Late preterm birth has direct and indirect effects on infant gut microbiota development during the first six months of life.

AIM: Preterm infants display aberrant gut microbial colonisation. We investigated whether the differences in gut microbiota between late preterm and full-term infants results from prematurity or external exposures. METHODS: This study comprised 43 late preterm infants (340/7 -366/7 ) and 75 full-term infants based on faecal samples collected following birth and at two to four weeks and six months of age. We assessed clinically relevant bacteria using quantitative polymerase chain reaction. Logistic regression analyses were performed to determine whether the observed differences in gut microbiota were attributable to prematurity or perinatal exposure. RESULTS: The prevalence of bifidobacteria differed in the intestinal microbiota of the full-term and late preterm neonates. Differences in the presence of specific species were detected at the age of six months, although the microbiota alterations were most prominent following delivery. As well as prematurity, the mode of birth, intrapartum and neonatal antibiotic exposure, and the duration of breastfeeding had an additional impact on gut microbiota development. CONCLUSION: The gut microbiota composition was significantly different between late preterm and full-term infants at least six months after birth. Antibiotic exposure was common in late preterm infants and modulated gut colonisation, but preterm birth also affected gut microbiota development independently.

Severity of atopic disease inversely correlates with intestinal microbiota diversity and butyrate-producing bacteria.

The reports on atopic diseases and microbiota in early childhood remain contradictory, and both decreased and increased microbiota diversity have been associated with atopic eczema. In this study, the intestinal microbiota signatures associated with the severity of eczema in 6-month-old infants were characterized. Further, the changes in intestinal microbiota composition related to the improvement of this disease 3 months later were assessed. The severity of eczema correlated inversely with microbiota diversity (r = -0.54, P = 0.002) and with the abundance of butyrate-producing bacteria (r = -0.52, P = 0.005). During the 3-month follow-up, microbiota diversity increased (P < 0.001) and scoring atopic dermatitis values decreased (P < 0.001) in all infants. This decrease coincided with the increase in bacteria related to butyrate-producing Coprococcus eutactus (r = -0.59, P = 0.02). In conclusion, the high diversity of microbiota and high abundance of butyrate-producing bacteria were associated with milder eczema, thus suggesting they have a role in alleviating symptoms of atopic eczema.

Role of probiotics in reducing the risk of gestational diabetes.

Overweight and obesity currently constitute a major threat to human well-being. Almost half of the female population are currently overweight. Pregnant overweight women are at risk of gestational diabetes affecting the health of the mother and the child, in both the short and long term. Notwithstanding the extensive scientific interest centred on the problem, research efforts have thus far been unable to devise preventive strategies. Recent scientific advances point to a gut microbiota dysbiosis, with ensuing low-grade inflammation as a contributing element, in obesity and its comorbidities. Such findings would suggest a role for specific probiotics in the search for preventive and therapeutic adjunct applications in gestational diabetes. The aim of the present paper was to critically review recent demonstrations of the role of intestinal microbes in immune and metabolic regulation, which could be exploited in nutritional management of pregnant women by probiotic bacteria. By modulating specific target functions, probiotic dietary intervention may exert clinical effects beyond the nutritional impact of food. As this approach in pregnancy is new, an overview of the role of gut microbiota in shaping host metabolism, together with the definition of probiotics are presented, and finally, specific targets and potential mechanisms for probiotics in pregnancy are discussed. Pregnancy appears to be the most critical stage for interventions aiming to reduce the risk of non-communicable disease in future generations, beyond the immediate dangers attributable to the health of the mother, labour and the neonate. Specific probiotic interventions during pregnancy provide an opportunity, therefore, to promote the health not only of the mother but also of the child.

Diet and blood lipids in 1-4 year-old children.

