The NEST | No. 46 | June 2020 www.nestlenutrition-institute.org

The role of microbiota Pain detection Crying on infantile colic Gut brain axis

Gut motility Intestinal Rodrigo Vázquez Frias permeability

Paediatric gastroenterologist and nutritionist at Hospital Infantil Gas production Gut low grade Figure 1: Possible de México Federico Gómez, Mexico City, Mexico. & gut distention inflammation mechanisms through which dysbiosis can [email protected] contribute excessive crying/colic. Adapted from Zeevenhooven J et al, 2018

The amount and pattern of infant reported an association between pro-inflammatory cytokines such Several studies References Key messages: crying are age-dependent and change IC and characteristics in intestinal as tumour necrosis factor-α 1. Zeevenhooven J, Brownie PD, L’Hoir MP, de during the first months of life. There is microbiota such as lower bacterial (TNF– ) and interleukin-1 (IL-1 ). Weerth C, Benninga MA. Infant colic: α β β among infants mechanisms and management. Nat Rev • Growing scientific evidence an increased duration of crying in the diversity, higher abundance of Also, it modulates the composition have reported an Gastroenterol Hepatol 2018;15:479–96. first weeks of life, reaching a maximum Proteobacteria and lower abundance of intestinal immune cells in neonatal 2.  Benninga MA, Nurko S, Faure Ch, Hyman PE, St suggests a link between James–Roberts I, Schechter NL. Childhood the alterations in microbiota between 6 and 8 weeks of age and of Bifidobacterium and Lactobacillus.4 gut, including dendritic cells and association between Functional Gastrointestinal Disorders: Neonate/ Toddler. Gastroenterology 2016;150:1443–55. 5 and infant colic. then declining to more stable levels The clinical management of infant regulatory T cells. According to a 3.  Lucas A, St James–Roberts I. Crying, fussing around 12 weeks of age.1 The Rome IV colic includes: parental education, meta-analysis, using data from 4 infant colic and and colic behaviour in breast- and bottle-fed • Limosilactobacillus (L) reuteri infants. Early Human Development criteria has drastically reviewed the reassurance and empathy provided double-blind trials, including 345 (previously known as Lactobacillus characteristics 1998;53(1),9–18. clinical definition of infant colic (IC). by the physician; modification of infant infants with colic, L. reuteri 4.  Dubois NE, Gregory KE. Characterizing the reuteri*) DSM17938 is the probiotic in intestinal Intestinal Microbiome in Infantile Colic: strain with the highest evidence of According to it, infant colic occurs if care and environmental routines. DSM 17938 is effective and can be Findings Based on an Integrative Review of the 1) an infant is less than 5 months of The treatment with pharmacological recommended for treatment Literature. Biol Res Nurs 2016;18(3):307–15. efficacy and can be recommended microbiota doi:10.1177/1099800415620840 6 for breastfed infants with infant age when the symptoms start and agents, like simethicone or lactase, of breastfed infants with colic. 5.  Hoang TK, Freeborn J, Wang T, Mai T, He B, Park S, et al. Human Breast Milk Promotes the colic. stop; 2) recurrent and prolonged is not supported by clinical evidence; In addition to that, a recent study, Immunomodulatory Function of Probiotic periods of infant crying, fussing, or while the use of certain probiotic not included in the meta-analysis, There is evidence suggesting that Lactobacillus reuteri DSM 17938 in the Neonatal • Partially hydrolyzed formula may Rat Intestine. J Probiotics Health 2019;7(1). irritability reported by caregivers that strains may be helpful.1 has shown that infants with colic partially hydrolyzed formula (pHF) pii: 210. offer some useful alternative to occur without obvious cause and treated with L. reuteri DSM 17938 use in non-exclusively breastfed 6.  Sung V, D’Amico F, Cabana MD, Chau K, Koren intact protein in the dietary G, Savino F, et al. Lactobacillus reuteri Treat cannot be prevented or resolved by Amongst the few probiotic strains for 30 days not only significantly infants maybe associated with Infant Colic: A Meta-analysis. Pediatrics management of infant colic, but 2018;141(1):e20171811. doi:10.1542/ caregivers; and 3) has no evidence used in the treatment of infant colic, decreased crying time, but also decreased colic incidence compared more randomized controlled trials peds.2017–1811 of failure to thrive, fever, or illness.2 Limosilactobacillus (L) reuteri had confirmed reduction in faecal with infants, fed intact protein infant 7.  Savino F, Garro M, Montanari P, Galliano I, are needed to support its efficacy. Bergallo M. Crying Time and ROR /FOXP3 1,8 γ All of the above should be present to (previously known as Lactobacillus calprotectin and RORg/FOXP3 ratio, formula. pHF may offer some useful Expression in Lactobacillus reuteri DSM17938- diagnose infant colic. IC occurs in reuteri*) DSM 17938 has been the most supporting the hypothesis of probiotic alternative to intact protein in the Treated Infants with Colic: A Randomized Trial. J Pediatr 2018;192:171–7 both breast-fed and formula-fed studied. It inhibits pathogen growth induced local and systemic reduction dietary management of common 8. Vandenplas Y, Latiff AHA, Fleischer DM, infants.3 The etiology of IC is in inflammation.7 More studies are FGIDs, although well-designed, Gutiérrez-Castrellon P, Miqdady MIS, Smith P, and affects the immune system in et al. Partially hydrolyzed formula in suggested to be multifactorial such different ways: through a modulatory needed for better understanding of randomized trials are needed to allow non-exclusively breastfed infants: A systematic review and expert consensus. Nutrition as gastrointestinal, psychosocial, and effect of the pro-inflammatory the efficacy mechanism of probiotics to recommend the use of pHF for 2019;57:268–74. doi:10.1016/j.nut.2018.05.018 neurodevelopmental, with increasing signalling via Toll-like receptor 4 in infant colic. treatment in infants with FGIDs.9 9.  Vandenplas Y, Cruchet S, Faure C, Lee H, Di Lorenzo C, Staiano A, et al. Acta Paediatr importance of the role of intestinal (TLR4) and nuclear factor-B (NF-B), 2014;103:689–95. doi: 10.1111/apa.12637 microbiome. Several studies have resulting in decreased mucosal *Due to reclassification of Lactobacillus genus into groups of closely related species, Lactobacillus reuteri is renamed to Limosilactobacillus reuteri (see infographics at page 9)

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