuries: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Although there is evidence about the beneficial effects of probiotics, their effects on aspirin-induced small bowel injuries have not been well examined. We evaluated the effects of the probiotic Lactobacillus gasseri OLL2716 (LG) on aspirin-induced small intestinal lesions, such as ulcers, erosions, reddened lesions, and bleeding. SUMMARY: This study enrolled 64 patients who received aspirin for more than 1 month and provided written informed consent to be part of the study. The patients received 112 ml of yogurt containing LG or placebo twice daily for 6 weeks. Small bowel injuries were evaluated by capsule endoscopy before and after consuming the yogurt. The effect of LG on patient symptoms was also assessed using the Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (FSSG) and Gastrointestinal Symptom Rating Scale (GSRS) questionnaires before and after 6 weeks of treatment. There was no significant difference in any baseline characteristics and the number of small bowel mucosal breaks between the 2 groups. In contrast with the placebo group, the LG group had significantly fewer small bowel mucosal breaks and reddened lesions after 6 weeks (p < 0.01). The FSSG and GSRS scores were also significantly improved in the LG group but not in the placebo group. Key Messages: This double-blind, placebo-controlled study found that LG may be useful in reducing aspirin-induced small bowel injuries and in mitigating gastrointestinal symptoms.

Enhanced natural killer cell activation by exopolysaccharides derived from yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1.

Yogurt is generally recognized as a beneficial food for our health, but research into its physiological effects has focused mainly on intestinal dysfunctions such as constipation and diarrhea. We previously found yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (hereafter OLL1073R-1) could reduce risks of catching the common cold and flu in human trials. It was assumed that immunostimulatory exopolysaccharide (EPS) produced from OLL1073R-1 play an important role in this context. However, few studies have examined the immunostimulatory effects of traditional Bulgarian yogurts fermented with different strains of lactobacilli and their metabolites. Therefore, we screened 139 L. delbrueckii ssp. bulgaricus strains and identified OLL1073R-1 as the most robust producer of EPS. This strain was also the only strain that induced the production of IFN-γ in vitro. Oral administration of the EPS or yogurt fermented with OLL1073R-1 and Streptococcus thermophilus OLS3059 (OLL1073R-1 yogurt) augmented natural killer (NK) cell activity and induced IFN-γ production in spleen cells in mice, whereas 2 other yogurts fermented with other strains had no effect on NK cell activity. Cellular preparations of the OLL1073R-1 strain also slightly augmented NK cell activity, but were less effective than EPS itself. The EPS-dependent stimulation of NK cell activity was abrogated in IFN-γ knockout mice and in myeloid differentiation factor 88 knockout mice. Furthermore, IFN-γ production from spleen cells stimulated with EPS was completely blocked with both anti-IL-12 and anti-IL-18 antibodies in vitro. These findings suggest that NK cell activation by OLL1073R-1 yogurt is EPS-dependent, occurs via IL-12- and IL-18-mediated IFN-γ production, and requires myeloid differentiation factor 88. We showed that traditional Bulgarian yogurt could exert immunostimulatory effects by selecting starter strains and part of the mechanisms depend on IFN-γ inducible EPS produced from L. delbrueckii ssp. bulgaricus. Further investigations on processes of fermentation to increase of the EPS may lead to the development of new functional foods that keep our immune functions stable.

Dietary Milk Sphingomyelin Prevents Disruption of Skin Barrier Function in Hairless Mice after UV-B Irradiation.

Exposure to ultraviolet-B (UV-B) irradiation causes skin barrier defects. Based on earlier findings that milk phospholipids containing high amounts of sphingomyelin (SM) improved the water content of the stratum corneum (SC) in normal mice, here we investigated the effects of dietary milk SM on skin barrier defects induced by a single dose of UV-B irradiation in hairless mice. Nine week old hairless mice were orally administrated SM (146 mg/kg BW/day) for a total of ten days. After seven days of SM administration, the dorsal skin was exposed to a single dose of UV-B (20 mJ/cm2). Administration of SM significantly suppressed an increase in transepidermal water loss and a decrease in SC water content induced by UV-B irradiation. SM supplementation significantly maintained covalently-bound ω-hydroxy ceramide levels and down-regulated mRNA levels of acute inflammation-associated genes, including thymic stromal lymphopoietin, interleukin-1 beta, and interleukin-6. Furthermore, significantly higher levels of loricrin and transglutaminase-3 mRNA were observed in the SM group. Our study shows for the first time that dietary SM modulates epidermal structures, and can help prevent disruption of skin barrier function after UV-B irradiation.

A novel mechanism for improvement of dry skin by dietary milk phospholipids: Effect on epidermal covalently bound ceramides and skin inflammation in hairless mice.

BACKGROUND: Dietary milk phospholipids (MPLs) increase hydration of the stratum corneum and reduced transepidermal water loss (TEWL) in hairless mice fed a standard diet. However, the mechanism by which MPLs improve skin barrier functions has yet to be established. OBJECTIVE: This study was designed to examine the mechanism by which MPLs may affect covalently bound ceramides and markers of skin inflammation and improve the skin barrier defect in hairless mice fed a magnesium-deficient (HR-AD) diet. METHODS: Four-week-old female hairless mice were randomized into four groups (n=10/group), and fed a standard (control) diet, the HR-AD diet, the HR-AD diet supplemented with either 7.0 g/kg MPLs (low [L]-MPL) or 41.0 g/kg MPLs (high [H]-MPL). RESULTS: Dietary MPLs improved the dry skin condition of hairless mice fed the HR-AD diet. MPLs significantly increased the percentage of covalently bound ω-hydroxy ceramides in the epidermis, and significantly decreased both thymus and activation-regulated chemokine (TARC) mRNA and thymic stromal lymphopoietin (TSLP) mRNA levels in skin, compared with the HR-AD diet. Furthermore, the MPL diets significantly decreased serum concentrations of immunoglobulin-E, TARC, TSLP, and soluble P-selectin versus the HR-AD diet. CONCLUSION: Our study showed for the first time that dietary MPLs may modulate epidermal covalently bound ceramides associated with formation of lamellar structures and suppress skin inflammation, resulting in improved skin barrier function.

Role of indigenous lactobacilli in gastrin-mediated acid production in the mouse stomach.

It is known that the stomach is colonized by indigenous lactobacilli in mice. The aim of this study was to examine the role of such lactobacilli in the development of the stomach. For a DNA microarray analysis, germ-free BALB/c mice were orally inoculated with 10(9) CFU lactobacilli, and their stomachs were excised after 10 days to extract RNA. As a result, lactobacillus-associated gnotobiotic mice showed dramatically decreased expression of the gastrin gene in comparison to germ-free mice. The mean of the log(2) fold change in the gastrin gene was -4.3. Immunohistochemistry also demonstrated the number of gastrin-positive (gastrin(+)) cells to be significantly lower in the lactobacillus-associated gnotobiotic mice than in the germ-free mice. However, there was no significant difference in the number of somatostatin(+) cells in these groups of mice. Consequently, gastric acid secretion also decreased in the mice colonized by lactobacilli. In addition, an increase in the expression of the genes related to muscle system development, such as nebulin and troponin genes, was observed in lactobacillus-associated mice. Moreover, infection of germ-free mice with Helicobacter pylori also showed the down- and upregulation of gastrin and muscle genes, respectively, in the stomach. These results thus suggested that indigenous lactobacilli in the stomach significantly affect the regulation of gastrin-mediated gastric acid secretion without affecting somatostatin secretion in mice, while H. pylori also exerts such an effect on the stomach.