BACKGROUND AND AIM: Early nutrition may programme blood lipid levels and thereby later cardiovascular health of children. The objective here was to evaluate the effects of maternal dietary counselling during pregnancy and breastfeeding on dietary intakes and blood lipid values in 1-4 year-old children. Further, the nutritional determinants of children's lipid profiles were assessed. METHODS AND RESULTS: Mothers were randomised into dietary counselling or control groups at the first trimester of pregnancy. Their children were followed up clinically at 1, 2 and 4 years of age, by three-day food records and analyses of total cholesterol, HDL cholesterol and apolipoproteins A-I and B as well as lipoprotein (a). In general, the mean intake of saturated fatty acids as a proportion of total energy intake (E%) was higher than the recommended, while the mean intake of polyunsaturated fatty acids was low in children's diet. Over the first years, girls had higher concentration of non-HDL cholesterol than boys; 2.64 mmol/l (95% CI 2.54-2.74) vs. 2.49 (2.38-2.60); p = 0.038. Maternal dietary counselling was not reflected in the children's lipid values. Children's monounsaturated fatty acid intake (E%) correlated with apoA-I (p = 0.048) and, furthermore, there was a negative correlation between polyunsaturated fatty acid intake (E%) and apoB (p = 0.046). CONCLUSION: Children's dietary fatty acid intake, but not maternal dietary counselling was shown to be related to blood apolipoproteins in children.

Reshaping the gut microbiota at an early age: functional impact on obesity risk?

Overweight and obesity can currently be considered a major threat to human health and well-being. Recent scientific advances point to an aberrant compositional development of the gut microbiota and low-grade inflammation as contributing factors, in conjunction with excessive energy intake. A high-fat/energy diet alters the gut microbiota composition, which reciprocally engenders excessive energy harvesting and storage. Further, microbial imbalance increases gut permeability, leading to metabolic endotoxemia, inflammation and insulin resistance. Local intestinal immunologic homeostasis is achieved by tolerogenic immune responses to microbial antigens. In the context of amelioration of insulin sensitivity and decreased adiposity, the potential of gut microbiota modulation with specific probiotics and prebiotics lies in the normalization of aberrant microbiota, improved gut barrier function and creation of an anti-inflammatory milieu. This would suggest a role for probiotic/prebiotic interventions in the search for preventive and therapeutic applications in weight management.

Impact of intrauterine and post-natal nutritional determinants on blood pressure at 4 years of age.

BACKGROUND: To prospectively study how the early nutritional environment can programme blood pressure in a well-nourished population of children. METHODS: By means of multivariate modelling, we assessed whether gestational and post-natal dietary intakes and growth influence childhood blood pressure programming in a cohort of 109 healthy mother-child pairs. They had been followed from early pregnancy until the children reached 4 years of age. Dietary intakes were evaluated using 3-day food diaries. Blood pressure levels in the children were measured using an automated oscillometric DINAMAP ProCare 100 (Criticon, Tampa, FL, USA) at the age of 4 years. RESULTS: In the final multivariate model, the predictor variables of childhood systolic blood pressure were maternal dietary carbohydrate and fat intake during pregnancy, as well as childhood weight and dietary fat intake at 4 years of age. Systolic blood pressure levels in the children were found to be positively associated with the maternal carbohydrate intake (P = 0.003), whereas blood pressure levels were lowest in children exposed to the middle tertile of maternal dietary fat intake during pregnancy (P = 0.003) and whose own dietary fat intake was in the middle tertile at the age of 4 years (P = 0.013). The model also showed that heavier children have a higher systolic blood pressure (P < 0.001). None of the maternal clinical characteristics fulfilled the criterion to be included in the model. The only determinant underlying childhood diastolic blood pressure was childhood weight at 4 years of age (r = 0.289, P = 0.026). CONCLUSIONS: Interventions focusing on cardiovascular health in young women during pregnancy and their children should be considered to reduce cardiovascular diseases risk factors in these children.

Interaction of orally administered Lactobacillus rhamnosus GG with skin and gut microbiota and humoral immunity in infants with atopic dermatitis.

