Thomas R. Abrahamsson

Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by Caesarean section

Objective The early intestinal microbiota exerts important stimuli for immune development, and a reduced microbial exposure as well as caesarean section (CS) has been associated with the development of allergic disease. Here we address how microbiota development in infants is affected by mode of delivery, and relate differences in colonisation patterns to the maturation of a balanced Th1/Th2 immune response. Design The postnatal intestinal colonisation pattern was investigated in 24 infants, born vaginally (15) or by CS (nine). The intestinal microbiota were characterised using pyrosequencing of 16S rRNA genes at 1 week and 1, 3, 6, 12 and 24 months after birth. Venous blood levels of Th1- and Th2-associated chemokines were measured at 6, 12 and 24 months. Results Infants born through CS had lower total microbiota diversity during the first 2 years of life. CS delivered infants also had a lower abundance and diversity of the Bacteroidetes phylum and were less often colonised with the Bacteroidetes phylum. Infants born through CS had significantly lower levels of the Th1-associated chemokines CXCL10 and CXCL11 in blood. Conclusions CS was associated with a lower total microbial diversity, delayed colonisation of the Bacteroidetes phylum and reduced Th1 responses during the first 2 years of life.

Low gut microbiota diversity in early infancy precedes asthma at school age

Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age.

Probiotic Lactobacilli in Breast Milk and Infant Stool in Relation to Oral Intake During the First Year of Life

Objectives:This is to identify factors affecting the prevalence of Lactobacillus reuteri in maternal faeces and breast milk and infant faeces after oral supplementation with L reuteri and to assess the influence on microbial ecology, particularly Clostridium difficile and Bifidobacterium colonization. Materials and Methods:In this double-blind trial, 232 mothers with a family history of atopic disease were randomized to a daily intake of either L reuteri American-type culture collection (ATCC) 55730 (1 × 108 colony-forming units [CFU]) or placebo for the last 4 weeks of pregnancy. Their babies then continued with the same study product daily from birth until 12 months of age. Bacterial counts and prevalence were assessed in maternal breast milk and faeces and infant faeces, using conventional cultivation methods. Results:The prevalence of L reuteri was higher during the first year of life in the stool samples from infants in the active as compared with the placebo-treated group. The highest prevalence was recorded at 5 to 6 days of age (82% in the treated vs 20% in the placebo group, P < 0.001). Lactobacillus reuteri was isolated from 12% and 2%, respectively, in the colostrum samples (P < 0.05). Breast-feeding seemed to reduce faecal L reuteri counts, although antibiotics did not influence the levels of L reuteri. The administration of L reuteri did not affect bifidobacteria or C difficile colonization. Conclusion:Lactobacillus reuteri may be detected in breast milk after oral supplementation to the mother and in almost all infants after oral supplementation during the first year of life, as well as occasionally in many untreated infants.

Low breast milk TGF-beta2 is induced by Lactobacillus reuteri supplementation and associates with reduced risk of sensitization during infancy.

The immunological composition of breast milk differs between mothers. The reasons for these differences and the consequences for the breast‐fed infants are poorly understood. The aim of this study was to evaluate the effect of probiotic Lactobacillus reuteri supplementation on the immunological composition of breast milk in relation to sensitization and eczema in the babies. Total IgA, secretory IgA (SIgA), TGF‐β1, TGF‐β2, IL‐10, TNF, soluble CD14 (sCD14), and Na/K ratios were analyzed in colostrum and mature milk obtained from women treated with L. reuteri (n = 54) or placebo (n = 55) from gestational week 36 until delivery. Bacteriological analyses of L. reuteri were performed in faecal samples of the mothers. The infants were followed prospectively for 2 yr regarding development of eczema and sensitization as defined by a positive skin prick test and/or circulating allergen‐specific IgE antibodies at 6, 12, and 24 months of age. Supplementation of L. reuteri during pregnancy was associated with low levels of TGF‐β2 and slightly increased levels of IL‐10 in colostrum. For TGF‐β2, this association was most pronounced in mothers with detectable L. reuteri in faeces. Infants receiving breast milk with low levels of TGF‐β2 were less likely to become sensitized during their first 2 yr of life. A similar trend was observed for development of IgE‐associated eczema. The levels of total IgA, SIgA, TGF‐β1, TNF, sCD14, and Na/K ratios in breast milk were not affected by the intake of L. reuteri. None of these parameters correlated with sensitization or development of eczema in the infant, except for high Na/K ratios that associated with increased risk of sensitization. Supplementation with L. reuteri during late pregnancy reduces breast milk levels of TGF‐β2, and low levels of this cytokine are associated with less sensitization and possibly less IgE‐associated eczema in breast‐fed infants.

