Probiotics Infant Colic: Pivotal Findings in 2 Subgroups
L. reuteri evidence, formula-fed gaps, and what to tell families seeking a solution
One-Minute Takeaway on Probiotics Infant Colic
Key points at a glance:
- Probiotics infant colic evidence is dominated by L. reuteri DSM 17938, with the most consistent benefit observed in exclusively breastfed infants.
- Pooled individual patient data show a mean reduction in crying time of approximately 25 minutes per day among breastfed infants, with no demonstrable effect in formula-fed cohorts.
- No probiotic strain other than L. reuteri DSM 17938 has accumulated multi-trial evidence for colic treatment.
- Safety across trials is reassuring, but parental expectations frequently exceed what the current evidence supports.
Why Probiotics Infant Colic Captured Parental Attention
Infant colic affects an estimated 5–25% of otherwise healthy infants during the first three months of life. The condition is benign and self-limited, yet the experience of inconsolable crying drives substantial family distress, urgent care visits, and parental fatigue. Few situations push families to seek interventions as intensely as colic.
The probiotics infant colic conversation has expanded rapidly over the past decade. Direct-to-consumer marketing, parenting forums, and pharmacy shelf placement have positioned L. reuteri drops as a first-line option in many families’ minds. This consumer momentum has outpaced the controlled evidence, particularly for formula-fed infants — the group most likely to be offered probiotic drops in retail settings.
For pediatric clinicians, the probiotics infant colic question is now less about whether a product exists and more about how to frame realistic expectations. The discussion turns on three issues: which strain has data, which infants benefit, and how much improvement is plausible. The evidence answers some of these clearly and leaves others open.
Why this matters in clinic
Evidence Reviewed for Probiotics Infant Colic
The probiotics infant colic literature centers on a small number of randomized trials and one individual patient data meta-analysis. Most trials evaluated L. reuteri DSM 17938 at a daily dose of 1 × 10⁸ CFU. The evidence base spans Italy, Australia, Canada, the United States, and Ukraine, with mixed populations and clear methodological differences.
The comparative table below summarises the most influential trials. The studies differ by feeding mode of participants, primary outcome definition, dose, and follow-up duration. These differences explain much of the apparent inconsistency in headline findings across trials.
| Study | Design | n | Population | Intervention | Primary Finding |
|---|---|---|---|---|---|
| Savino 2007 | Open-label RCT | 90 | Breastfed | L. reuteri ATCC 55730 vs simethicone | Favored probiotic at day 28 |
| Savino 2010 | Double-blind RCT | 50 | Breastfed | L. reuteri DSM 17938 vs placebo | Favored probiotic at day 21 |
| Chau 2015 | Double-blind RCT | 52 | Breastfed | L. reuteri DSM 17938 vs placebo | Favored probiotic at day 21 |
| Mi 2015 | Single-blind RCT | 42 | Breastfed | L. reuteri DSM 17938 vs placebo | Favored probiotic; reduced maternal depression scores |
| Sung 2014 (BIS) | Double-blind RCT | 167 | Mixed (predominantly formula-fed) | L. reuteri DSM 17938 vs placebo | No significant overall reduction in crying |
| Fatheree 2017 | Double-blind RCT | 20 | Exclusively formula-fed | L. reuteri DSM 17938 vs placebo | No significant difference |
| Sung 2018 IPDMA | Individual patient data meta-analysis | 345 | Pooled (stratified by feeding) | L. reuteri DSM 17938 | Benefit in breastfed; not formula-fed |
| Indrio 2014 | Multicenter prevention RCT | 589 | Newborn prevention cohort | L. reuteri DSM 17938 vs placebo | Less crying, regurgitation, constipation |
When the trials are read together rather than individually, a coherent picture emerges. The probiotics infant colic evidence is not contradictory — the apparent disagreement between positive trials and the Sung 2014 BIS trial is largely explained by feeding mode of enrolled infants. The 2018 IPDMA made this explicit by stratifying outcomes.
Probiotics Infant Colic — Key Findings by Theme
L. reuteri DSM 17938 Is the Only Strain With Replicated Trial Evidence
Across the probiotics infant colic literature, L. reuteri DSM 17938 is the only strain that has accumulated more than one well-conducted randomized trial demonstrating a treatment effect. Other strains — L. rhamnosus GG, multi-strain Lactobacillus and Bifidobacterium blends, and various commercial formulations — have appeared in small studies or none at all.
The evidence for each non-reuteri strain is too thin to support claims of effectiveness. This is a clinically important distinction because the commercial market includes many products marketed for colic that contain strains never tested in colic-specific trials.
Effect Sizes Diverge Sharply Between Breastfed and Formula-Fed Infants
The Sung 2018 individual patient data meta-analysis pooled four randomized trials and stratified outcomes by feeding mode. In breastfed infants, L. reuteri DSM 17938 reduced crying duration by a mean of approximately 25 minutes per day at day 21. In formula-fed infants, the point estimate showed no meaningful effect and confidence intervals crossed zero.
