The role of microbiota on infantile colic

Editor(s): Rodrigo Vázquez Frias.

Key Messages

• Growing scientific evidence suggests a link between the alterations in microbiota and infant colic.

• Limosilactobacillus (L) reuteri (previously known as Lactobacillus reuteri*) DSM17938 is the probiotic strain with the highest evidence of efficacy and can be recommended for breastfed infants with infant colic.

• Partially hydrolyzed formula may offer some useful alternative to intact protein in the dietary management of infant colic, but more randomized controlled trials are needed to support its efficacy.

The amount and pattern of infant crying are age-dependent and change during the first months of life. There is an increased duration of crying in the first weeks of life, reaching a maximum between 6 and 8 weeks of age and then declining to more stable levels around 12 weeks of age.[1] The Rome IV criteria has drastically reviewed the clinical definition of infant colic (IC). According to it, infant colic occurs if 1) an infant is less than 5 months of age when the symptoms start and stop; 2) recurrent and prolonged periods of infant crying, fussing, or irritability reported by caregivers that occur without obvious cause and cannot be prevented or resolved by caregivers; and 3) has no evidence of failure to thrive, fever, or illness.[2] All of the above should be present to diagnose infant colic. IC occurs in both breast-fed and formula-fed infants.[3] The etiology of IC is suggested to be multifactorial such as gastrointestinal, psychosocial, and neurodevelopmental, with increasing importance of the role of intestinal microbiome. Several studies have reported an association between IC and characteristics in intestinal microbiota such as lower bacterial diversity, higher abundance of Proteobacteria and lower abundance of Bifidobacterium and Lactobacillus.[4] The clinical management of infant colic includes: parental education, reassurance and empathy provided by the physician; modification of infant care and environmental routines. The treatment with pharmacological agents, like simethicone or lactase, is not supported by clinical evidence; while the use of certain probiotic strains may be helpful.[1]

Amongst the few probiotic strains used in the treatment of infant colic, Limosilactobacillus (L) reuteri (previously known as Lactobacillus reuteri*) DSM 17938 has been the most studied. It inhibits pathogen growth and affects the immune system in different ways: through a modulatory effect of the pro-inflammatory signalling via Toll-like receptor 4 (TLR4) and nuclear factor-B (NF-B), resulting in decreased mucosal pro-inflammatory cytokines such as tumour necrosis factor-α (TNF–α) and interleukin-1β (IL-1β). Also, it modulates the composition of intestinal immune cells in neonatal gut, including dendritic cells and regulatory T cells.5 According to ameta-analysis, using data from 4 double-blind trials, including 345 infants with colic, L. reuteri DSM 17938 is effective and can be recommended for treatment of breastfed infants with colic.[6] In addition to that, a recent study, not included in the meta-analysis, has shown that infants with colic treated with L. reuteri DSM 17938 for 30 days not only significantly decreased crying time, but also had confirmed reduction in faecal calprotectin and RORg/FOXP3 ratio, supporting the hypothesis of probiotic induced local and systemic reduction in inflammation.[7] More studies are needed for better understanding of the efficacy mechanism of probiotics in infant colic.

There is evidence suggesting that partially hydrolyzed formula (pHF) use in non-exclusively breastfed infants maybe associated with decreased colic incidence compared with infants, fed intact protein infant formula.[1,8] pHF may offer some useful alternative to intact protein in the dietary management of common FGIDs, although well-designed, randomized trials are needed to allow to recommend the use of pHF for treatment in infants with FGIDs.[9]

1.  Zeevenhooven J, Brownie PD, L’Hoir MP, de Weerth C, Benninga MA. Infant colic: mechanisms and management. Nat Rev Gastroenterol Hepatol 2018;15:479–96.
2.  Benninga MA, Nurko S, Faure Ch, Hyman PE, St James–Roberts I, Schechter NL. Childhood Functional Gastrointestinal Disorders: Neonate/ Toddler. Gastroenterology 2016;150:1443–55.
3.  Lucas A, St James–Roberts I. Crying, fussing and colic behaviour in breast- and bottle-fed infants. Early Human Development 1998;53(1),9–18.
4.  Dubois NE, Gregory KE. Characterizing the Intestinal Microbiome in Infantile Colic: Findings Based on an Integrative Review of the Literature. Biol Res Nurs 2016;18(3):307–15. doi:10.1177/1099800415620840
5.  Hoang TK, Freeborn J, Wang T, Mai T, He B, Park S, et al. Human Breast Milk Promotes the Immunomodulatory Function of Probiotic Lactobacillus reuteri DSM 17938 in the Neonatal Rat Intestine. J Probiotics Health 2019;7(1). pii: 210.
6.  Sung V, D’Amico F, Cabana MD, Chau K, Koren G, Savino F, et al. Lactobacillus reuteri Treat Infant Colic: A Meta-analysis. Pediatrics 2018;141(1):e20171811. doi:10.1542/ peds.2017–1811
7.  Savino F, Garro M, Montanari P, Galliano I, Bergallo M. Crying Time and RORγ/FOXP3 Expression in Lactobacillus reuteri DSM17938- Treated Infants with Colic: A Randomized Trial. J Pediatr 2018;192:171–7
8.   Vandenplas Y, Latiff AHA, Fleischer DM, Gutiérrez-Castrellon P, Miqdady MIS, Smith P, et al. Partially hydrolyzed formula in non-exclusively breastfed infants: A systematic review and expert consensus. Nutrition 2019;57:268–74. doi:10.1016/j.nut.2018.05.018
9.  Vandenplas Y, Cruchet S, Faure C, Lee H, Di Lorenzo C, Staiano A, et al. Acta Paediatr 2014;103:689–95. doi: 10.1111/apa.12637