Lactulose-Any Clinical Benefits beyond Constipation Relief? A Pilot Study in Infants with Allergic Symptoms

Abstract

The gastrointestinal tract of the newborn is sterile at birth. The maturation of the gut immune defence mechanisms is strongly influenced by the establishment of the gut microbiota (7). The compositional development of the normal microbiota in the intestine is influenced by the diet; in breast-fed infants more bifidobacteria and fewer enterobacteria, clostridia, enterococci and bacteroides are present when compared to formula-fed infants (10). It is also influenced by the child's condition, for example allergy and infection (3, 8). The gut microbiota differs between healthy and allergic children. Conversely, early intestinal colonization has recently been shown to affect the development of atopy; infants in whom atopy was developing had fewer bifidobacteria and more clostridia in their stools than those in whom atopy was not developing (9). The early establishment of a bifidobacterial flora, e.g. as supported by breastfeeding, would thus appear to be crucial in host protection. Modification of the gut microbiota may thus be taken as treatment and prophylactic target at an early age. Lactulose has been shown to modify the gut microbiota of adults in increasing bifidobacteria and lactobacilli and reducing the number of clostridia (5). In this pilot study we investigated whether the microbiota could be correspondingly modified in young infants with atopic manifestations with or without gastrointestinal symptoms, and whether such modification may be linked with alleviation of these symptoms. For this purpose, lactulose, 3 g twice a day, was administered and gastrointestinal and skin symptoms followed. The trial involved 12 infants aged 1-36 months (mean 9 months) who had at least one close relative (mother, father, sibling) with atopic eczema, allergic rhinitis or asthma. They had been admitted for evaluation of atopic skin manifestations with or without gastrointestinal symptoms (vomiting, diarrhea, abdominal pain). The criteria for atopic eczema included at least 3 out of 4 major features: pruritus, typical morphology and distribution of eczema, chronic or recurrent dermatitis, and a family history of atopy. The study protocol was approved by the Committee on Ethical Practice of Turku University Central Hospital and infants were enrolled in the study after written informed consent was obtained from their parents. The subjects were given lactulose (Duphalac, Solvay Pharmaceuticals, GmbH, Hannover) 3 g twice per day for three weeks. The diet of all infants was unchanged during this period and included either breast milk or a hypo-allergenic formula with age-appropriate solids (e.g. potato, rice, corn, fruits and berries, e.g. banana, pear and blueberry). They were clinically examined before and after treatment. The clinical condition of all infants was followed by means of a symptom chart monitoring skin eruptions and specifically gastrointestinal symptoms (vomiting, diarrhea, abdominal pain) for one week before enrolment and after the intervention. The severity of atopic eczema (extent and intensity) was evaluated using the SCORAD Index (4). Fecal samples were also collected before and after the treatment. Some of the predominant bacterial genera were analyzed by fluorescence in situ hybridization (FISH) with 16S rRNA specific oligonucleotide probes (1). The numbers of gut microbiota bacteria were compared by Wilcoxon Signed Rank Test. Altogether 7/10 children envinced active skin symptoms; SCORAD 7.64 (mean), 9.00 (SD) and 8/10 had gastrointestinal symptoms in the beginning of the pilot study. Skin symptoms included pruritus, erythema, *Corresponding author . Mailing address: The University of Turku, Functional Foods Forum, Itainen Pitkakatu 4A, 5th floor, 20520 Turku, Finland.