Ellen E. Stobberingh

OBJECTIVE: The aim of this study was to examine the contribution of a broad range of external influences to the gut microbiotic composition in early infancy. METHODS: Fecal samples from 1032 infants at 1 month of age, who were recruited from the KOALA Birth Cohort Study in the Netherlands, were subjected to quantitative real-time polymerase chain reaction assays for the enumeration of bifidobacteria, Escherichia coli, Clostridium difficile, Bacteroides fragilis group, lactobacilli, and total bacterial counts. Information on potential determinants of the gut microbiotic composition was collected with repeated questionnaires. The associations between these factors and the selected gut bacteria were analyzed with univariate and multivariate analyses. RESULTS: Infants born through cesarean section had lower numbers of bifidobacteria and Bacteroides, whereas they were more often colonized with C difficile, compared with vaginally born infants. Exclusively formula-fed infants were more often colonized with E coli, C difficile, Bacteroides, and lactobacilli, compared with breastfed infants. Hospitalization and prematurity were associated with higher prevalence and counts of C difficile. Antibiotic use by the infant was associated with decreased numbers of bifidobacteria and Bacteroides. Infants with older siblings had slightly higher numbers of bifidobacteria, compared with infants without siblings. CONCLUSIONS: The most important determinants of the gut microbiotic composition in infants were the mode of delivery, type of infant feeding, gestational age, infant hospitalization, and antibiotic use by the infant. Term infants who were born vaginally at home and were breastfed exclusively seemed to have the most "beneficial" gut microbiota (highest numbers of bifidobacteria and lowest numbers of C difficile and E coli).

BACKGROUND: Greater use of antibiotics during the past 50 years has exerted selective pressure on susceptible bacteria and may have favoured the survival of resistant strains. Existing information on antibiotic resistance patterns from pathogens circulating among community-based patients is substantially less than from hospitalized patients on whom guidelines are often based. We therefore chose to assess the relationship between the antibiotic resistance pattern of bacteria circulating in the community and the consumption of antibiotics in the community. METHODS: Both gray literature and published scientific literature in English and other European languages was examined. Multiple regression analysis was used to analyse whether studies found a positive relationship between antibiotic consumption and resistance. A subsequent meta-analysis and meta-regression was conducted for studies for which a common effect size measure (odds ratio) could be calculated. RESULTS: Electronic searches identified 974 studies but only 243 studies were considered eligible for inclusion by the two independent reviewers who extracted the data. A binomial test revealed a positive relationship between antibiotic consumption and resistance (p < .001) but multiple regression modelling did not produce any significant predictors of study outcome. The meta-analysis generated a significant pooled odds ratio of 2.3 (95% confidence interval 2.2 to 2.5) with a meta-regression producing several significant predictors (F(10,77) = 5.82, p < .01). Countries in southern Europe produced a stronger link between consumption and resistance than other regions. CONCLUSIONS: Using a large set of studies we found that antibiotic consumption is associated with the development of antibiotic resistance. A subsequent meta-analysis, with a subsample of the studies, generated several significant predictors. Countries in southern Europe produced a stronger link between consumption and resistance than other regions so efforts at reducing antibiotic consumption may need to be strengthened in this area. Increased consumption of antibiotics may not only produce greater resistance at the individual patient level but may also produce greater resistance at the community, country, and regional levels, which can harm individual patients.

BACKGROUND AND AIMS: Perturbations in intestinal microbiota composition due to lifestyle changes may be involved in the development of atopic diseases. We examined gut microbiota composition in early infancy and the subsequent development of atopic manifestations and sensitisation. METHODS: The faeces of 957 infants aged 1 month and participating in the KOALA Birth Cohort Study were analysed using quantitative real-time PCR. Information on atopic symptoms (eczema, wheeze) and potential confounders was acquired through repeated questionnaires. Total and specific IgE were measured in venous blood samples collected during home visits when the infant was 2 years old. During these home visits a clinical diagnosis of atopic dermatitis was made according to the UK-Working Party criteria. RESULTS: The presence of Escherichia coli was associated with a higher risk of developing eczema (OR(adj) = 1.87; 95% CI 1.15 to 3.04), this risk being increased with increasing numbers of E coli (p(for trend) = 0.016). Infants colonised with Clostridium difficile were at higher risk of developing eczema (OR(adj) = 1.40; 95% CI 1.02 to 1.91), recurrent wheeze (OR(adj) = 1.75; 95% CI 1.09 to 2.80) and allergic sensitisation (OR(adj) = 1.54; 95% CI 1.02 to 2.31). Furthermore, the presence of C difficile was also associated with a higher risk of a diagnosis of atopic dermatitis during the home visit (OR(adj) = 1.73; 95% CI 1.08 to 2.78). CONCLUSION: This study demonstrates that differences in gut microbiota composition precede the development of atopy. Since E coli was only associated with eczema and C difficile was associated with all atopic outcomes, the underlying mechanisms explaining these association may be different.