Effect of L. reuteri on bowel movements in children aged 6 months to 4 years: A double-blind randomized controlled trial

Camille Jung, Nicolas Kalach, Vanessa Degas, Yasmine Jeridi, Valérie Bertrand, Marc Bellaiche, Camille Jung, Nicolas Kalach, Vanessa Degas, Yasmine Jeridi, Valérie Bertrand, Marc Bellaiche

Abstract

Background: Chronic constipation is common in children and often requires prolonged laxative treatment. Preliminary studies suggest that the probiotic Limosilactobacillus reuteri (L. reuteri) may be useful in treating constipation in children, but these preliminary results need to be replicated. The objective of this study was to assess the efficacy of L. reuteri in infants and young children with chronic functional constipation.

Methods: A prospective double-blind randomized placebo-controlled trial was conducted in 5 pediatric departments in France between June 2017 and June 2021. In all, 49 patients-ages 6 months to 4 years, and suffering from chronic constipation per Rome IV criteria-were randomly allocated to the test and control groups. For 4 weeks, all were orally administered 5 daily drops of the test (L. reuteri DSM 17938 at 108 colony-forming units per day) or control (placebo) treatment, respectively. Participants were clinically assessed at 4 and 8 weeks. Parents were asked to daily record the number of spontaneous bowel movements (SBMs), stool consistency, and the use of any additional laxatives. Informed consent was obtained from parents of all recruited patients, and the study was approved by both an ethics committee and the French National Agency for Medicines and Health Products Safety (ANSM). The study is registered on ClinicalTrials.gov (NCT03030664).

Results: The change in SBMs relative to baseline was greater in the control group at week 4 (control: 0.27 ± 0.5; test: 0.23 ± 0.5; P = 0.01) and in the test group at week 8 (control: 0.26 ± 0.4; test: 0.22 ± 0.5; P = 0.03). At week 4, the groups did not differ in number of responders (≥3 stools per week, with no non-retentive fecal incontinence), use of rescue medication, scoring of pain during defecation (Faces Pain Scale-Revised), or stool consistency (Bristol Stool Form Scale).

Conclusion: This double-blind randomized controlled trial did not confirm the efficacy of L. reuteri for treatment of chronic functional constipation in young children.

Keywords: Limosilactobacillus reuteri; children; functional constipation; infant; randomized controlled trial.

Conflict of interest statement

MB and VD performed lectures for Biogaia. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

© 2022 Jung, Kalach, Degas, Jeridi, Bertrand and Bellaiche.

Figures

Figure 1
Figure 1
Study flow diagram.
Figure 2
Figure 2
Change in number of stools at weeks 4 and 8 relative to baseline.
Figure 3
Figure 3
Change in PedsQL family impact module scores for test and control groups.

