Metabolic profiling in children with autism spectrum disorder with and without mental regression: preliminary results from a cross-sectional case-control study.

INTRODUCTION: It is challenging to establish the mechanisms involved in the variety of well-defined clinical phenotypes in autism spectrum disorder (ASD) and the pathways involved in their pathogeneses. OBJECTIVES: The aim of the present study was to evaluate the metabolomic profiles of children with ASD subclassified by mental regression (AR) phenotype and with no regression (ANR). METHODS: The present study was a cross-sectional case-control study. Thirty children aged 2-6 years with ASD were included: 15 with ANR and 15 with AR. In addition, a control group of 30 normally developing children was selected and matched to the ASD group by sex and age. Plasma samples were analyzed with a metabolomics single platform methodology based on liquid chromatography-mass spectrometry. Univariate and multivariate analysis, including orthogonal partial least squares-discriminant analysis modeling and Shared-and-Unique-Structures plots, were performed using MetaboAnalyst 4.0 and SIMCA-P 15. The primary endpoint was the metabolic signature profiling among healthy children and autistic children and their subgroups. RESULTS: Metabolomic profiles of 30 healthy children, 15 ANR and 15 AR were compared. Several differences between healthy children and children with ASD were detected, involving mainly amino acid, lipid and nicotinamide metabolism. Furthermore, we report subtle differences between the ANR and AR groups. CONCLUSIONS: In this study, we report, for the first time, the plasmatic metabolomic profiles of children with ASD, including two different phenotypes based on mental regression status. The use of a liquid chromatography-mass spectrometry platform approach for metabolomics in ASD children using plasma appears to be very efficient and adds further support to previous findings in urine. Furthermore, the present study documents several changes related to amino acid, NAD+ and lipid metabolism that, in some cases, such as arginine and glutamate pathway alterations, seem to be associated with the AR phenotype. Further targeted analyses are needed in a larger cohort to validate the results presented herein.

Evaluation of the safety, tolerance and efficacy of 1-year consumption of infant formula supplemented with Lactobacillus fermentum CECT5716 Lc40 or Bifidobacterium breve CECT7263: a randomized controlled trial.

BACKGROUND: The microorganism present in breast milk, added to other factors, determine the colonization of infants. The objective of the present study is to evaluate the safety, tolerance and effects of the consumption of a milk formula during the first year of life that is supplemented with L. fermentum CECT5716 or Bifidobacterium breve CECT7263, two strains originally isolated from breast milk. METHODS: A randomized, double blind, controlled, parallel group study including healthy, formula-fed infants was conducted. Two hundred and thirty-six 1-month-old infants were selected and randomly divided into three study groups according to a randomization list. Infants in the control group received a standard powdered infant formula until 12 months of age. Infants in the probiotic groups received the same infant formula but supplemented with L. fermentum CECT5716 Lc40 or B. breve CECT7263. Main outcome was weigh-gain of infants as safety marker. RESULTS: One hundred and eighty-nine infants completed the eleven months of intervention (61 in control group, 65 in Lf group and 63 in Bb group). The growth of infants in the three groups was consistent with standards. No significant differences were observed in the main outcome, weight-gain (Control group: 5.77 Kg ± 0.95, Lf group: 5.77 Kg ± 1.31, Bb group: 5.58 Kg ± 1.10; p = 0.527). The three milk formulae were well tolerated, and no adverse effects were related to the consumption of any of the formula. Infants receiving B. breve CECT7263 had a 1.7 times lower risk of crying than the control group (OR = 0.569, CI 95% 0.568-0.571; p = 0.001). On the other hand, the incidence of diarrhoea in infants receiving the formula supplemented with L. fermentum CECT5716 was a 44% lower than in infants receiving the control formula (p = 0.014). The consumption of this Lactobacillus strain also reduced the duration of diarrhoea by 2.5 days versus control group (p = 0.044). CONCLUSIONS: The addition of L. fermentum CECT5716 Lc40 or B. breve CECT7263, two probiotic strains naturally found in breast milk, to infant formulae is safe and induces beneficial effects on the health of infants. TRIAL REGISTRATION: The trial was retrospectively registered in the US Library of Medicine ( www.clinicaltrial.gov ) with the number NCT03204630 . Registered 11 August 2016.

Long-term safety of early consumption of Lactobacillus fermentum CECT5716: A 3-year follow-up of a randomized controlled trial.

Lactobacillus fermentum CECT5716 is a probiotic strain originally isolated from human breast milk. Previous clinical studies in infants showed that the early administration of a milk formula containing this probiotic strain was safe and may be useful for the prevention of community-acquired infections. This is a 3-year follow-up study aimed at evaluating the long-term effects produced by the early consumption of an infant formula supplemented with L. fermentum CECT5716 (experimental group, EG) compared with a control formula without the probiotic (control group, CG). The infants included in this follow-up study had previously completed a 5-month randomized double-blind controlled trial (from 1 to 6 months of age), where the safety and tolerance of the probiotic formula was evaluated. The main outcome of the follow-up study was the growth of the children. The secondary outcomes included the incidence of infectious and non-infectious diseases, parameters related with intestinal function and faecal microbiota. At 3 years, the mean values of weight, length and head circumference were similar in children of the EG compared with those of the CG. No differences were observed in the incidence of infectious and non-infectious diseases or disorders related with intestinal function. The pattern of faecal microbiota was also similar between both groups. In conclusion, this 3-year study shows that the early administration of the probiotic of L. fermentum CECT5716 in an infant formula is safe and it does not produce measurable differences in children compared with a control formula.