The Sung 2014 BIS trial, which enrolled a predominantly formula-fed Australian population, found no significant overall benefit on crying time. The Fatheree 2017 trial, which enrolled exclusively formula-fed infants, also failed to demonstrate a treatment effect. These findings together define the central tension of the probiotics infant colic conversation.
Mechanistic Hypotheses Remain Unresolved
Researchers have proposed that L. reuteri may alter gut motility, reduce visceral pain signaling, modulate immune function in the infant gut, or shift intestinal microbiota composition. None of these mechanisms has been confirmed as the primary driver of the observed clinical effect.
The mechanistic uncertainty parallels the population uncertainty. Clinicians know L. reuteri can help breastfed infants without fully understanding why. The leading hypothesis links human milk oligosaccharides to probiotic engraftment, but this remains exploratory.
Prevention Is a Separate Question From Treatment
The Indrio 2014 Italian multicenter prevention trial randomized nearly 600 newborns to L. reuteri DSM 17938 or placebo for three months. The trial reported reductions in mean daily crying time, regurgitation episodes, and constipation in the probiotic arm. The prevention question — whether starting probiotics in the first weeks of life reduces colic incidence — is distinct from the treatment question.
The evidence base for prevention remains less mature than for treatment, and a 2024 Cochrane review on probiotics for the prevention of infant gastrointestinal symptoms emphasized continued uncertainty. Prevention should not be conflated with treatment when counseling families.
Most trials in the probiotics infant colic literature used the modified Wessel criteria: crying for more than three hours per day, on more than three days per week, for at least three weeks, in an otherwise well infant. The Rome IV functional criteria, published in 2016, define infant colic somewhat differently and have been applied inconsistently in more recent work.
This definitional drift complicates direct comparison across studies and contributes to between-trial heterogeneity in apparent effect size. When evaluating a new trial, the population definition deserves close attention.
Several hypotheses attempt to explain why L. reuteri DSM 17938 appears effective in breastfed but not formula-fed infants:
- Human milk delivers specific oligosaccharides that shape the gut microbiota in a way standard formula does not, potentially priming the gut for probiotic colonization
- Formula-fed infants already have a substantially different baseline microbiota, which may render an added probiotic strain less able to integrate
- Maternal microbiota transfer through breastfeeding may interact synergistically with supplemental probiotic strains
None of these hypotheses has been confirmed in dedicated mechanistic trials.
L. rhamnosus GG was evaluated in a small Finnish trial without demonstrable benefit on crying time. Bifidobacterium-containing multi-strain products appear in marketed colic blends but lack dedicated randomized trials for the colic indication.
The commercial probiotic supplement market for colic includes strains never tested in colic-specific RCTs. Clinicians should not assume cross-strain equivalence: the evidence for L. reuteri DSM 17938 does not generalize to other Lactobacillus species or to multi-strain formulations. Each strain is a distinct biological entity and must be evaluated on its own evidence base.
Across positive trials, the standard L. reuteri DSM 17938 dose has been 1 × 10⁸ CFU once daily, typically delivered as five oil-suspended drops. Treatment duration has ranged from 21 to 28 days. No trial has compared shorter versus longer regimens, and no trial has compared once-daily versus split dosing.
Storage conditions matter for live-organism products: refrigeration is recommended for many commercial formulations to preserve potency. Counsel families to check expiration dates and storage instructions on the specific product they purchase.
Quality and Consistency of Probiotics Infant Colic Evidence
The probiotics infant colic evidence base is more heterogeneous than headline marketing claims suggest. Trials differ in feeding population, primary outcome definition, dose, and follow-up duration. The colored-dot summary below rates evidence consistency across the sub-questions clinicians actually ask in clinic.
Counseling Tip
Knowledge Gaps in the Probiotics Infant Colic Literature
Despite a decade of randomized trials, several pivotal clinical questions about probiotics infant colic remain unanswered. The gaps below name specific evidence shortfalls rather than calling broadly for “more research.”
What the Evidence Does NOT Show
- No adequately powered trial in exclusively formula-fed infants has demonstrated benefit on daily crying time.
- No head-to-head randomized trial has compared L. reuteri DSM 17938 with other commercially marketed probiotic strains for colic.
- Long-term follow-up beyond 28 days is sparse; the durability of crying reduction after treatment ends has not been characterized.
- The mechanistic basis for the apparent breastfed-only effect has not been confirmed in human trials.
- Definitions of “colic” differ across trials (modified Wessel vs. Rome IV functional criteria), introducing comparability problems.
- No randomized evidence informs whether probiotics alter the natural history of colic versus shifting the timing of crying within the day.
Naming these gaps openly during counseling builds trust with families. It also positions probiotics infant colic recommendations as evidence-based rather than reactive to marketing pressure. Where evidence is absent, saying so is the appropriate clinical response.
Practical Implications for Pediatric Practice
The practical implications below frame what current evidence supports rather than what individual clinicians should prescribe. Each consideration reflects the consistency and direction of the underlying trial data.
