RESUMO
OBJECTIVE: To dissect potential confounding effects of breast milk and formula feeding on crying + fussing, fecal calprotectin, and gut microbiota in babies with colic. We hypothesized that infant colic is associated with gut inflammation linked to intestinal dysbiosis. STUDY DESIGN: A nested case-control design of 3 of our studies was used to analyze clinical and laboratory data at presentation, comparing babies with colic with controls. All investigators other than the biostatistician were blinded during data analysis. Subjects were recruited based on their age and crying + fussy time. We screened 65 infants, 37 with colic, as defined by Barr diary (crying + fussing time >3 hours daily), who were compared with 28 noncolicky infants. RESULTS: Fecal calprotectin was elevated in babies with colic. For each mode of infant feeding (breast milk, formula, or breast + formula), infants' fecal calprotectin was higher in babies with colic. Infants with colic had similar levels of fecal alpha diversity (richness) when compared with controls, and alpha diversity was lower in breast-fed babies. Beta diversity at the phylum level revealed significant differences in microbial population. A phylum difference resulted from reduced Actinobacteria (95% of which are Bifidobacilli) in babies with colic. Species significantly associated with colic were Acinetobacter and Lactobacillus iners. CONCLUSIONS: Colic is linked with gut inflammation (as determined by fecal calprotectin) and dysbiosis, independent of mode of feeding, with fewer Bifidobacilli. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01279265 and NCT01849991.
Assuntos
Cólica/complicações , Disbiose/diagnóstico , Fezes/química , Inflamação/diagnóstico , Complexo Antígeno L1 Leucocitário/análise , Acinetobacter/isolamento & purificação , Aleitamento Materno , Estudos de Casos e Controles , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal , Humanos , Lactente , Fórmulas Infantis , Recém-Nascido , Lactobacillus/isolamento & purificação , MasculinoRESUMO
OBJECTIVE: To assess the safety of probiotic Lactobacillus reuteri strain Deutsche Sammlung von Mikroorganismen (DSM) 17938 with daily administration to healthy infants with colic and to determine the effect of L reuteri strain DSM 17938 on crying, fussing, inflammatory, immune, and microbiome variables. STUDY DESIGN: We performed a controlled, double-blinded, phase 1 safety and tolerability trial in healthy breast-fed infants with colic, aged 3 weeks to 3 months, randomly assigned to L reuteri strain DSM 17938 (5 × 108 colony-forming units daily) or placebo for 42 days and followed for 134 days. RESULTS: Of 117 screened infants, 20 were randomized to L reuteri strain DSM 17938 or placebo (sunflower oil) (in a 2:1 ratio) with 80% retention. Eleven of the 20 (55%) presented with low absolute neutrophil counts (<1500/mm3), which resolved in all subjects by day 176. L reuteri strain DSM 17938 produced no severe adverse events and did not significantly change crying time, plasma bicarbonate, or inflammatory biomarkers. Fecal calprotectin decreased rapidly in both groups. In the infants with dominant fecal gram negatives (Klebsiella, Proteus, and Veillonella), resolution of colic was associated with marked decreases in these organisms. CONCLUSIONS: Daily administration of L reuteri strain DSM 17938 appears to be safe in newborn infants with colic, including those with neutropenia, which frequently coexists. A placebo response of 66% suggests that many infants with colic will have resolution within 3 weeks. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01849991.