BH received personal fees from NIHR, the Medical Research Council, and the User Involvement Shared Learning Regorafenib Group. DB, LD, CG. JP and PW have nothing to

disclose. Ethics approval: University of Liverpool Institutional Ethics Board. Provenance and peer review: Not commissioned; externally peer reviewed. Data sharing statement: No additional data are available.
Infant colic, or excessive crying of unknown cause, is a common, burdensome condition affecting up to 20% of infants less than 3 months old.1 Although colic self-resolves beyond the first 3 months of life, it is associated with potentially significant adverse effects, such as maternal depression,2 3 child abuse,4 5 and early cessation of breast feeding.6 There is also some evidence of long-term adverse outcomes, such as behaviour and sleep problems.7 8 The aetiology of infant colic remains unresolved, and effective treatment options are limited.9–11 Recent research has focused on the role of gut microbiota in the pathophysiological pathway to infant colic, with numerous studies revealing differences in gut microbiota between infants with and without colic.12–21 At the same time, a

handful of studies have examined the role of probiotics—live microorganisms believed to confer a health benefit—in the management of infant colic. One study of Lactobacillus reuteri ATCC 5573022 and two studies of L. reuteri DSM 1793823 24 in breastfed infants with colic were effective, but a subsequent study of both breastfed and formula-fed infants with colic indicated L. reuteri DSM 17938 to be ineffective.25 Two other studies using different mixtures of probiotic strains were also ineffective in managing colic.14 26 The reasons for such conflicting evidence are unclear, and there is a need to explore the reasons behind such controversial results, particularly with increasing probiotic marketing, variety of strains used, and addition of probiotics to infant formulae. Currently, there are some ongoing trials examining the role of probiotics in managing and preventing infant colic, using similar

designs, participants, interventions, comparators and Batimastat outcome measures.27 While individual trials can provide important data, and meta-analyses of randomised controlled trials can give important conclusions, there can be problems with interpreting such conclusions. Ultimately, such meta-analyses often do not overcome limitations and biases of individual trials by generating a single best estimate through pooling of treatment effect estimates.28 In contrast, combining raw data from individual trials via an individual participant data meta-analysis (IPDMA) can yield more reliable estimates of treatment effects with universal applicability.28–32 This is particularly important when there is significant chance that particular strains of probiotics may work for particular subgroups of infants with colic, an effect that cannot be detected by individual studies with limited sample sizes.