BACKGROUND: The intestinal mucosa functions as a defence barrier against gut intraluminar antigens. The maturational events in the gut parallel its step-wise colonization. Atopic dermatitis (AD) is associated with aberrant barrier functions of the skin epithelium and, in a subgroup of patients, of the gut mucosa. OBJECTIVE: To investigate the interaction of Lactobacillus rhamnosus GG (LGG) with skin and gut microbiota and humoral immunity in infants with AD. METHODS: Thirty-nine infants with AD were randomized for a 3-month period in a double-blind design to receive extensively hydrolysed casein formula supplemented with (n=19) or without (n=20) LGG (ATCC 53103) 5.0 × 107 CFU/g to achieve a daily intake of 3.4 × 109 CFU. Sampling (blood and fecal samples, cotton swab from the skin) was carried out at entry, 1 and 3 months thereafter. Ig-secreting cells were determined by enzyme-linked immunospot and the proportions of CD19(+)CD27(+) B cells among peripheral blood leucocytes by flow cytometry. The major groups of gut and skin bacteria were characterized using PCR. RESULTS: The proportions of IgA- and IgM-secreting cells decreased significantly in the treated group; the baseline-adjusted ratios for treated vs. untreated at 1 month were 0.59 (95%CI 0.36-0.99, P=0.044) for IgA- and 0.53 (95%CI 0.29-0.96, P=0.036) for IgM-secreting cells. The proportions of CD19(+)CD27(+) B cells increased in the probiotic-treated infants but not in the untreated. There were no significant differences in bifidobacterial species composition of the gut between the study groups. On the skin, the bacterial counts of Bifidobacterium genus vs. Clostridium coccoides in the treated and untreated infants were similar. CONCLUSION AND CLINICAL RELEVANCE: Specific probiotics may enhance gut barrier function and aid in the development of immune responses. Thus, specific probiotics may afford protection against offending macromolecules in the gut and provide control for future infections by accelerated immunological maturation (ClinicalTrials.gov ID NCT01148667).

The impact of perinatal probiotic intervention on the development of overweight and obesity: follow-up study from birth to 10 years.

BACKGROUND: The achievements in combating the increasing trend of overweight and obesity have thus far been inadequate. The recently discovered instrumental role of the gut microbiota in host metabolism may offer a novel target in the prevention and management of obesity. OBJECTIVE: To evaluate the impact of perinatal probiotic intervention on childhood growth patterns and the development of overweight during a 10-year follow-up. PATIENTS AND METHODS: Altogether 159 women were randomized and double-blinded to receive probiotics (1 × 10(10) colony-forming units of Lactobacillus rhamnosus GG, ATCC 53103) or placebo 4 weeks before expected delivery; the intervention extending for 6 months postnatally. Anthropometric measurements of the children were taken at the ages of 3, 6, 12 and 24 months and at 4, 7 and 10 years in 113 (72%) children. RESULTS: The excessive weight gain was detected to be two-parted; the initial phase of excessive weight gain initiating during fetal period and continuing until 24-48 months of age and a second phase of excessive weight gain starting after the age of 24-48 months. The perinatal probiotic intervention appeared to moderate the initial phase of excessive weight gain, especially among children who later became overweight, but not the second phase of excessive weight gain, the impact being most pronounced at the age of 4 years (P=0.063, analysis of variance for repeated measures). The effect of intervention was also shown as a tendency to reduce the birth-weight-adjusted mean body mass index at the age of 4 years (P=0.080, analysis of covariance). CONCLUSIONS: Early gut microbiota modulation with probiotics may modify the growth pattern of the child by restraining excessive weight gain during the first years of life. This novel observation calls for further epidemiological and clinical trials, with precise data on early growth patterns and on confounding factors influencing weight development.

Incidence of necrotizing enterocolitis in very-low-birth-weight infants related to the use of Lactobacillus GG.

BACKGROUND: One of the five level III neonatal intensive care units (NICU) in Finland has used prophylactic Lactobacillus GG (LGG) for very-low-birth-weight (VLBW) infants since 1997. AIM: To examine retrospectively the incidence of necrotizing enterocolitis (NEC) in all five university hospital NICUs in Finland in relation to the use of LGG during the years each unit has belonged to the Vermont Oxford Network (VON). METHODS: The incidence of NEC was analysed from the national database and from the VON databases separately in all five level III NICUs and additionally in three groups according to the probiotic practice in the hospitals: prophylactic LGG group, probiotics 'on demand' group and no probiotics group. RESULTS: The incidence of NEC was 4.6% vs. 3.3% vs. 1.8% in the prophylactic LGG group, the no probiotics group and the probiotics 'on demand' group [corrected] respectively; p = 0.0090, chi-square. LGG had no influence on the clinical course of NEC. CONCLUSIONS: The results of this retrospective report failed to show that LGG prophylaxis protects VLBW infants from the occurrence of NEC, in contrast to previously published results. Our results call for more research regarding effective ways to administer probiotics, including data on appropriate bacteria, strain, dose and timing of administration to achieve clinically robust effects.

