Tuula Tuure

Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a double-blind placebo-controlled trial

Background:  Probiotic bacteria are suggested to reduce symptoms of the atopic eczema/dermatitis syndrome (AEDS) in food‐allergic infants. We aimed to investigate whether probiotic bacteria have any beneficial effect on AEDS.

Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort.

BACKGROUND Less microbial exposure in early childhood is associated with more allergic disease later. Allergic children have a different fecal microflora, with less lactobacilli and bifidobacteria. Beneficial effects regarding the development of allergy have been suggested to come through probiotic supplementation. OBJECTIVE We sought to study the effect of probiotic and prebiotic supplementation in preventing allergies. METHODS In a double-blinded, placebo-controlled study we randomized 1223 mothers with infants at high risk for allergy to receive a probiotic mixture (2 lactobacilli, bifidobacteria, and propionibacteria) or placebo during the last month of pregnancy and their infants to receive it from birth until age 6 months. Infants also received a prebiotic galacto-oligosaccharide or placebo. At 5 years, we evaluated the cumulative incidence of allergic diseases (eczema, food allergy, allergic rhinitis, and asthma) and IgE sensitization. RESULTS Of the 1018 intent-to-treat infants, 891 (88%) attended the 5-year visit. Frequencies of allergic and IgE-associated allergic disease and sensitization in the probiotic and placebo groups were similar: 52.6% versus 54.9% and 29.5% versus 26.6%, respectively, and 41.3% in both. No significant difference appeared in frequencies of eczema (39.3% vs 43.3%), atopic eczema (24.0% vs 25.1%), allergic rhinitis (20.7% vs 19.1%), or asthma (13.0% vs 14.1%) between groups. However, less IgE-associated allergic disease occurred in cesarean-delivered children receiving probiotics (24.3% vs 40.5%; odds ratio, 0.47; 95% CI, 0.23% to 0.96%; P = .035). CONCLUSIONS No allergy-preventive effect that extended to age 5 years was achieved with perinatal supplementation of probiotic bacteria to high-risk mothers and children. It conferred protection only to cesarean-delivered children.

Long-Term Safety and Impact on Infection Rates of Postnatal Probiotic and Prebiotic (Synbiotic) Treatment: Randomized, Double-Blind, Placebo-Controlled Trial

OBJECTIVE. Live probiotic bacteria and dietary prebiotic oligosaccharides (together termed synbiotics) increasingly are being used in infancy, but evidence of long-term safety is lacking. In a randomized, placebo-controlled, double-blind trial, we studied the safety and long-term effects of feeding synbiotics to newborn infants. METHODS. Between November 2000 and March 2003, pregnant mothers carrying infants at high risk for allergy were randomly assigned to receive a mixture of 4 probiotic species (Lactobacillus rhamnosus GG and LC705, Bifidobacterium breve Bb99, and Propionibacterium freudenreichii ssp shermanii) or a placebo for 4 weeks before delivery. Their infants received the same probiotics with 0.8 g of galactooligosaccharides, or a placebo, daily for 6 months after birth. Safety data were obtained from clinical examinations and interviews at follow-up visits at ages 3, 6, and 24 months and from questionnaires at ages 3, 6, 12, and 24 months. Growth data were collected at each time point. RESULTS. Of the 1018 eligible infants, 925 completed the 2-year follow-up assessment. Infants in both groups grew normally. We observed no difference in neonatal morbidity, feeding-related behaviors (such as infantile colic), or serious adverse events between the study groups. During the 6-month intervention, antibiotics were prescribed less often in the synbiotic group than in the placebo group (23% vs 28%). Throughout the follow-up period, respiratory infections occurred less frequently in the synbiotic group (geometric mean: 3.7 vs 4.2 infections). CONCLUSION. Feeding synbiotics to newborn infants was safe and seemed to increase resistance to respiratory infections during the first 2 years of life.

Increased IFN-gamma secretion from duodenal biopsy samples in delayed-type cow's milk allergy.