References

    1. Tabbers MM, DiLorenzo C, Berger MY, Faure C, Langendam MW, Nurko S, et al. Evaluation and treatment of functional constipation in infants and children: evidence-based recommendations from ESPGHAN and NASPGHAN. J Pediatr Gastroenterol Nutr. (2014) 58:258–74. 10.1097/MPG.0000000000000266
    1. Hyams JS, Di Lorenzo C, Saps M, Shulman RJ, Staiano A, van Tilburg M. Functional disorders: children and adolescents. Gastroenterology. (2016) S0016-5085(16):00181–5. 10.1053/j.gastro.2016.02.015
    1. Benninga MA, Faure C, Hyman PE, St James Roberts I, Schechter NL, Nurko S. Childhood functional gastrointestinal disorders: neonate/toddler. Gastroenterology. (2016) S0016-5085(16):00182–7. 10.1053/j.gastro.2016.02.016
    1. Tabbers MM, Boluyt N, Berger MY, Benninga MA. Constipation in children. BMJ Clin Evid. (2010) 2010:0303.
    1. Ford AC, Sperber AD, Corsetti M, Camilleri M. Irritable bowel syndrome. Lancet. (2020) 396:1675–88. 10.1016/S0140-6736(20)31548-8
    1. Jomehzadeh N, Javaherizadeh H, Amin M, Rashno M, Teimoori A. Quantification of intestinal Lactobacillus Species in children with functional constipation by quantitative real-time PCR. Clin Exp Gastroenterol. (2020) 13:141–50. 10.2147/CEG.S250755
    1. Dempsey E, Corr SC. Lactobacillus spp. for gastrointestinal health: current and future perspectives. Front Immunol. (2022) 13:840245. 10.3389/fimmu.2022.840245
    1. Coccorullo P, Strisciuglio C, Martinelli M, Miele E, Greco L, Staiano A. Lactobacillus reuteri (DSM 17938) in infants with functional chronic constipation: a double-blind, randomized, placebo-controlled study. J Pediatr. (2010) 157:598–602. 10.1016/j.jpeds.2010.04.066
    1. Kubota M, Ito K, Tomimoto K, Kanazaki M, Tsukiyama K, Kubota A, et al. Lactobacillus reuteri DSM 17938 and magnesium oxide in children with functional chronic constipation: a double-blind and randomized clinical trial. Nutrients. (2020) 12:E225. 10.3390/nu12010225
    1. Wegner A, Banaszkiewicz A, Kierkus J, Landowski P, Korlatowicz-Bilar A, Wiecek S, et al. The effectiveness of Lactobacillus reuteri DSM 17938 as an adjunct to macrogol in the treatment of functional constipation in children. A randomized, double-blind, placebo-controlled, multicentre trial. Clin Res Hepatol Gastroenterol. (2018) 42:494–500. 10.1016/j.clinre.2018.03.008
    1. Bouhnik Y, Neut C, Raskine L, Michel C, Riottot M, Andrieux C, et al. Prospective, randomized, parallel-group trial to evaluate the effects of lactulose and polyethylene glycol-4000 on colonic flora in chronic idiopathic constipation. Aliment Pharmacol Ther. (2004) 19:889–99. 10.1111/j.1365-2036.2004.01918.x
    1. Båth K, Roos S, Wall T, Jonsson H. The cell surface of Lactobacillus reuteri ATCC 55730 highlighted by identification of 126 extracellular proteins from the genome sequence. FEMS Microbiol Lett. (2005) 253:75–82. 10.1016/j.femsle.2005.09.042
    1. Jonsson H, Ström E, Roos S. Addition of mucin to the growth medium triggers mucus-binding activity in different strains of Lactobacillus reuteri in vitro. FEMS Microbiol Lett. (2001) 204:19–22. 10.1111/j.1574-6968.2001.tb10855.x
    1. Connolly E, Abrahamsson T, Björkstén B. Safety of D(-)-lactic acid producing bacteria in the human infant. J Pediatr Gastroenterol Nutr. (2005) 41:489–92. 10.1097/01.mpg.0000176179.81638.45
    1. Benninga M, Candy DCA, Catto-Smith AG, Clayden G, Loening-Baucke V, Di Lorenzo C, et al. The Paris consensus on childhood constipation terminology (PACCT) group. J Pediatr Gastroenterol Nutr. (2005) 40:273–5. 10.1097/01.mpg.0000158071.24327.88
    1. Hicks CL, von Baeyer CL, Spafford PA, van Korlaar I, Goodenough B. The faces pain scale-revised: toward a common metric in pediatric pain measurement. Pain. (2001) 93:173–83. 10.1016/S0304-3959(01)00314-1
    1. Bieri D, Reeve RA, Champion DG, Addicoat L, Ziegler JB. The faces pain scale for the self-assessment of the severity of pain experienced by children: development, initial validation, and preliminary investigation for ratio scale properties. Pain. (1990) 41:139–50. 10.1016/0304-3959(90)90018-9
    1. Ojetti V, Ianiro G, Tortora A, D’Angelo G, Di Rienzo TA, Bibbò S, et al. The effect of Lactobacillus reuteri supplementation in adults with chronic functional constipation: a randomized, double-blind, placebo-controlled trial. J Gastrointestin Liver Dis. (2014) 23:387–91. 10.15403/jgld.2014.1121.234.elr
    1. García Contreras AA, Vásquez Garibay EM, Sánchez Ramírez CA, Fafutis Morris M, Delgado Rizo V. Lactobacillus reuteri DSM 17938 and Agave inulin in children with cerebral palsy and chronic constipation: a double-blind randomized placebo controlled clinical trial. Nutrients. (2020) 12:2971. 10.3390/nu12102971
    1. Indrio F, Di Mauro A, Riezzo G, Civardi E, Intini C, Corvaglia L, et al. Prophylactic use of a probiotic in the prevention of colic, regurgitation, and functional constipation: a randomized clinical trial. JAMA Pediatr. (2014) 168:228–33. 10.1001/jamapediatrics.2013.4367

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren