Early-life gut microbiota associates with allergic rhinitis during 13-year follow-up in a Finnish probiotic intervention cohort.

Perinatal and early-life factors reported to affect risk of allergic diseases may be mediated by changes in the gut microbiota. Here, we explored the associations between the infant gut microbiota and allergic morbidity in childhood until 13 years of age in a subgroup of the FLORA probiotic intervention cohort. A mixture of four probiotic strains with galacto-oligosaccharides was administrated to the mothers from the 36th week of the pregnancy and later to their infants until 6 months of age. The infants were monitored for the manifestations of atopic eczema, food allergy, allergic rhinitis, and asthma by a pediatrician at 2 and 5 years of age; the allergic status was subsequently verified by a questionnaire at 10 and 13 years of age. The fecal microbiota at 3 months was profiled by 16S rRNA amplicon sequencing targeting the V3-V4 region, with and without adjusting for potentially important early-life factors. Overall, the positive diagnosis for allergic rhinitis between 2 and 13 years was associated with microbiota composition both in non-adjusted and adjusted models. This association was more pronounced in children born to one parent with confirmed atopic diseases compared to those who had two atopic parents and was characterized by a lower relative abundance of Bifidobacterium and Escherichia/Shigella spp. and a higher proportion of Bacteroides. While the probiotic and galacto-oligosaccharides intervention in the entire cohort was previously shown to reduce the prevalence of eczema to a certain extent, no associations were found between the 3-month gut microbiota and childhood eczema in the studied sub-cohort.IMPORTANCEAllergic diseases have increased in prevalence during the past decades globally. Although probiotics have been considered a promising strategy for preventing certain allergy related symptoms, studies connecting the infant gut microbiota and later life allergic morbidity in various populations remain limited. The present study supports an association between the infant microbiota and allergic morbidity after first years of life, which has been rarely examined.CLINICAL TRIALSRegistered at ClinicalTrials.gov (NCT00298337).

Early-life environment and the risk of eczema at 2 years-Meta-analyses of six Finnish birth cohorts.

BACKGROUND: Urban-related nature exposures are suggested to contribute to the rising prevalence of allergic diseases despite little supporting evidence. Our aim was to evaluate the impact of 12 land cover classes and two greenness indices around homes at birth on the development of doctor-diagnosed eczema by the age of 2 years, and the influence of birth season. METHODS: Data from 5085 children were obtained from six Finnish birth cohorts. Exposures were provided by the Coordination of Information on the Environment in three predefined grid sizes. Adjusted logistic regression was run in each cohort, and pooled effects across cohorts were estimated using fixed or random effect meta-analyses. RESULTS: In meta-analyses, neither greenness indices (NDVI or VCDI, 250 m × 250 m grid size) nor residential or industrial/commercial areas were associated with eczema by age of 2 years. Coniferous forest (adjusted odds ratio 1.19; 95% confidence interval 1.01-1.39 for the middle and 1.16; 0.98-1.28 for the highest vs. lowest tertile) and mixed forest (1.21; 1.02-1.42 middle vs. lowest tertile) were associated with elevated eczema risk. Higher coverage with agricultural areas tended to associate with elevated eczema risk (1.20; 0.98-1.48 vs. none). In contrast, transport infrastructure was inversely associated with eczema (0.77; 0.65-0.91 highest vs. lowest tertile). CONCLUSION: Greenness around the home during early childhood does not seem to protect from eczema. In contrast, nearby coniferous and mixed forests may increase eczema risk, as well as being born in spring close to forest or high-green areas.

Gut microbiota develop towards an adult profile in a sex-specific manner during puberty.

