Infant behavioral state and stool microbiome in infants receiving Lactocaseibacillus rhamnosus GG in formula: Randomized controlled trial

Authors: SHULMAN, ROBERT - Children'S Nutrition Research Center (CNRC); CHICHLOWWSKI, MACIEJ - Mead Johnson; GUTIERREZ OROZCO, FABIOLA - Mead Johnson; HARRIS, CHERYL - Mead Johnson; WAMPLER, JENNIFER - Mead Johnson; BOKULICH, NICHOLAS - Eth Zurich; BERSETH, CAROL - Mead Johnson

Submitted to: BMC Pediatrics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/26/2022
Publication Date: 10/7/2022
Citation: Shulman, R.J., Chichlowwski, M., Gutierrez Orozco, F., Harris, C.L., Wampler, J.L., Bokulich, N.A., Berseth, C.L. 2022. Infant behavioral state and stool microbiome in infants receiving Lactocaseibacillus rhamnosus GG in formula: Randomized controlled trial. BMC Pediatrics. 22. Article 580. https://doi.org/10.1186/s12887-022-03647-x.
DOI: https://doi.org/10.1186/s12887-022-03647-x

Interpretive Summary: The important role fo gut bacteria on health and disease is being increasingly recognized. Probiotics are bacteria that when ingested provide a health benefit. In this study we evaluated in young infants the impact of a specific type of bacteria that is thought to be a probiotic. We wanted to find out if providing this bacteria to infants with colic could improve their symptoms. Infants were fed formula either with or without the probiotic bacteria and their colic symptoms were measured. Colic symptoms improved in both groups over time but there was no difference in the amount of improvement between those who did versus those who did not receive the probiotic. That said, analysis of the stools showed that the probiotic bacteria could be recovered from the infants' stools and that it was not associated with any identifiable ill effects. Studies are needed to determine if there may have been other health benefits to this probiotic bacteria and to identify other bacteria that may have a probiotic effect that could be used safely for treatment of colic.

Technical Abstract: Our aim was to evaluate infant behavioral state, stool microbiome profile and calprotectin in infants with infantile colic receiving a partially hydrolyzed protein formula with or without added Lacticaseibacillus (formerly Lactobacillus) rhamnosus GG (LGG). In this single-center, double-blind, controlled, parallel, prospective study, term infants (14–28 days of age)identified with colic (using modified Wessel's criteria, cried and/or fussed >= 3 h/day for >= 3 days/week, in a one-week period) were randomized to receive one of two formulas over a three-week feeding period, marketed partially hydrolyzed cow's milk-based infant formula (PHF, n = 35) or a similar formula with added LGG(PHF-LGG,n = 36). Parent reported infant behavior was recorded at three time points (Study Days 2–4, 10–12, and 18–20). Duration(hours/day)of crying/fussing(averaged over each three-day period)was the primary outcome. Stool samples were collected at Baseline and Study End (Days 19–21) to determine stool LGG colonization(by qPCR)and microbial abundance(using 16S rRNA gene sequencing)and calprotectin(ug/g). Duration of crying/fussing(mean +/- SE)decreased and awake/content behavior increased over time with no significant group differences over the course of the study. There were no group differences in the percentage of infants who experienced colic by study end. Colic decreased by Study End vs Baseline in both groups. Change in fecal calprotectin also was similar between groups. Comparing Study End vs Baseline, LGG abundance was greater in the PHF-LGG group (P < 0.001) whereas alpha diversity was greater in the PHF group (P = 0.022). Beta diversity was significantly different between PHF and PHF-LGG at Study End (P = 0.05). By study end, relative abundance of L. rhamnosus was higher in the PHF-LGG vs PHF group and vs Baseline. In this pilot study of infants with colic, both study formulas were well tolerated. Crying/fussing decreased and awake/content behavior increased in both study groups over the course of the study. Study results demonstrate a successful introduction of the probiotic to the microbiome. The partially hydrolyzed protein formula with added LGG was associated with significant changes in the gut microbiome.