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Published in: BMC Pediatrics 1/2022

Open Access 01-12-2022 | Probiotics | Research

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

Authors: Robert J. Shulman, Maciej Chichlowski, Fabiola Gutierrez Orozco, Cheryl L. Harris, Jennifer L. Wampler, Nicholas A. Bokulich, Carol Lynn Berseth

Published in: BMC Pediatrics | Issue 1/2022

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Abstract

Background

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).

Methods

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 (μg/g).

Results

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.

Conclusions

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.

Trial registration

ClinicalTrials.gov, ClinicalTrials.gov Identifier: NCT02340143. Registered 16/01/2015.
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Literature
10.
go back to reference Maldonado-Lobon JA, Blanco-Rojo R, Maldonado J, Ali MA, Almazan MV, Suanes-Cabello A, Callejon E, Jaldo R, Benavides MR, Negrillo AM, et al. Efficacy of Bifidobacterium breve CECT7263 for infantile colic treatment: an open-label, parallel, randomised, controlled trial. Benef Microbes. 2021;12(1):55–67. https://doi.org/10.3920/BM2020.0105.CrossRefPubMed Maldonado-Lobon JA, Blanco-Rojo R, Maldonado J, Ali MA, Almazan MV, Suanes-Cabello A, Callejon E, Jaldo R, Benavides MR, Negrillo AM, et al. Efficacy of Bifidobacterium breve CECT7263 for infantile colic treatment: an open-label, parallel, randomised, controlled trial. Benef Microbes. 2021;12(1):55–67. https://​doi.​org/​10.​3920/​BM2020.​0105.CrossRefPubMed
15.
go back to reference Zheng J, Wittouck S, Salvetti E, Franz C, Harris HMB, Mattarelli P, O’Toole PW, Pot B, Vandamme P, Walter J, et al. A taxonomic note on the genus Lactobacillus: description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae. Int J Syst Evol Microbiol. 2020;70(4):2782–858. https://doi.org/10.1099/ijsem.0.004107.CrossRefPubMed Zheng J, Wittouck S, Salvetti E, Franz C, Harris HMB, Mattarelli P, O’Toole PW, Pot B, Vandamme P, Walter J, et al. A taxonomic note on the genus Lactobacillus: description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae. Int J Syst Evol Microbiol. 2020;70(4):2782–858. https://​doi.​org/​10.​1099/​ijsem.​0.​004107.CrossRefPubMed
23.
go back to reference Iacovou M, Craig SS, Yelland GW, Barrett JS, Gibson PR, Muir JG. Randomised clinical trial: reducing the intake of dietary FODMAPs of breastfeeding mothers is associated with a greater improvement of the symptoms of infantile colic than for a typical diet. Aliment Pharmacol Ther. 2018;48(10):1061–73. https://doi.org/10.1111/apt.15007.CrossRefPubMed Iacovou M, Craig SS, Yelland GW, Barrett JS, Gibson PR, Muir JG. Randomised clinical trial: reducing the intake of dietary FODMAPs of breastfeeding mothers is associated with a greater improvement of the symptoms of infantile colic than for a typical diet. Aliment Pharmacol Ther. 2018;48(10):1061–73. https://​doi.​org/​10.​1111/​apt.​15007.CrossRefPubMed
25.
go back to reference Taubman B. Parental counseling compared with elimination of cow’s milk or soy milk protein for the treatment of infant colic syndrome: a randomized trial. Pediatrics. 1988;81(6):756–61.CrossRef Taubman B. Parental counseling compared with elimination of cow’s milk or soy milk protein for the treatment of infant colic syndrome: a randomized trial. Pediatrics. 1988;81(6):756–61.CrossRef
27.
go back to reference Lothe L, Lindberg T. Cow’s milk whey protein elicits symptoms of infantile colic in colicky formula-fed infants: a double-blind crossover study. Pediatrics. 1989;83(2):262–6.CrossRef Lothe L, Lindberg T. Cow’s milk whey protein elicits symptoms of infantile colic in colicky formula-fed infants: a double-blind crossover study. Pediatrics. 1989;83(2):262–6.CrossRef
28.
go back to reference Lothe L, Lindberg T, Jakobsson I. Cow’s milk formula as a cause of infantile colic: a double-blind study. Pediatrics. 1982;70(1):7–10.CrossRef Lothe L, Lindberg T, Jakobsson I. Cow’s milk formula as a cause of infantile colic: a double-blind study. Pediatrics. 1982;70(1):7–10.CrossRef