Accumulating evidence indicates that gut microbiota may regulate sex-hormone levels in the host, with effects on reproductive health. Very little is known about the development of intestinal microbiota during puberty in humans. To assess the connection between pubertal timing and fecal microbiota, and to assess how fecal microbiota develop during puberty in comparison with adult microbiota, we utilized a Finnish allergy-prevention-trial cohort (Flora). Data collected at 13-year follow-up were compared with adult data from a different Finnish cohort. Among the 13-year-old participants we collected questionnaire information, growth data from school-health-system records and fecal samples from 148 participants. Reference adult fecal samples were received from the Health and Early Life Microbiota (HELMi) cohort (n = 840). Fecal microbiota were analyzed using 16S rRNA gene amplicon sequencing; the data were correlated with pubertal timing and compared with data on adult microbiota. Probiotic intervention in the allergy-prevention-trial cohort was considered as a confounding factor only. The main outcome was composition of the microbiota in relation to pubertal timing (time to/from peak growth velocity) in both sexes separately, and similarity to adult microbiota. In girls, fecal microbiota became more adult-like with pubertal progression (p = 0.009). No such development was observed in boys (p = 0.9). Both sexes showed a trend towards increasing relative abundance of estrogen-metabolizing Clostridia and decreasing Bacteroidia with pubertal development, but this was statistically significant in girls only (p = 0.03). In girls, pubertal timing was associated positively with exposure to cephalosporins prior to the age of 10. Our data support the hypothesis that gut microbiota, particularly members of Ruminococcaceae, may affect pubertal timing, possibly via regulating host sex-hormone levels.Trial registration The registration number for the allergy-prevention-trial cohort: ClinicalTrials.gov, NCT00298337, registered 1 March 2006-Retrospectively registered, https://clinicaltrials.gov/show/NCT00298337 . The adult-comparison cohort (HELMi) is NCT03996304.

Dietary compliance in a randomized double-blind infant feeding trial during infancy aiming at prevention of type 1 diabetes.

The international Trial to Reduce IDDM in the Genetically at Risk (TRIGR) tested the hypothesis whether extensively hydrolyzed casein-based versus regular cow's milk-based infant formula reduces the risk of type 1 diabetes. We describe dietary compliance in the trial in terms of study formula intake, feeding of nonrecommended foods, and serum cow's milk antibody concentration reflecting intake of cow's milk protein among 2,159 eligible newborn infants with a biological first-degree relative affected by type 1 diabetes and with HLA-conferred susceptibility to type 1 diabetes. The participating infants were introduced to the study formula feeding at the median age of 15 days with a median duration of study formula use of 63 days. During the intervention, 80% of the infants received study formula. Of these, 57% received study formula for at least 2 months. On average, 45.5 l of study formula were used per infant. Only 13% of the population had received a nonrecommended food by the age of 6 months. The dietary compliance was similar in the intervention and control arm. The reported cow's milk consumption by the families matched very well with measured serum casein IgA and IgG antibody concentration. To conclude, good compliance was observed in this randomized infant feeding trial. Compliance varied between the regions and those infants who were breastfed for a longer period of time had a shorter exposure to the study formula. High dietary compliance in infant feeding trial is necessary to allow accurate interpretation of study results.

Effect of extensively hydrolyzed casein vs. conventional formula on the risk of asthma and allergies: The TRIGR randomized clinical trial.

BACKGROUND: The role of hydrolyzed infant formulas in the prevention of asthma and allergies remains inconsistent. We tested whether extensively hydrolyzed casein formula compared to conventional cow's milk-based formula prevented asthma, allergic rhinitis, or atopic eczema. METHODS: In the randomized double-blind Trial to Reduce IDDM in Genetically at Risk (TRIGR), comparing extensively hydrolyzed to standard cow's milk-based infant formula during the first 6-8 months of life, we assessed the effect of the intervention on the incidence of asthma, allergic rhinitis, and eczema when the children were 9- to 11-years old. The asthma, allergic rhinitis, and eczema occurrence was assessed using online standardized and validated ISAAC questionnaire. Of the 1106 children who participated in this Ancillary study, 560 had been randomized to the experimental (extensively hydrolyzed casein formula) and 546 to the control arm (cow's milk-based formula). RESULTS: The risk of persistent asthma, allergic rhinitis, or atopic eczema did not differ by treatment, the hazard ratios (95% CI) being 1.00 (0.66-1.52), 0.95 (0.66-1.38), and 0.89 (0.70-1.15), respectively, in the intention-to-treat analysis. Neither were there any differences in the per-protocol analysis. CONCLUSIONS: Extensively hydrolyzed casein formula did not protect from asthma, rhinitis, or eczema in this population carrying genetic risk for type 1 diabetes.