A delayed and local gastrointestinal hypersensitivity to cows milk (CM) protein is difficult to diagnose and there are limited data on this disorder. The aim of this study was to investigate local intestinal cytokine secretion in the upper small intestine in children with delayed‐type cows milk allergy (CMA). Duodenal biopsy samples from 31 children with delayed CMA, 14 with celiac disease (CD), and 14 healthy controls were studied for the spontaneous release of IFN‐γ, TNF‐α, IL‐2, IL‐4, IL‐5, and IL‐10, measured by cytometric bead array, and of TGF‐β and IL‐6 measured by ELISA. The children with delayed CMA secreted more IFN‐γ than the controls (p = 0.006) and the children with CD (p = 0.006). The children with CD secreted more IL‐6 compared to the controls (p = 0.008) and the children with delayed CMA (p = 0.002). The children with delayed CMA who had continuously been exposed to CM secreted less TGF‐β than the children with delayed CMA who avoided CM (p = 0.050), and showed a tendency towards lower secretion compared to the controls (p = 0.078). Secretions of TNF‐α, IL‐2, IL‐4, IL‐5, and IL‐10 were low in general; however, the children with delayed CMA who did not avoid CM secreted more IL‐4 and IL‐10 than the controls (p = 0.016, 0.059). In conclusion, the children with delayed CMA showed up‐regulation of IFN‐γ. Interestingly, TGF‐β secretion was up‐regulated in those children with delayed CMA who avoided CM suggesting recovery of regulation mechanisms.

Effects of a fibre-enriched milk drink on insulin and glucose levels in healthy subjects

BackgroundThe glycaemic response to foods is dependent on the quality and content of carbohydrates. Carbohydrates in the form of dietary fibre have favourable effects on insulin and glucose metabolism and may help to control energy intake. Dairy products have a relatively low carbohydrate content, and most of the carbohydrate is in the form of lactose which causes gastrointestinal symptoms in part of the population. In order to avoid these symptoms, dairy products can be replaced with lactose-free dairy products which are on the market in many parts of the world. However, the effects of lactose-free products on insulin and glucose metabolism have not been studied.MethodsIn the present study, we investigated the effects of 1) a lactose-free milk drink, 2) a novel fibre-enriched, fat- and lactose-free milk drink and 3) normal fat-free milk on serum glucose and insulin levels and satiety using a randomized block design. Following an overnight fast, 26 healthy volunteers ingested 200 ml of one of these drinks on three non-consecutive days. Insulin and glucose levels and subjective satiety ratings were measured before the ingestion of the milk product and 20, 40, 60, 120 and 180 minutes after ingestion. The responses were calculated as the area under the curve subtracted by the baseline value (AUC minus baseline).ResultsThe insulin response was significantly lower for the fibre-enriched milk drink than it was for the other milk products (AUC, P = 0.007). There were no differences in the response for glucose or in the AUC for the subjective satiety ratings between the studied milk products.ConclusionThe present results suggest that this novel milk drink could have positive effects on insulin response.

Can primary hypolactasia manifest itself after the age of 20 years? A two-decade follow-up study

Objective. The age at manifestation of primary hypolactasia varies between ethnic groups. Many people report experiencing the first symptoms of lactose intolerance at adult age. The purpose of this study was to investigate whether primary hypolactasia can appear after the age of 20 among the Finnish population and to investigate the outcome of different diagnostic methods of lactose maldigestion. Material and methods. Lactose digestion status was assessed by the lactose tolerance test with ethanol (LTTE) in 42 subjects (38–71 years) who reported having gastrointestinal symptoms after the ingestion of 20 g or less of lactose and who were diagnosed as lactose digesters in earlier studies. Thirteen of the study subjects underwent upper gastrointestinal endoscopy, and 35 gave a blood sample for DNA analysis. Results. Only one of the 42 subjects studied had the genotype C/C−13910 indicating hypolactasia. Lactase activity was higher in those with the genotype T/T (69.2 U/g protein) than in those with the heterozygous genotype C/T (36.3 U/g protein) (p=0.017). Conclusions. Although primary hypolactasia normally appears before the age of 20 years, the decline in lactase activity may on rare occasions continue after that age. Genotyping of the C/T−13910 variant was found to be a reliable diagnostic approach in defining the lactase persistence/non-persistence status of the study subjects.

