The original randomized, double-blind, placebo-controlled trial, recruited 468 infants born at neonatal units in Italy with early FGID symptoms (e.g., colic, regurgitation, constipation), between 2010 and 2012 and assigned them to receive either L. reuteri DSM 17938 (BioGaia AB, Sweden) or placebo during the first three months of life.
The latest study followed-up 200 of the participants who completed assessments at age ten with the primary outcome being the presence of functional abdominal pain (FAP).
Findings published in the journal Nutrients show FAP was diagnosed in 13 of 99 (13.1%) children in the probiotic group and 81 of 101 (80.2%) children in the placebo group, corresponding to an absolute risk reduction of 67.1%, with the strong association remaining after adjustment for baseline covariates.
“If a short course of a targeted probiotic can influence long-term risk of a chronic condition such as FAP, the implications for quality of life and healthcare utilization could be substantial,” the report said.
However, the Italian researchers warned that caution should be taken in reading these results given the limited data on diet, stress, BMI, infections, psychosocial factors, and the potential for attrition bias.
The absence of longitudinal data on these variables limits the ability to disentangle their individual and combined contributions, raising the possibility that cumulative environmental influences over time may partially account for the observed association rather than the early intervention alone.
“Further long-term trials integrating clinical outcomes with microbiome, immune, and neurodevelopmental measures are needed to clarify causal pathways and identify subgroups most likely to benefit,” the report stated.
Despite the noted limitations, the authors said the data add to a growing body of evidence to suggest selected probiotic strains, when administered during specific developmental windows, may have disease-modifying potential.
FAP through childhood
According to Rome IV criteria, FAP is defined as abdominal pain occurring at least four times per month over a minimum period of two months, not exclusively related to physiological events such as eating or menstruation, and not fulfilling criteria for other functional gastrointestinal disorders, including irritable bowel syndrome, functional dyspepsia, or abdominal migraine.
In the follow-up study, all participants underwent a standardized clinical evaluation performed by an experienced pediatric gastroenterologist who remained blinded to the original treatment allocation. Diagnoses were made according to the updated Rome IV criteria for pediatric functional gastrointestinal disorders, ensuring consistency with internationally recognized definitions
Microbial programming
The researchers noted the persistence of the association a decade later suggests mechanisms beyond temporary symptom relief, potentially involving developmental processes affecting the gut, immune system, and enteric nervous system.
Experimental evidence indicates that Lactobacillus reuteri DSM 17938 may modulate host physiology by influencing inflammatory signaling, enhancing mucosal barrier function, and interacting with vagal afferent pathways involved in pain modulation.
Early exposure to such signals may contribute to long-term regulation of gut–brain communication and reduced susceptibility to visceral hypersensitivity, a key feature of functional abdominal pain, the report noted.
What’s more, early microbiota modulation may also affect barrier integrity, low-grade inflammation, and microbial metabolite production, supporting the hypothesis that early microbial interventions can influence long-term gut–brain axis function.
“The concept of microbial programming provides a useful framework, proposing that early microbial exposures influence immune tolerance, stress responsiveness, and sensory processing, with effects that persist into later life,” the authors wrote.
Source: Nutrients, https://doi.org/10.3390/nu18040687 “Long-Term Efficacy of Limosilactobacillus Reuteri DSM17938 in the Prevention of Functional Abdominal Pain Disorders”, Authors: Indrio F., Di Mauro, A., et al