Allergic symptoms and sensitisation in adolescents with cows' milk allergy and atopic eczema in infancy.

BACKGROUND: The association between atopic sensitisation, atopic eczema (AE) and asthma is known, but distinct roles of allergies on long-term health are unestablished. OBJECTIVE: Evaluation of allergic symptoms and sensitisation in adolescents who in infancy had AE and verified cows' milk allergy (CMA) or AE and a negative CMA challenge, and controls. METHODS: Children with AE, with and without CMA, from a randomised controlled study in 1999-2001 examining the effect of probiotics on AE severity at older than 12 months of age, attended a follow-up visit at age 16 to 18, with age-matched controls. Data came from a questionnaire (ISAAC questionnaire), analysis of serum antigen-specific immunoglobulin Es (IgEs), and clinical evaluation. Group comparisons were carried out (χ2 tests and logistic regression). RESULTS: Fifty-two patients with AE and CMA (AE/CMA+ group), 52 with AE and suspicion of CMA (AE/CMA- group), and 57 controls attended a study visit. IgE-mediated sensitisation was significantly more prevalent in the AE/CMA+ group vs the controls, for horse, cat, dog, egg white and wheat (P < .024 for all). For birch, timothy and mugwort (P < .008 for all), sensitisation was more prevalent in both the AE/CMA+ group and the AE/CMA- group vs controls. On the basis of questionnaire data the AE/CMA + group reported a significantly higher lifetime prevalence of wheezing (64% vs 35% and 32%; P = .001), noninfectious rhinitis (85% vs 62% and 56%; P = .004), and hay fever (77% vs 52% and 33%; P < .001) vs the AE/CMA- group and the control group, respectively. CONCLUSION AND CLINICAL RELEVANCE: Patients with AE and CMA in infancy, as opposed to patients with AE only, or controls, report more allergic symptoms and exhibit more allergic sensitisation in adolescence. This indicates that CMA in infancy is an independent risk factor of allergic disease in adolescence.

Perinatal Probiotic Mixture and Development of Allergic Sensitization up to 13 Years of Age.

BACKGROUND: Probiotics have shown promising results in primary prevention of allergies in early years, but the long-term effects on allergic sensitization need more evaluation. OBJECTIVES: We conducted a randomized double-blind placebo-controlled study to determine whether the use of a mixture of pre- and probiotics perinatally affects the prevalence of immunoglobulin E (IgE) sensitization up to 13 years in high-risk children. METHODS: One thousand two hundred twenty-three pregnant women were randomized to receiving probiotics or placebo from 36 gestational weeks until delivery, and their infants received pre- and probiotics or placebo from birth until 6 months. At 2, 5, and 13 years, blood samples were taken to determine specific IgE levels against common foods, pollen, and animal antigens. RESULTS: The prevalence of IgE sensitization to any allergen was high and increased with age. No significant difference in the prevalence of IgE sensitization to any particular one of the tested allergens was found between the groups. At 2, 5, and 13 years these prevalence rates of IgE sensitization to any allergen were 31.1 and 34.1%, 50.1 and 45.6%, and 61.4 and 56.8% in the probiotic and placebo groups, respectively. At 13 years, IgE sensitization to cat/dog dander was more frequent in the probiotic group compared to the placebo group (40.2 vs. 31.0%, p = 0.03). CONCLUSIONS: In high-risk children, perinatal use of a mixture of probiotics did not affect the prevalence of sensitization to any one of the tested allergens, but it was associated with more frequent IgE sensitization to cat/dog dander at 13 years.