29.
go back to reference Scalabrin DM, Johnston WH, Hoffman DR, P’Pool VL, Harris CL, Mitmesser SH. Growth and tolerance of healthy term infants receiving hydrolyzed infant formulas supplemented with Lactobacillus rhamnosus GG: randomized, double-blind, controlled trial. Clin Pediatr (Phila). 2009;48(7):734–44. https://doi.org/10.1177/0009922809332682.CrossRef Scalabrin DM, Johnston WH, Hoffman DR, P’Pool VL, Harris CL, Mitmesser SH. Growth and tolerance of healthy term infants receiving hydrolyzed infant formulas supplemented with Lactobacillus rhamnosus GG: randomized, double-blind, controlled trial. Clin Pediatr (Phila). 2009;48(7):734–44. https://​doi.​org/​10.​1177/​0009922809332682​.CrossRef
31.
go back to reference Bazanella M, Maier TV, Clavel T, Lagkouvardos I, Lucio M, Maldonado-Gòmez MX, Autran C, Walter J, Bode L, Schmitt-Kopplin P, et al. Randomized controlled trial on the impact of early-life intervention with bifidobacteria on the healthy infant fecal microbiota and metabolome. Am J Clin Nutr. 2017;106(5):1274–86. https://doi.org/10.3945/ajcn.117.157529.CrossRefPubMed Bazanella M, Maier TV, Clavel T, Lagkouvardos I, Lucio M, Maldonado-Gòmez MX, Autran C, Walter J, Bode L, Schmitt-Kopplin P, et al. Randomized controlled trial on the impact of early-life intervention with bifidobacteria on the healthy infant fecal microbiota and metabolome. Am J Clin Nutr. 2017;106(5):1274–86. https://​doi.​org/​10.​3945/​ajcn.​117.​157529.CrossRefPubMed
35.
go back to reference Jacobi SK, Yatsunenko T, Li D, Dasgupta S, Yu RK, Berg BM, Chichlowski M, Odle J. Dietary isomers of sialyllactose increase ganglioside sialic acid concentrations in the corpus callosum and cerebellum and modulate the colonic microbiota of formula-fed piglets. J Nutr. 2015;146(2):200–8. https://doi.org/10.3945/jn.115.220152.CrossRefPubMed Jacobi SK, Yatsunenko T, Li D, Dasgupta S, Yu RK, Berg BM, Chichlowski M, Odle J. Dietary isomers of sialyllactose increase ganglioside sialic acid concentrations in the corpus callosum and cerebellum and modulate the colonic microbiota of formula-fed piglets. J Nutr. 2015;146(2):200–8. https://​doi.​org/​10.​3945/​jn.​115.​220152.CrossRefPubMed
39.
53.
54.
56.
go back to reference Navarro-Tapia E, Sebastiani G, Sailer S, Almeida Toledano L, Serra-Delgado M, García-Algar Ó, Andreu-Fernández V. Probiotic supplementation during the perinatal and infant period: effects on gut dysbiosis and disease. Nutrients. 2020;12(8):2243.CrossRef Navarro-Tapia E, Sebastiani G, Sailer S, Almeida Toledano L, Serra-Delgado M, García-Algar Ó, Andreu-Fernández V. Probiotic supplementation during the perinatal and infant period: effects on gut dysbiosis and disease. Nutrients. 2020;12(8):2243.CrossRef
63.
64.
go back to reference Koninckx CR, Donat E, Benninga MA, Broekaert IJ, Gottrand F, Kolho KL, Lionetti P, Miele E, Orel R, Papadopoulou A, et al. The use of fecal calprotectin testing in paediatric disorders: a position paper of the European Society for Paediatric Gastroenterology and Nutrition Gastroenterology Committee. J Pediatr Gastroenterol Nutr. 2021;72(4):617–40. https://doi.org/10.1097/mpg.0000000000003046.CrossRefPubMed Koninckx CR, Donat E, Benninga MA, Broekaert IJ, Gottrand F, Kolho KL, Lionetti P, Miele E, Orel R, Papadopoulou A, et al. The use of fecal calprotectin testing in paediatric disorders: a position paper of the European Society for Paediatric Gastroenterology and Nutrition Gastroenterology Committee. J Pediatr Gastroenterol Nutr. 2021;72(4):617–40. https://​doi.​org/​10.​1097/​mpg.​0000000000003046​.CrossRefPubMed
Metadata
Title
Infant behavioral state and stool microbiome in infants receiving Lactocaseibacillus rhamnosus GG in formula: randomized controlled trial
Authors
Robert J. Shulman
Maciej Chichlowski
Fabiola Gutierrez Orozco
Cheryl L. Harris
Jennifer L. Wampler
Nicholas A. Bokulich
Carol Lynn Berseth
Publication date
01-12-2022
Publisher
BioMed Central
Keyword
Probiotics
Published in
BMC Pediatrics / Issue 1/2022
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-022-03647-x

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