Dietary and clinical impacts of nausea and vomiting during pregnancy.

BACKGROUND: Nutrition during pregnancy is important for the health of both mother and infant. Nausea and vomiting in pregnancy (NVP) may alter food intake but the dietary and clinical consequences of NVP are poorly understood. The present study aimed to identify the differences in dietary intakes and clinical characteristics of women with NVP compared with those without. METHODS: Women with (n = 134) or without (n = 53) NVP were studied in each trimester of pregnancy. The babies were studied at birth, and at 1 and 6 months. The presence of nausea and vomiting was established by interviews using standard questions. Daily intakes of foods and nutrients were assessed from 3-day food diaries. Weight gain during pregnancy and weights and lengths of the infants at birth and at 1 and 6 months of age were recorded. RESULTS: In the first trimester, intake of meat products and thus protein in women with NVP was lower both quantitatively (P = 0.007) and as a proportion of energy (16.4E% [interquartile range (IQR) 14.9-18.4]) compared to non-NVP [18.3E% (IQR 16.3-19.8), P = 0.003]. The proportional intakes of carbohydrates were higher in NVP subjects [50.1E% (IQR 46.7-53.6)] than in non-NVP [46.8E% (IQR 43.6-51.9), P = 0.008]. Dietary and total intakes of vitamin B(12), total intake of magnesium and dietary intake of zinc were lower in women with NVP. Changes in diet remained throughout pregnancy. Women with NVP had shorter pregnancies [39.9 (95% CI 39.6-40.1)] compared with those without [40.4 (95% CI 40.1-40.8) weeks, P = 0.018], but neither pregnancy weight gain nor infants' weight and length differed. CONCLUSIONS: Nausea and vomiting in pregnancy modified dietary intake and has potential clinical impacts as suggested by the altered pregnancy duration. In view of the programming effect of early nutrition, these alterations may carry long-term health consequences.

Plant stanol ester spreads as components of a balanced diet for pregnant and breast-feeding women: evaluation of clinical safety.

Clinical safety of consuming plant stanol ester spreads during pregnancy and lactation, the impact on maternal and infant serum and breast-milk cholesterol and the ratios (micromol/mmol of cholesterol) of synthesis and absorption markers were evaluated. Pregnant women (n 21) were randomised to control and dietary intervention groups, the intervention including advice to follow a balanced diet and to consume spreads enriched with plant stanol esters. Participants were followed during and after pregnancy and their infants up to 1 year of age. A mean 1.1 (sd 0.4) g consumption of plant stanols during pregnancy and 1.4 (sd 0.9) g 1 month post-partum increased sitostanol and the markers for cholesterol synthesis, lathosterol, lathosterol/campesterol and lathosterol/sitosterol, and reduced a marker for cholesterol absorption, campesterol, in maternal serum. In breast milk, desmosterol was lower in the intervention group, while no differences were detected between the groups in infants' serum. Plant stanol ester spread consumption had no impact on the length of gestation, infants' growth or serum beta-carotene concentration at 1 and 6 months of age, but the cholesterol-adjusted serum beta-carotene concentration was lowered at 1 month in the intervention group. Plant stanol ester spread consumption appeared safe in the clinical setting, except for potential lowering of infants' serum beta-carotene concentration, and was reflected in the markers of cholesterol synthesis and absorption in mothers' serum, encouraging further studies in larger settings.

Bifidobacterium and Lactobacillus DNA in the human placenta.

AIMS: Bifidobacteria and lactobacilli are part of the human normal intestinal microbiota and may possibly be transferred to the placenta. It was hypothesized that intestinal bacteria or their components are present in the placenta and that the foetus may be exposed to them. We investigated the presence of bifidobacteria and lactobacilli and their DNA in the human placenta. METHODS AND RESULTS: We studied 34 human placentae (25 vaginal and nine caesarean deliveries) for the presence Bifidobacterium spp. and Lactobacillus rhamnosus. Cultivation was used for the detection of viable cells and genus and species-specific PCR for the detection of DNA. No bifidobacteria or lactobacilli were found by cultivation. Bifidobacterial DNA was detected in 33 and L. rhamnosus DNA in 31 placenta samples. CONCLUSIONS: DNA from intestinal bacteria was found in most placenta samples. The results suggest that horizontal transfer of bacterial DNA from mother to foetus may occur via placenta. SIGNIFICANCE AND IMPACT OF THE STUDY: Bacterial DNA contains unmethylated CpG oligodeoxynucleotide motifs which induce immune effects. Specific CpG motifs activate Toll-like receptor 9 and subsequently trigger Th-1-type immune responses. Although the newborn infant is considered immunologically immature, exposure by bacterial DNA may programme the infant's immune development during foetal life earlier than previously considered.