Perinatal probiotic intervention prevented allergic disease in a Caesarean-delivered subgroup at 13-year follow-up.

BACKGROUND: The long-term effects of probiotic intervention for primary prevention of allergic diseases are not well known. We previously reported less eczema until 10 years in our probiotic intervention trial. OBJECTIVE: To investigate the effect of early probiotic intervention on the prevalence of allergic diseases up to 13 years of age. METHODS: Pregnant women (n = 1223) carrying a child at a high risk of allergy (at least one parent with allergic disease) were randomized to receive a mixture of probiotics (Lactobacillus rhamnosusGG and LC705, Bifidobacterium breve Bb99 and Propionibacterium freudenreichii) or placebo in a double-blind manner from 36 weeks of gestation until birth. Their infants received the same product for the first six months (registration number NCT00298337). At 13-year follow-up, the participants were requested to return a questionnaire and to provide a blood sample. RESULTS: A questionnaire was returned by 642 participants (63.1% of intention-to-treat infants), and 459 provided a blood sample. In the whole cohort, there were no statistically significant differences in doctor-diagnosed allergic disease (55.2% and 59.0%, probiotic and placebo group, respectively) or allergic disease (47.9% and 51.6%) based on the ISAAC questionnaire data. Inhalant-specific IgE sensitization (>0.7 kU/L) was 59.3% in the probiotic group and 49.8% in the placebo group (P = 0.040). In a post hoc analysis made in Caesarean-delivered subgroup, allergy was reported in 41.5% of the probiotic group and 67.9% of the placebo group (P = 0.006), and eczema in 18.9% and 37.5%, respectively (P = 0.031). In the whole cohort, 8.5% of the probiotic group had suffered from wheezing attacks during the previous 12 months vs 14.7% in the placebo group (P = 0.013). There were no statistically significant differences discovered between the characteristics of the participating group and the dropout group. CONCLUSIONS: Probiotic intervention protected Caesarean-delivered subgroup from allergic disease and eczema, but not the total cohort.

Probiotic supplementation restores normal microbiota composition and function in antibiotic-treated and in caesarean-born infants.

BACKGROUND: Infants born by caesarean section or receiving antibiotics are at increased risk of developing metabolic, inflammatory and immunological diseases, potentially due to disruption of normal gut microbiota at a critical developmental time window. We investigated whether probiotic supplementation could ameliorate the effects of antibiotic use or caesarean birth on infant microbiota in a double blind, placebo-controlled randomized clinical trial. Mothers were given a multispecies probiotic, consisting of Bifidobacterium breve Bb99 (Bp99 2 × 108 cfu) Propionibacterium freundenreichii subsp. shermanii JS (2 × 109cfu), Lactobacillus rhamnosus Lc705 (5 × 109 cfu) and Lactobacillus rhamnosus GG (5 × 109 cfu) (N = 168 breastfed and 31 formula-fed), or placebo supplement (N = 201 breastfed and 22 formula-fed) during pregnancy, and the infants were given the same supplement. Faecal samples of the infants were collected at 3 months and analyzed using taxonomic, metagenomic and metaproteomic approaches. RESULTS: The probiotic supplement had a strong overall impact on the microbiota composition, but the effect depended on the infant's diet. Only breastfed infants showed the expected increase in bifidobacteria and reduction in Proteobacteria and Clostridia. In the placebo group, both birth mode and antibiotic use were significantly associated with altered microbiota composition and function, particularly reduced Bifidobacterium abundance. In the probiotic group, the effects of antibiotics and birth mode were either completely eliminated or reduced. CONCLUSIONS: The results indicate that it is possible to correct undesired changes in microbiota composition and function caused by antibiotic treatments or caesarean birth by supplementing infants with a probiotic mixture together with at least partial breastfeeding. TRIAL REGISTRATION: clinicaltrials.gov NCT00298337 . Registered March 2, 2006.

