Early-life antibiotic use is associated with increased risk for metabolic and immunological diseases, and mouse studies indicate a causal role of the disrupted microbiome. However, little is known about the impacts of antibiotics on the developing microbiome of children. Here we use phylogenetics, metagenomics and individual antibiotic purchase records to show that macrolide use in 2–7 year-old Finnish children (N=142; sampled at two time points) is associated with a long-lasting shift in microbiota composition and metabolism. The shift includes depletion of Actinobacteria, increase in Bacteroidetes and Proteobacteria, decrease in bile-salt hydrolase and increase in macrolide resistance. Furthermore, macrolide use in early life is associated with increased risk of asthma and predisposes to antibiotic-associated weight gain. Overweight and asthmatic children have distinct microbiota compositions. Penicillins leave a weaker mark on the microbiota than macrolides. Our results support the idea that, without compromising clinical practice, the impact on the intestinal microbiota should be considered when prescribing antibiotics.

OBJECTIVE: Antibiotics have direct effects on the human intestinal microbiota, particularly in infancy. Antibacterial agents promote growth in farm animals by unknown mechanisms, but little is known about their effects on human weight gain. Our aim was to evaluate the impact of antibiotic exposure during infancy on weight and height in healthy Finnish children. METHODS:The population-based cohort comprised 6114 healthy boys and 5948 healthy girls having primary care weight and height measurements and drug purchase data from birth to 24 months. BMI and height, expressed as z-scores at the median age of 24 months (interquartile range 24 to 26 months), were compared between children exposed and unexposed to antibiotics using analysis of covariance with perinatal factors as covariates.RESULTS: Exposed children were on average heavier than unexposed children (adjusted BMI-forage z-score difference in boys 0.

Both prenatal and post-natal exposure to antibiotics was associated with an increased risk of asthma. The potential role of adverse effects of antibiotics on the gut microbiota and the development of asthma should be further explored.

To determine whether childhood exposure to antibiotics is associated with the risk of developing inflammatory bowel disease (IBD), the authors conducted a national, register-based study comprising all children born in 1994-2008 in Finland and diagnosed with IBD by October 2010. The authors identified 595 children with IBD (233 with Crohn's disease and 362 with ulcerative colitis) and 2,380 controls matched for age, gender, and place of residence. The risk of pediatric Crohn's disease increased with the number of antibiotic purchases from birth to the index date and persisted when the 6 months preceding the case's diagnosis were excluded (for 7-10 purchases vs. none, odds ratio = 3.48, 95% confidence interval: 1.57, 7.34; conditional logistic regression). The association between Crohn's disease and antibiotic use was stronger in boys than in girls (P = 0.01). Cephalosporins showed the strongest association with Crohn's disease (for 3 purchases vs. nonuse, odds ratio = 2.82, 95% confidence interval: 1.65, 4.81). Antibiotic exposure was not associated with the development of pediatric ulcerative colitis. Repeated use of antibiotics may reflect shared susceptibility to childhood infections and pediatric Crohn's disease or alternatively may trigger disease development.

To the best of our knowledge, these figures for proven coeliac disease are the highest reported. Increased alertness to the condition and active case finding has made this efficient diagnostics possible.

Both maternal and child's use of antibiotics were associated with an increased risk of cow's milk allergy. Future studies are needed to confirm these novel findings and to explore the potential biologic mechanisms behind the association.

OBJECTIVE. Patients with inflammatory bowel disease (IBD) are at increased risk of certain cancers. We assessed the long-term risks of malignancies among patients with IBD in Finland. METHODS. A total of 21,964 patients with IBD (16,649 with UC and 5315 with CD) from the database of the Social Insurance Institution were diagnosed in the periods 1987-1993 and 2000-2007 and followed up to the end of 2010 in a linkage with the nationwide Finnish Cancer Registry. The numbers of cancers observed were compared to those expected in general population and expressed as a standardized incidence ratio (SIR). RESULTS. Overall, male patients with CD and UC had a slightly increased risk of malignancies. Patients with UC were found to have an increased risk of colon (SIR 1.81, 95% confidence interval 1.46-2.21), rectal (1.76, 1.35-2.25), biliary tract (7.26, 4.37-11.1), and thyroid cancers (1.93, 1.28-2.79). The risk of colorectal cancer (CRC) was highest among the youngest UC patients. Patients with CD had a significantly increased SIR for cancers of the small intestine (9.97, 4.30-19.6), anus (9.51, 1.96-27.8), and biliary tract (4.93, 1.02-14.4), and also for myeloma (2.84, 1.14-5.85). In addition, the risk of basal cell skin cancer was increased in IBD (1.29, 1.16-1.43). Males with UC had a slightly decreased risk of lung and prostate cancers. CONCLUSIONS. The incidence of cancer among male patients with CD and CU was higher than that in general population. Patients with UC are at increased risk for CRC and biliary tract cancers. CRC risk was highest in the youngest patients.

The association between celiac disease and malignancies is well recognized. In Finland, the prevalence of clinically diagnosed adult celiac disease is 0.6 % . In this large, population-based cohort, we aimed at a realistic projection of the cancer risk. METHODS:In the period 2002 -2011, the register comprised 32,439 adult celiac patients. This was linked with the Finnish Cancer Registry, which covers over 98 % of diagnosed malignancies. The standardized incidence ratio (SIR) was calculated for the malignancies, on the basis of incidence fi gures for the whole population. A time-stratifi ed analysis was made in celiac patients diagnosed after 2004 ( n = 11,991). Lifestyle factors, including smoking habits and obesity, were not obtainable. RESULTS:The overall incidence ratio of malignant diseases was not increased (SIR 0.94; 95 % confi dence intervals 0.89 -0.98), but it was ≥ 5 years from the diagnosis of celiac disease (1.31, 1.04 -1.63). The SIRs for non-Hodgkin lymphoma (NHL; 1.94; 1.62 -2.29), small-intestinal cancer (4.29; 2.83 -6.24), colon cancer (1.35; 1.13 -1.58), and basal cell carcinoma of the skin (1.13; 1.03 -1.22) were increased, whereas those for lung cancer (0.60; 0.48 -0.74), pancreatic cancer (0.73; 0.53 -0.97), bladder cancer (0.53; 0.35 -0.77), renal cancer (0.72; 0.51 -0.99), and breast cancer (0.70; 0.62 -0.79) were decreased. SIR for NHL immediately after the diagnosis of celiac disease was 2.56 (1.37 -4.38).CONCLUSIONS: There was no increased SIR of cancer in the whole series, but SIR was increased after 5 years from the diagnosis of celiac disease. The risk of breast and lung cancers was decreased. The risk of small-intestinal cancer and NHL was increased, but to a lesser extent than previously described.