Impact of maternal atopy and probiotic supplementation during pregnancy on infant sensitization: a double-blind placebo-controlled study.

BACKGROUND: The effects of breastfeeding and probiotics on infant sensitization still remain discrepant. OBJECTIVE: To explore probable explanatory factors in infant sensitization and the protective effect of probiotics. METHODS: Altogether 171 mother-infant pairs from an ongoing placebo-controlled double-blind study with nutrition modulation by dietary counselling and probiotic supplementation were studied. Skin prick testing was done in infants at 6 and 12 months and in mothers at third trimester of pregnancy. The breast milk concentrations of cytokines TGF-beta2, soluble CD14, IFN-gamma, TNF-alpha, IL-10, IL-6, IL-4 and IL-2 were measured. RESULTS: The risk of sensitization increased in infants with allergic mothers breastfeeding over 6 months [odds ratio (OR=4.83, P=0.005)], or exclusively breastfeeding over 2.5 months (OR=3.4, P=0.018). Probiotic supplementation had a protective effect against sensitization in infants with a high hereditary risk due to maternal sensitization (OR=0.3, P=0.023). The concentration of TGF-beta2 tended to be higher in the colostrum of the mothers in the probiotic group as compared with those on placebo (probiotic/placebo ratio=1.50, P=0.073). A similar result was obtained in the subgroup of allergic mothers (probiotic/placebo ratio=1.56, P=0.094). CONCLUSION: Infants of atopic mothers, specifically when breastfed exclusively over 2.5 months or totally over 6 months, had a higher risk of sensitization at the age of 12 months. This risk could be reduced by the use of probiotics during pregnancy and lactation, partly by resulting in a beneficial composition of the breast milk.

Maternal breast-milk and intestinal bifidobacteria guide the compositional development of the Bifidobacterium microbiota in infants at risk of allergic disease.

BACKGROUND: The sources and the impact of maternal bacteria on the initial inoculum of the intestinal microflora of newborn infants remain elusive. OBJECTIVE: To assess the association between maternal breast-milk and fecal bifidobacteria and infants' fecal bifidobacteria. METHODS: Sixty-one mother-infant pairs were included, special emphasis being placed on the maternal allergic status. Bifidobacteria were analysed by a direct PCR method in fecal samples from mothers at 30-35 weeks of gestation and from infants at 1 month of age and from breast-milk samples 1 month post-partum. RESULTS: Fecal Bifidobacterium adolescentis and Bifidobacterium bifidum colonization frequencies and counts among mother-infant pairs correlated significantly (P=0.005 and 0.02 for frequencies, respectively, and P=0.002 and 0.01 for counts, respectively). Only infants of allergic, atopic mothers were colonized with B. adolescentis. Each of the breast-milk samples contained bifidobacteria [median 1.4 x 10(3) bacterial cells/mL; interquartile range (IQR) 48.7-3.8 x 10(3)]. Bifidobacterium longum was the most frequently detected species in breast-milk. Allergic mothers had significantly lower amounts of bifidobacteria in breast-milk compared with non-allergic mothers [median 1.3 x 10(3) bacterial cells/mL (IQR 22.4-3.0 x 10(3)) vs. 5.6 x 10(3) bacterial cells/mL (1.8 x 10(3)-1.8 x 10(4)), respectively, (P=0.004)], and their infants had concurrently lower counts of bifidobacteria in feces [3.9 x 10(8) bacterial cells/g (IQR 6.5 x 10(6)-1.5 x 10(9)) in infants of allergic mothers, vs. 2.5 x 10(9) bacterial cells/g (6.5 x 10(8)-3.2 x 10(10)) in infants of non-allergic mothers, P=0.013]. CONCLUSIONS: Breast-milk contains significant numbers of bifidobacteria and the maternal allergic status further deranges the counts of bifidobacteria in breast-milk. Maternal fecal and breast-milk bifidobacterial counts impacted on the infants' fecal Bifidobacterium levels. Breast-milk bacteria should thus be considered an important source of bacteria in the establishment of infantile intestinal microbiota.