Fucosylated oligosaccharides in mother's milk alleviate the effects of caesarean birth on infant gut microbiota.

One of the most abundant components in human milk is formed by oligosaccharides, which are poorly digested by the infant. The oligosaccharide composition of breast milk varies between mothers, and is dependent on maternal secretor (FUT2) genotype. Secretor mothers produce milk containing α1-2 fucosylated human milk oligosaccharides, which are absent in the milk of non-secretor mothers. Several strains of bacteria in the infant gut have the capacity to utilise human milk oligosaccharides (HMOs). Here we investigate the differences in infant gut microbiota composition between secretor (N = 76) and non-secretor (N = 15) mothers, taking into account birth mode. In the vaginally born infants, maternal secretor status was not associated with microbiota composition. In the caesarean-born, however, many of the caesarean-associated microbiota patterns were more pronounced among the infants of non-secretor mothers compared to those of secretor mothers. Particularly bifidobacteria were strongly depleted and enterococci increased among the caesarean-born infants of non-secretor mothers. Furthermore, Akkermansia was increased in the section-born infants of secretor mothers, supporting the suggestion that this organism may degrade HMOs. The results indicate that maternal secretor status may be particularly influential in infants with compromised microbiota development, and that these infants could benefit from corrective supplementation.

Early fecal microbiota composition in children who later develop celiac disease and associated autoimmunity.

OBJECTIVES: Several studies have reported that the intestinal microbiota composition of celiac disease (CD) patients differs from healthy individuals. The possible role of gut microbiota in the pathogenesis of the disease is, however, not known. Here, we aimed to assess the possible differences in early fecal microbiota composition between children that later developed CD and healthy controls matched for age, sex and HLA risk genotype. MATERIALS AND METHODS: We used 16S rRNA gene sequencing to examine the fecal microbiota of 27 children with high genetic risk of developing CD. Nine of these children developed the disease by the age of 4 years. Stool samples were collected at the age of 9 and 12 months, before any of the children had developed CD. The fecal microbiota composition of children who later developed the disease was compared with the microbiota of the children who did not have CD or associated autoantibodies at the age of 4 years. Delivery mode, early nutrition, and use of antibiotics were taken into account in the analyses. RESULTS: No statistically significant differences in the fecal microbiota composition were found between children who later developed CD (n = 9) and the control children without disease or associated autoantibodies (n = 18). CONCLUSIONS: Based on our results, the fecal microbiota composition at the age of 9 and 12 months is not associated with the development of CD. Our results, however, do not exclude the possibility of duodenal microbiota changes or a later microbiota-related trigger for the disease.

Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial.

Importance: Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. Objective: To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. Design, Setting, and Participants: An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. Interventions: The participants received either a casein hydrolysate or a conventional adapted cow's milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. Main Outcomes and Measures: Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). Results: Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8% [95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). Conclusions and Relevance: Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes. Trial Registration: clinicaltrials.gov Identifier: NCT00179777.

Celiac Disease by the Age of 13 Years Is Not Associated With Probiotics Administration in Infancy.

Probiotics are theoretically promising in primary prevention of celiac disease (CD), but research evidence on the topic is scarce. We used the data and material of a clinical double-blind randomized placebo-controlled trial on primary allergy prevention (n = 1223) to investigate in an exploratory study whether administration of a mix of pro- and prebiotics during late pregnancy and first 6 months of life was associated with prevalence of CD during 13-year follow-up. Children who fulfilled diagnostic criteria for CD (n = 11) and subjects with a serum sample available for analyzing CD antibodies (n = 867) were included. CD or elevated tissue transglutaminase IgA antibodies were not associated with probiotics or placebo. Nor were there any associations with the mode of delivery, the duration of exclusive or total breast-feeding, or respiratory infections during the first 2 years of life. Allergic diseases or sensitization by the age of 2 or 5 years were not clearly associated with the development of CD.