A Th1/Th2-associated chemokine imbalance during infancy in children developing eczema, wheeze and sensitization

Background Analyses of circulating chemokines offer novel tools to investigate the T helper (Th)1/Th2 imbalance in allergic disease in vivo.

No effect of probiotics on respiratory allergies : a seven-year follow-up of a randomized controlled trial in infancy

Supplementation with the probiotic Lactobacillus reuteri reduced the incidence of IgE‐associated allergic disease in infancy. This treatment might therefore also reduce the risk of asthma and allergic rhinoconjunctivitis in school age.

Safety of D(-)-lactic acid producing bacteria in the human infant

INTRODUCTIONThe gut of human infants is normally rapidly colonized after birth, and this colonization is considered not only to form a protective barrier against pathogenic bacteria but also to direct maturation of the infant immune system (1,2). In recent years, exogenous preparations of probiotic

Gut microbiota and allergy: the importance of the pregnancy period

Limited microbial exposure is suggested to underlie the increase of allergic diseases in affluent countries, and bacterial diversity seems to be more important than specific bacteria taxa. Prospective studies indicate that the gut microbiota composition during the first months of life influences allergy development, and support the theory that factors influencing the early maturation of the immune system might be important for subsequent allergic disease. However, recent research indicates that microbial exposure during pregnancy may be even more important for the preventative effects against allergic disease. This review gives a background of the epidemiology, immunology, and microbiology literature in this field. It focuses on possible underlying mechanisms such as immune-regulated epigenetic imprinting and bacterial translocation during pregnancy, potentially providing the offspring with a pioneer microbiome. We suggest that a possible reason for the initial exposure of bacterial molecular patterns to the fetus in utero is to prime the immune system and/or the epithelium to respond appropriately to pathogens and commensals after birth.

Pre- and post-natal Lactobacillus reuteri supplementation decreases allergen responsiveness in infancy

We have previously shown that Lactobacillus reuteri supplementation from pregnancy week 36 and to the infant through the first year of life decreased the prevalence of IgE‐associated eczema at 2 years. The underlying immunological mechanisms are unknown, however.

The Time for a Confirmative Necrotizing Enterocolitis Probiotics Prevention Trial in the Extremely Low Birth Weight Infant in North America Is Now

T.A. has received honoraria for lectures and funding for a clinical trial (ClinicalM eta-analyses of prospective randomized controlled trials (RCTs) evaluating probiotics as a measure to prevent necrotizing enterocolitis (NEC) in very low birth weight (VLBW; <1500 g) infants provide encouraging results. The recent ProPrem study in Australia and New Zealand also showed a significant effect on NEC in neonatal units with a low NEC incidence attributable to high breast-feeding rate. Consequently, it has been argued that there is already evidence to warrant a change in clinical practice and in relevant clinical practice guidelines. Some neonatologists now claim that it is unethical not to offer this management option to parents. On the other hand, others have raised concerns about the methodological rigor of many of the RCTs that were included in these meta-analyses. Particularly important, there is insufficient evidence about the efficacy and safety of probiotics for preventing NEC in the extremely low birth weight (ELBW; <1000 g) infant, the most vulnerable patient group cared for in the neonatal intensive care unit (NICU) and the babies at greatest risk of developing NEC. Although probiotics have been approved byHealth Canada for treating irritable bowel syndrome in adults and for the prevention of antibiotic-associated diarrhea and by regulators in both Canada and the US for addition to term infant formula, there has been greater reluctance to support the introduction of probiotics in the NICU. This may relate, at least in part, to the fact thatmost of the primary data originate from studies conducted outside of North America. Research ethics boards have refused to support clinical trials in premature infants because of issues related to safety in providing live microorganisms to these relatively immune deficient subjects. NEC remains among the most devastating diseases encountered in premature infants. It is caused by an excessive inflammatory process in the intestinal mucosa that presents clinically with feeding intolerance, abdominal distention, and bloody stools. The incidence of definite NEC (Bell stage II-III) among VLBW infants is approximately 7%, but varies in different neonatal settings between 4% and 15% depending on factors, such as breast feeding rates and use of milk banks. The mortality rate in affected babies is as high as 15%-30%. The systemic proinflammatory response