Impact of national fortification of fluid milks and margarines with vitamin D on dietary intake and serum 25-hydroxyvitamin D concentration in 4-year-old children.

OBJECTIVE: To assess the impact of national fortification of fluid milks and margarines with vitamin D on dietary intake and on serum 25-hydroxyvitamin D concentration in Finnish 4-year-old children. DESIGN, SUBJECTS AND METHODS: Two cohorts of children were studied during wintertime, one before (n=82) in 2001-2002 and the other after (n=36) the initiation of fortification in 2003-2004. Dietary intake was estimated by 4-day food records and serum 25-hydroxyvitamin D concentration was analyzed by radioimmunoassay. RESULTS: The mean intake of vitamin D was higher the after initiation of fortification (mean (95% confidence interval (CI)); 4.5 (3.8-5.1) microg) than before it (2.1 (95% CI 1.8-2.3) microg; P<0.001), although there were no differences in consumption of the main food sources of vitamin D between the two cohorts. The difference between the cohorts was also evident when the intake of vitamin D was adjusted for energy intake (0.78 (95% CI 0.70-0.90) and 0.37 (95% CI 0.32-0.42) microg/MJ after and before fortification, respectively, P<0.001). After fortification, the mean intake approached that recommended, but was achieved by only 30.6% of the children. Equally, the serum 25-hydroxyvitamin D concentration was higher after fortification (64.9 (95% CI 59.7-70.1) nmol/l) compared to prior it (54.7 (95% CI 51.0-58.4) nmol/l; P=0.002). CONCLUSIONS: The results indicate that the national fortification of fluid milks and margarines with vitamin D safely improved the vitamin D status of children. This approach, in view of the novel health effects beyond bone metabolism, encourages fortification of new food sources with vitamin D or use of vitamin D supplements particularly during wintertime.

Human milk oligosaccharide categories define the microbiota composition in human colostrum.

Human milk oligosaccharides (HMOs) are structurally diverse unconjugated glycans with a composition unique to each lactating mother. While HMOs have been shown to have an impact on the development of infant gut microbiota, it is not well known if HMOs also already affect milk microbial composition. To address this question, we analysed eleven colostrum samples for HMO content by high-pressure liquid chromatography and microbiota composition by quantitative PCR. Higher total HMO concentration was associated with higher counts of Bifidobacterium spp. (ρ=0.63, P=0.036). A distinctive effect was seen when comparing different HMO groups: positive correlations were observed between sialylated HMOs and Bifidobacterium breve (ρ=0.84, P=0.001), and non-fucosylated/non-sialylated HMOs and Bifidobacterium longum group (ρ=0.65, P=0.030). In addition to associations between HMOs and bifidobacteria, positive correlations were observed between fucosylated HMOs and Akkermansia muciniphila (ρ=0.70, P=0.017), and between fucosylated/sialylated HMOs and Staphylococcus aureus (ρ=0.75, P=0.007). Our results suggest that the characterised HMOs have an effect on specific microbial groups in human milk. Both oligosaccharides and microbes provide a concise inoculum for the compositional development of the infant gut microbiota.

Vitamin C in breast milk may reduce the risk of atopy in the infant.

OBJECTIVE: To assess the effects of maternal dietary and supplement intake of vitamins C and E on breast milk antioxidant composition (vitamin C, alpha-tocopherol and beta-carotene) and their protective potential against the development of atopy in the infant. DESIGN, SUBJECTS AND METHODS: Mothers with atopic disease were recruited at the end of gestation and maternal sensitization was assessed by skin-prick testing. The 4-day food records of the mothers and breast milk samples were collected at the infants' age of 1 month. Infants' atopy was defined by the presence of atopic dermatitis during the first year of life and a positive skin-prick test reaction at 12 months of age (n=34). RESULTS: Maternal intake of vitamin C in diet but not as supplement was shown to determine the concentration of vitamin C in breast milk. A higher concentration of vitamin C in breast milk was associated with a reduced risk of atopy in the infant (OR=0.30; 95% CI 0.09-0.94; P=0.038), whereas alpha-tocopherol had no consistent relationship with atopy. The group at risk of suboptimal vitamin C supply from breast milk was identified as infants whose mothers suffer from food hypersensitivity. CONCLUSION: A maternal diet rich in natural sources of vitamin C during breastfeeding could reduce the risk of atopy in high-risk infants.