Intestinal defensin secretion in infancy is associated with the emergence of sensitization and atopic dermatitis

Intestinal flora and innate immunity, and their interactions impact adaptive immunity.

Intestinal cytokine mRNA expression in delayed-type cow's milk allergy.

Objectives: The aim of the study was to investigate the characteristics of intestinal immune activation (ie, a chemokine receptor and cytokine expression profile) in delayed-type cows milk allergy (CMA) appearing in the form of gastrointestinal symptoms. Patients and Methods: In all biopsy samples taken from the duodenum and/or the terminal ileum, 30 were studied for the expression of interferon-gamma, transforming growth factor-beta, chemokine receptor (CCR)-4, CCR-5, IL-2, IL-6, IL-10, IL-12p35, IL-12p40 and IL-18 specific mRNA by real-time quantitative reverse transcriptase-polymerase chain reaction in 26 children ages 3 to 15 years: 10 with untreated delayed-type CMA, 6 with celiac disease (CD) and 10 controls. Results: The children with delayed-type CMA showed lower IL-2 and IL-18 mRNA expression in the duodenum (both P = 0.055) and higher CCR-4 and IL-6 mRNA expression in the terminal ileum (P = 0.055, P = 0.016) compared with the controls. The children with CD exhibited slightly higher expression of interferon-gamma and CCR-4 mRNA (P = 0.054, P = 0.053) and lower expression of IL-18 mRNA (P = 0.004) in the duodenal samples compared with the controls. The mRNA expression levels of regulatory cytokines, transforming growth factor-beta and IL-10 remained similar in all 3 groups. Conclusions: The children with delayed-type gastrointestinal CMA showed a unique pattern of local intestinal hypersensitivity with Th2 response-related characteristics, a profile differing clearly from the children with CD.

No difference in symptoms during challenges with homogenized and unhomogenized cow's milk in subjects with subjective hypersensitivity to homogenized milk

It has been hypothesized that certain consumers tolerate untreated cows milk, but react to processed (i.e. homogenized and pasteurized) cows milk although they do not suffer from IgE-mediated cows milk allergy or lactose intolerance. The aim of the study was to compare the tolerance of unhomogenized and homogenized cows milk in lactose tolerant adults who had repeatedly experienced better tolerance of unhomogenized than homogenized milk. Forty-four subjects were challenged with homogenized and unhomogenized cows milk for five days in a randomized, double-blind, cross-over study. No differences in the symptoms during the challenges were found. Roughly half the subjects tolerated the homogenized milk better and the other half tolerated the unhomogenized milk better. The results of this study show no difference in the tolerance of homogenized and unhomogenized milk in adults with self-reported symptoms suggestive of hypersensitivity to homogenized milk.

Impaired tolerance of indigestible carbohydrates in adults with subjective milk intolerance

Background: Some Finns report a diminution of milk-related gastrointestinal symptoms when they travel or live abroad. Change in the overall diet may explain the diminution of symptoms. Objective: The aim was to determine whether these symptomatic subjects are actually sensitive to indigestible carbohydrates found in a typical Finnish diet. Design: Nineteen symptomatic subjects whose milk-related symptoms decreased abroad were interviewed. Symptoms and hydrogen excretion were measured after ingestion of rye bread and xylitol in six symptomatic and nine control subjects. In addition, gastrointestinal symptoms during 3 day interventions with rye and wheat bread were studied in five symptomatic subjects. Results: The symptomatic subjects experienced more symptoms than the controls after rye bread and xylitol ingestion (p=0.0003, p=0.042). Breath hydrogen excretion was similar in both groups. The symptomatic subjects experienced more symptoms during the rye bread than the wheat bread intervention (p=0.036). Conclusion: Some individuals reporting milk-related gastrointestinal symptoms may actually react to indigestible carbohydrates in the diet. Keywords: gastrointestinal symptoms; lactose malabsorption; rye bread; xylitol