Avoidance of Cow's Milk-Based Formula for At-Risk Infants Does Not Reduce Development of Celiac Disease: A Randomized Controlled Trial.

BACKGROUND & AIMS: Feeding during the first months of life might affect risk for celiac disease. Individuals with celiac disease or type 1 diabetes have been reported to have high titers of antibodies against cow's milk proteins. Avoidance of cow's milk-based formula for infants with genetic susceptibility for type 1 diabetes reduced the cumulative incidence of diabetes-associated autoantibodies. We performed a randomized controlled trial in the same population to study whether weaning to an extensively hydrolyzed formula reduced the risk of celiac disease autoimmunity or celiac disease. METHODS: We performed a double-blind controlled trial of 230 infants with HLA-defined predisposition to type 1 diabetes and at least 1 family member with type 1 diabetes. The infants were randomly assigned to groups fed a casein hydrolysate formula (n = 113) or a conventional formula (control, n = 117) whenever breast milk was not available during the first 6-8 months of life. Serum samples were collected over a median time period of 10 years and analyzed for antibodies to tissue transglutaminase (anti-TG2A) using a radiobinding assay, to endomysium using an immunofluorescence assay, and antibodies to a deamidated gliadine peptide using an immunofluorometry assay. Duodenal biopsies were collected if levels of anti-TG2A exceeded 20 relative units. Cow's milk antibodies were measured during the first 2 years of life. RESULTS: Of the 189 participants analyzed for anti-TG2A, 25 (13.2%) tested positive. Of the 230 study participants observed, 10 (4.3%) were diagnosed with celiac disease. We did not find any significant differences at the cumulative incidence of anti-TG2A positivity (hazard ratio, 1.14; 95% confidence interval, 0.51-2.54) or celiac disease (hazard ratio, 4.13; 95% confidence interval, 0.81-21.02) between the casein hydrolysate and cow's milk groups. Children who developed celiac disease had increased titers of cow's milk antibodies before the appearance of anti-TG2A or celiac disease. CONCLUSIONS: In a randomized controlled trial of 230 infants with genetic risk factors for celiac disease, we did not find evidence that weaning to a diet of extensively hydrolyzed formula compared with cow's milk-based formula would decrease the risk for celiac disease later in life. Increased titers of cow's milk antibody before anti-TG2A and celiac disease indicates that subjects with celiac disease might have increased intestinal permeability in early life. ClinicalTrials.gov Number: NCT00570102.

Intestinal Microbiota Signatures Associated With Histological Liver Steatosis in Pediatric-Onset Intestinal Failure.

BACKGROUND: Intestinal failure (IF)-associated liver disease (IFALD) is the major cause of mortality in IF. The link between intestinal microbiota and IFALD is unclear. METHODS: We compared intestinal microbiota of patients with IF (n = 23) with healthy controls (n = 58) using culture-independent phylogenetic microarray analysis. The microbiota was related to histological liver injury, fecal markers of intestinal inflammation, matrix metalloproteinase 9 and calprotectin, and disease characteristics. RESULTS: Overabundance of Lactobacilli, Proteobacteria, and Actinobacteria was observed in IF, whereas bacteria related to Clostridium clusters III, IV, and XIVa along with overall diversity and richness were reduced. Patients were segregated into 3 subgroups based on dominating bacteria: Clostridium cluster XIVa, Proteobacteria, and bacteria related to Lactobacillus plantarum. In addition to liver steatosis and fibrosis, Proteobacteria were associated with prolonged current parenteral nutrition (PN) as well as liver and intestinal inflammation. Lactobacilli were related to advanced steatosis and fibrosis mostly after weaning off PN without associated inflammation. In multivariate permutational analysis of variance, liver steatosis, bowel length, PN calories, and antibiotic treatment best explained the microbiota variation among patients with IF. CONCLUSIONS: Intestinal microbiota composition was associated with liver steatosis in IF and better predicted steatosis than duration of PN or length of the remaining intestine. Our results may be explained by a model in which steatosis is initiated during PN in response to proinflammatory lipopolysaccharides produced by Proteobacteria and progresses after weaning off PN, as the L plantarum group Lactobacilli becomes dominant and affects lipid metabolism by altering bile acid signaling.