The impact of early gut microbiota modulation on the risk of child disease: alert to accuracy in probiotic studies.

The composition of the gut microbiota, and thus also the modification of the gut microbiota by specific probiotics or prebiotics early in life, may have an impact on the risk of disease in the child. Above the impact on gut microecology, probiotic effects have been attributed to restoration to normal of increased intestinal permeability, improvement of the intestine's immunological barrier functions, alleviation of the intestinal inflammatory response, and reduced generation of proinflammatory cytokines characteristic of local and systemic allergic inflammation. Recent demonstrations from experimental and clinical studies suggest that the gut microbiota is also involved in the control of body weight and energy metabolism, affecting the two main causes of obesity: energy acquisition and storage, and contributing to insulin resistance and the inflammatory state characterising obesity. Current research focuses both on characterising specific probiotic strains and on how the food matrix and the dietary content interacts with the most efficient probiotic strains. It is important to characterise each probiotic to species and strain level and to select strains with documented properties, the probiotic potential being strain-specific. As any proof of causality requires clinical intervention studies in humans in different populations, rigorous and detailed documentation will enhance reproducibility and circumvent confusion.

Probiotics in human disease.

Western civilization is facing a progressive increase in immune-mediated, gut-related health problems, such as allergies and autoimmune and inflammatory diseases, and genetic factors are an unlikely explanation for these rapid increases in disease incidence. Two environmental factors that relate to the modern lifestyle in Western societies are hygiene and nutrition. There has been a decline in the incidence of microbial stimulation by infectious diseases as a result of improved hygiene, vaccination, and antimicrobial medication. In the past, methods of food preservation involved either the natural fermentation or drying of foods; thus, the human diet once contained several thousand times more bacteria than it does today. The development of probiotic, functional foods aims to "kill two birds with one stone," which is accomplished by providing a microbial stimulus to the host immune system by means of beneficial live microorganism cultures that are characteristic of the healthy, human gut microflora, ie, probiotics. Probiotic bacteria were shown to reinforce the different lines of gut defense, which are immune exclusion, immune elimination, and immune regulation. They were also shown to stimulate nonspecific host resistance to microbial pathogens, thereby aiding in pathogen eradication. Consequently, the best documented clinical application of probiotics is in the treatment of acute diarrhea. In humans, documented effects were reported for the alleviation of intestinal inflammation, normalization of gut mucosal dysfunction, and down-regulation of hypersensitivity reactions. These data show that probiotics promote endogenous host defense mechanisms. Thus, modification of gut microflora by probiotic therapy may offer a therapeutic potential in clinical conditions associated with gut-barrier dysfunction and inflammatory response.

Quality assurance criteria for probiotic bacteria.

Acid and bile stability and intestinal mucosal adhesion properties are among the criteria used to select probiotic microbes. The quality control of probiotic cultures in foods traditionally has relied solely on tests to ensure that an adequate number of viable bacteria are present in the products throughout their shelf lives. Viability is an important factor, but not the only criterion for quality assurance. To be effective, probiotic strains must retain the functional health characteristics for which they were originally selected. Such characteristics include the ability to survive transit through the stomach and small intestine and to colonize the human gastrointestinal tract. In vitro test protocols can be readily adopted to examine the maintenance of a strain's ability to tolerate acidic conditions, survive and grow in the presence of bile, and metabolize selective substrates. Molecular techniques are also available to examine strain stability. Adhesion characterization may be an important quality-control method for assessing gut barrier effects. Adhesion has been related to shortening the duration of diarrhea, immunogenic effects, competitive exclusion, and other health effects. Adhesion properties should be carefully monitored, including adhesion to intestinal cells (eg, Caco-2) and human intestinal mucus. This article outlines the types of in vitro testing that can be used to ensure quality control of functional probiotic strains.