مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Lactobacillus reuteri DSM 17938 interventions for reduction of crying time in infantile colic and associated fecal microbiome changes: a strain-level systematic review
Lactobacillus reuteri DSM 17938 interventions for reduction of crying time in infantile colic and associated fecal microbiome changes: a strain-level systematic review
Alireza Pourrahim,1,*Omid Raiesi,2Mohammad Mahdi Pourrahim,3Khadijeh Najafi Ghobadi,4
1. Student Research Committee, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran. 2. Department of Parasitology, School of Allied Medical Sciences, Ilam University of Medical Sciences, Ilam, Iran. 3. Student Research Committee, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran. 4. Department of Biostatistics, Faculty of Health, Ilam University of Medical Sciences, Ilam, Iran.
Introduction: Infantile colic is common, distressing, and of uncertain etiology; perturbations of the gut microbiome have been implicated. Lactobacillus reuteri DSM 17938 has been proposed as a targeted probiotic therapy; randomized trials and mechanistic studies report conflicting results. We performed a strain-level systematic review synthesizing randomized evidence for clinical efficacy (crying time, responder rates) and human fecal microbiome findings.
Methods: We conducted a systematic search across several databases including PubMed/MEDLINE, Embase, Scopus, Web of Science and ClinicalTrials.gov up to May 2025, adhering to PRISMA guidelines. Search terms combined: (“Lactobacillus reuteri”) AND (“infantile colic”) AND (“microbiome”) and their MeSH/Emtree equivalents. Eligibility: randomized controlled trials (RCTs) of L. reuteri DSM 17938 in infants with colic (Wessel/Rome criteria) assessing crying/fussing time or responder rates; mechanistic human studies reporting pre/post fecal microbiome sequencing were also included. Two reviewers independently screened titles/abstracts and full texts, extracted data (population, feeding status, dose/duration, crying time, ≥50% responder rates, microbiome metrics, adverse events) and assessed risk of bias (RoB-2 for RCTs). Because outcomes and reporting formats varied, we synthesized results narratively and calculated simple descriptive summaries; meta-analysis was not performed due to clinical and metric heterogeneity.
Results: Six trials/studies (all randomized human studies or randomized subsets; total randomized/analysed infants ≈434) met inclusion: Savino et al. 2010 (n≈50), Szajewska et al. 2013 (n=80), Chau et al. 2015 (n=52), Sung et al. 2014 (n=167), Fatheree et al. 2017 (phase-1 safety, n=20), and Nation et al. 2017 (subset analysis, n=65). Findings were mixed. Three trials (Savino et al., Szajewska et al., and Chau et al.) reported statistically significant clinical benefit of L. reuteri DSM 17938 versus placebo: higher proportions achieving ≥50% reduction in crying and substantially lower median/mean daily crying time at day 21 (examples: Savino median crying 35 vs 90 min/day at day 21; Chau cumulative crying over 21 days 29 h vs 37 h). Two trials (Sung et al., Fathereeet al.) found no clinical benefit (Sung: mean crying/fuss time higher in probiotic arm at 1 month; Fatheree: small safety trial with high placebo response). Nation et al. found overall crying reductions but no consistent microbiome or inflammation differences by colonization status; L. reuteri density paradoxically correlated with increased crying in that subset. Microbiome results were heterogeneous: several studies reported increases in fecal lactobacilli and reductions in certain Proteobacteria (e.g., Escherichia coli, Klebsiella) in responders, but sequencing platforms, endpoints and timing varied. Adverse events were rare; no serious probiotic-attributable events reported in these trials. Risk of bias ranged from low (double-blind RCTs) to some concerns (small sample/safety trials, incomplete outcome reporting).
Conclusion: Evidence for L. reuteri DSM 17938 in infantile colic is conflicting: several small-to-moderate RCTs report clinically meaningful reductions in crying, particularly in predominantly breastfed cohorts, while larger pragmatic/community samples show no benefit. Microbiome data suggest treatment-associated compositional shifts in some responders but are inconsistent. Heterogeneity in feeding status, trial populations, outcome metrics and microbiome methods limits pooled inference. Larger, adequately powered, strain-explicit RCTs stratified by feeding mode with standardized crying and sequencing endpoints are needed to clarify efficacy, mechanism and target subgroups.