PurposeCurrently, there is no consensus concerning the possible beneficial colonic and systemic effects of prebiotic-containing infant formula. This study assesses whether the feeding of a galactooligosaccharides (GOS)-containing infant formula (0.44 g/dl of GOS) and the subsequent feeding of a GOS-containing follow-on formula (0.50 g/dl of GOS) have a prebiotic effect on intestinal microbiota that helps to decrease infections and allergy manifestations in healthy infants during the first year of life.MethodsA multicentre, randomised, double-blind and placebo-controlled trial was carried out on 365 healthy term infants enrolled before 8 weeks of age and randomly assigned to a formula with or without GOS, until 12 months of age. The incidence of infections and allergy manifestations, the antibiotics prescribed and faecal characteristics were recorded up to 12 months of age, while faecal samples were collected up to 4 months for the measurement of secretory immunoglobulin A, short-chain fatty acids and microbiota.ResultsA prebiotic effect on the faecal analysis was observed at 4 months of life. The GOS group showed a lower faecal pH (P = 0.019), a lower decreasing trend in secretory immunoglobulin A (P = 0.078), lower butyric acid concentration (P = 0.040) and an increase in Bifidobacterium counts (P = 0.010). Changes in faecal characteristics involved greater frequency (P < 0.001) and softer consistency (P < 0.05). The incidence of infections or allergic manifestations during the first year of life was similar in both groups, with no statistical differences (P > 0.05).ConclusionsThe feeding of GOS-containing infant formula produced a definite prebiotic effect consisting of changes in faecal composition and microbiota, and in faecal consistency and the frequency of defaecation. No changes in the incidence of infection or allergic manifestation during the first year of life were observed.

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Phenylketonuria (PKU), the most common inborn error of amino acid metabolism, is caused by mutations in the phenylalanine-4-hydroxylase (PAH) gene. This study aimed to assess the genotype-phenotype correlation in the PKU Spanish population and the usefulness in establishing genotype-based predictions of BH4 responsiveness in our population. It involved the molecular characterization of 411 Spanish PKU patients: mild hyperphenylalaninemia non-treated (mild HPA-NT) (34%), mild HPA (8.8%), mild-moderate (20.7%) and classic (36.5%) PKU. BH4 responsiveness was evaluated using a 6R-BH4 loading test. We assessed genotype-phenotype associations and genotype-BH4 responsiveness in our population according to literature and classification of the mutations. The mutational spectrum analysis showed 116 distinct mutations, most missense (70.7%) and located in the catalytic domain (62.9%). The most prevalent mutations were c.1066-11G>A (9.7%), p.Val388Met (6.6%) and p.Arg261Gln (6.3%). Three novel mutations (c.61-13del9, p.Ile283Val and p.Gly148Val) were reported. Although good genotype-phenotype correlation was observed, there was no exact correlation for some genotypes. Among the patients monitored for the 6R-BH4 loading test: 102 were responders (87, carried either one or two BH4-responsive alleles) and 194 non-responders (50, had two non-responsive mutations). More discrepancies were observed in non-responders. Our data reveal a great genetic heterogeneity in our population. Genotype is quite a good predictor of phenotype and BH4 responsiveness, which is relevant for patient management, treatment and follow-up.

The most important factor in the maintenance of the integrity of epithelial barrier function is probably the delivery of nutrients in the gastrointestinal tract. The role of the different ingredients added should be clarified.

Lipodystrophies are a group of diseases mainly characterized by a loss of adipose tissue and frequently associated with insulin resistance, hypertriglyceridemia, and hepatic steatosis. In uncommon lipodystrophies, these complications frequently are difficult to control with conventional therapeutic approaches. This retrospective study addressed the effectiveness of recombinant methionyl leptin (metreleptin) for improving glucose metabolism, lipid profile, and hepatic steatosis in patients with genetic lipodystrophic syndromes. We studied nine patients (five females and four males) with genetic lipodystrophies [seven with Berardinelli-Seip syndrome, one with atypical progeroid syndrome, and one with type 2 familial partial lipodystrophy (FPLD)]. Six patients were children under age 9 years, and all patients had baseline triglycerides levels [2.26 mmol/L and hepatic steatosis; six had poorly controlled diabetes mellitus. Metreleptin was self-administered subcutaneously daily at a final dose that ranged between 0.05 and 0.24 mg/(kg day) [median: 0.08 mg/ (kg day)] according to the body weight. The duration of treatment ranged from 9 months to 5 years, 9 months (median: 3 years). Plasma glucose, hemoglobin A1c (Hb A1c), lipid profile, plasma insulin and leptin, and hepatic enzymes were evaluated at baseline and at least every 6 months. Except for the patient with FPLD, metreleptin replacement significantly improved metabolic control (Hb A1c: from 10.4 to 7.1 %, p \ 0.05). Plasma triglycerides were reduced 76 % on average, and hepatic enzymes decreased more than 65 %. This study extends knowledge about metreleptin replacement in genetic lipodystrophies, bearing out its effectiveness for long periods of time.