FUT2-dependent breast milk oligosaccharides and allergy at 2 and 5 years of age in infants with high hereditary allergy risk.

PURPOSE: Manifestation of allergic disease depends on genetic predisposition, diet and commensal microbiota. Genetic polymorphism of mothers determines their breast milk glycan composition. One major determinant is the fucosyltransferase 2 (FUT2, secretor gene) that was shown to be linked to commensal microbiota establishment. We studied whether FUT2-dependent breast milk oligosaccharides are associated with allergic disease in breast-fed infants later in life. METHODS: We analyzed FUT2-dependent oligosaccharides in breast milk samples of mothers (n = 266) from the placebo group of a randomized placebo-controlled trial of prebiotics and probiotics as preventive against allergic disease in infants with high allergy risk (trial registry number: NCT00298337). Using logistic regression models, we studied associations between FUT2-dependent breast milk oligosaccharides and incidence of allergic disease at 2 and 5 years of age. RESULTS: At 2 years, but not at 5 years of age, we observed a presumed lower incidence (p < 0.1) for IgE-associated eczema manifestation in C-section-born infants who were fed breast milk containing FUT2-dependent oligosaccharides. By logistic regression, we observed a similar relation (p < 0.1) between presence of FUT2-dependent breast milk oligosaccharides and IgE-associated disease and IgE-associated eczema in C-section-born infants only. When testing with the levels of breast milk oligosaccharide 2'-fucosyllactose as proxy for FUT2 activity, we observed significant (p < 0.05) associations in the C-section-born infants with 'any allergic disease,' IgE-associated disease, eczema and IgE-associated eczema. CONCLUSION: The data indicate that infants born by C-section and having a high hereditary risk for allergies might have a lower risk to manifest IgE-associated eczema at 2 years, but not 5 years of age, when fed breast milk with FUT2-dependent milk oligosaccharides. Further studies with larger cohorts and especially randomized controlled intervention trials are required to build on these preliminary observations.

Regional differences in milk and complementary feeding patterns in infants participating in an international nutritional type 1 diabetes prevention trial.

Differences in breastfeeding, other milk feeding and complementary feeding patterns were evaluated in infants at increased genetic risk with and without maternal type 1 diabetes (T1D). The Trial to Reduce IDDM in the Genetically at Risk is an international nutritional primary prevention double-blinded randomized trial to test whether weaning to extensively hydrolyzed vs. intact cow's milk protein formula will decrease the development of T1D-associated autoantibodies and T1D. Infant diet was prospectively assessed at two visits and seven telephone interviews between birth and 8 months. Countries were grouped into seven regions: Australia, Canada, Northern Europe, Southern Europe, Central Europe I, Central Europe II and the United States. Newborn infants with a first-degree relative with T1D and increased human leukocyte antigen-conferred susceptibility to T1D were recruited. A lower proportion of infants born to mothers with than without T1D were breastfed until 6 months of age in all regions (range, 51% to 60% vs. 70% to 80%). Complementary feeding patterns differed more by region than by maternal T1D. In Northern Europe, a higher proportion of infants consumed vegetables and fruits daily compared with other regions. Consumption of meat was more frequent in all European regions, whereas cereal consumption was most frequent in Southern Europe, Canada and the United States. Maternal T1D status was associated with breastfeeding and other milk feeding patterns similarly across regions but was unrelated to the introduction of complementary foods. Infant feeding patterns differed significantly among regions and were largely inconsistent with current recommended guidelines.