Work package 1.2a and 1.2b

Hypothesis: Infant infection rates are associated with birth method, breast-feeding and antibiotics.

Antibiotics, breast-feeding and infections

The early diet and gut microbiota may have a critical role for later immunity and infection resistance. Most information is available from compromised infants but we need information from a standard Danish population. We therefore relate infant infections and gut microbiota to breast- and formula-feeding, and use of antibiotics around birth.

Methods

We establish an unselected population-based cohort with children, born year 2010-12 in Odense. Blood samples and questionnaire data are obtained from mothers at birth, 3 and 18 months of age. Clinical information includes delivery mode, vaccinations, antibiotics use and doctor and hospital visits. From a randomized clinical trial at Odense and Hvidovre Hospitals, we collect fecal content on days 1 and 10 from infants of mothers treated with antibiotics either before or after transection of the umbilical cord at caesarean delivery (e.g. with or without infant exposure to antibiotics).

Results

Relationships among later infections, mode of delivery, diet and antibiotics at birth are analyzed by multivariate regression analyses. Gut microbiota analyses will reveal if neonatal antibiotics exposure influences later gut colonization in infants.

Work package 1.2c

Hypothesis: Bovine colostrum given shortly before and after chemotherapy may protect against gastrointestinal toxicity and thereby reduce associated complications such as infections and inflammation.

Milk and immunity in children during chemotherapy

Pediatric Acute Lymphoblastic Leukaemia (ALL) is the most common form of childhood cancer. All actively proliferating tissues are affected by antineoplastic drugs including the gut. Gastrointestinal toxicity induced by chemotherapy is likely to play a key role in the pathogenesis of treatment related complications in chemotherapy treated children. Since the intestinal epithelium is in constant interaction with the gut microbiota it is essential for the maintenance of the immunological balance that the epithelial barrier is intact. Chemotherapy-induced toxicity may disturb this balance, and this may result in both infections and systemic inflammatory responses. Treatment with broad-spectrum antibiotics is required to reduce the risk of infections, but it is largely unknown if dietary factors may improve recovery from the cancer itself (e.g. leukemia) and chemotherapy-induced gut and systemic complications.

Methods

In the ALL patient studies, we investigate the effect of bovine colostrum on infections, gastrointestinal toxicity and systemic inflammation. The study is a randomized, double-blind placebo-controlled clinical study at the two hospital sites. Primary outcomes are days with fever, neutropenia and sepsis. Secondary outcomes are days given antibiotics and in intensive care, as well as clinical and paraclinical measures of gut toxicity and systemic inflammation. Finally, the faecal gut microbiota in children under chemotherapy is investigated.

In pig studies, newborn piglets are treated with clinically-relevant doses of chemotherapy and immunity parameters and gut functions are investigated. Subsequently, chemotherapy-treated piglets are fed with varying doses of bovine colostrum during chemotherapy and endpoints are measured.

Results

We expect that ingestion of sufficient amounts of bovine colostrum will improve parameters of gut, structure and function and the clinical responses to chemotherapy in both children and pigs.