Pediatric clinicians can also use the visit to ask about the family’s broader stress and support resources. The probiotics infant colic conversation is often a proxy for an exhausted parent seeking validation, and the visit may be more useful for what surrounds the recommendation than for the recommendation itself.
Evidence Grade and Bottom Line
Evidence Grade: Moderate for L. reuteri DSM 17938 in exclusively or predominantly breastfed infants meeting modified Wessel colic criteria. Insufficient for formula-fed infants and for non-reuteri probiotic strains.
The grading reflects concordant findings across multiple randomized trials and a stratified individual patient data meta-analysis in breastfed populations, balanced against the absence of demonstrable effect in formula-fed populations and the lack of adequate evidence for any other probiotic strain.
Bottom Line
- L. reuteri DSM 17938 reduces crying time by approximately 25 minutes per day in breastfed infants with colic, supported by multiple randomized trials and an individual patient data meta-analysis.
- The same evidence base does not extend to formula-fed infants, where pooled data show no measurable effect on daily crying duration.
- No other probiotic strain has accumulated comparable evidence for colic treatment, and commercial products vary widely in strain composition.
- Probiotics are safe in healthy term infants, but parental expectations frequently exceed what the literature supports.
- Anticipatory guidance, soothing technique counseling, and family support remain the foundation of colic management, regardless of whether probiotics are used.
Article Information and References
For Educational Purposes Only. This is an original evidence synthesis informed by the studies listed below. It does not replace clinical judgement. Drug dosages should be verified against current prescribing information.
References
- Sung V, D’Amico F, Cabana MD, et al. Lactobacillus reuteri to Treat Infant Colic: A Meta-analysis. Pediatrics. 2018;141(1):e20171811. DOI: 10.1542/peds.2017-1811
- Sung V, Hiscock H, Tang ML, et al. Treating infant colic with the probiotic Lactobacillus reuteri: double blind, placebo controlled randomised trial. BMJ. 2014;348:g2107. DOI: 10.1136/bmj.g2107
- Chau K, Lau E, Greenberg S, et al. Probiotics for infantile colic: a randomized, double-blind, placebo-controlled trial investigating Lactobacillus reuteri DSM 17938. J Pediatr. 2015;166(1):74-78. DOI: 10.1016/j.jpeds.2014.09.020
- Savino F, Pelle E, Palumeri E, Oggero R, Miniero R. Lactobacillus reuteri (American Type Culture Collection Strain 55730) versus simethicone in the treatment of infantile colic: a prospective randomized study. Pediatrics. 2007;119(1):e124-e130. DOI: 10.1542/peds.2006-1222
- Savino F, Cordisco L, Tarasco V, et al. Lactobacillus reuteri DSM 17938 in infantile colic: a randomized, double-blind, placebo-controlled trial. Pediatrics. 2010;126(3):e526-e533. DOI: 10.1542/peds.2010-0433
- Mi GL, Zhao L, Qiao DD, Kang WQ, Tang MQ, Xu JK. Effectiveness of Lactobacillus reuteri in infantile colic and colicky induced maternal depression: a prospective single blind randomized trial. Antonie Van Leeuwenhoek. 2015;107(6):1547-1553. DOI: 10.1007/s10482-015-0448-9
- Fatheree NY, Liu Y, Taylor CM, et al. Lactobacillus reuteri for Infants with Colic: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial. J Pediatr. 2017;191:170-178.e2. DOI: 10.1016/j.jpeds.2017.07.036
- Indrio F, Di Mauro A, Riezzo G, et al. Prophylactic use of a probiotic in the prevention of colic, regurgitation, and functional constipation: a randomized clinical trial. JAMA Pediatr. 2014;168(3):228-233. DOI: 10.1001/jamapediatrics.2013.4367
- Schreck Bird A, Gregory PJ, Jalloh MA, Risoldi Cochrane Z, Hein DJ. Probiotics for the Treatment of Infantile Colic: A Systematic Review. J Pharm Pract. 2017;30(3):366-374. DOI: 10.1177/0897190016634516
- Skonieczna-Żydecka K, Janda K, Kaczmarczyk M, Marlicz W, Łoniewski I, Łoniewska B. The Effect of Probiotics on Symptoms, Gut Microbiota and Inflammatory Markers in Infantile Colic: A Systematic Review, Meta-Analysis and Meta-Regression of Randomized Controlled Trials. J Clin Med. 2018;7(9):261. DOI: 10.3390/jcm7090261
- Pärtty A, Lehtonen L, Kalliomäki M, Salminen S, Isolauri E. Probiotic Lactobacillus rhamnosus GG therapy and microbiological programming in infantile colic: a randomized, controlled trial. Pediatr Res. 2015;78(4):470-475. DOI: 10.1038/pr.2015.127
- Gerasimov S, Gantzel J, Dementieva N, et al. Role of Lactobacillus rhamnosus (FloraActive) 19070-2 and Lactobacillus reuteri (FloraActive) 12246 in Infant Colic: A Randomized Dietary Study. Nutrients. 2018;10(12):1975. DOI: 10.3390/nu10121975