Gut microbiome-based interventions for the management of obesity in children and adolescents aged up to 19 years.

The epidemic of overweight and obesity affects more than 390 million children and adolescents aged 5 to 19 years and 37 million children under five years of age. Overweight and obesity are associated with both short- and long-term consequences, including chronic inflammation, metabolic diseases, as well as alterations in the gut microbiome composition. Gut microbiome-based approaches may impact microbiome-related metrics such as diversity or the abundance of intestinal bacteria, which may be linked to obesity-related outcomes. However, evidence regarding the effect of gut microbiome-based interventions for the management of obesity is limited. To assess the effects of gut microbiome-based interventions in the management of overweight or obesity in children and adolescents in all their diversity aged 0 to 19 years. We searched CENTRAL, MEDLINE, CINAHL, Web of Science Core Collection, BIOSIS Previews, Global Index Medicus (all regions), IBECS, SciELO, PAHO, PAHO IRIS, WHO IRIS, WHOLIS, Bibliomap, TRoPHI as well as ICTRP Search Portal and ClinicalTrials.gov. The date of the last search for all databases was 24 January 2025. We did not apply any language restrictions. We included randomised controlled trials that evaluated gut microbiome-based interventions [i.e. prebiotics, probiotics, synbiotics, short-chain fatty acids (SCFAs), and faecal microbiota transplantation (FMT)] compared to standard-of-care, placebo, or control interventions in children and adolescents aged 0 to 19 years with overweight or obesity. Two review authors independently screened titles and abstracts and full texts, extracted data, and assessed the risk of bias using the Cochrane Risk of Bias 2 tool and certainty of the evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE), a framework for assessing the certainty of evidence and making recommendations in systematic reviews. Random-effects meta-analyses were performed unless only one study per outcome was available, for which fixed-effect analyses were performed. We found 17 studies (838 participants) from various countries, evaluating the effects of prebiotics, probiotics, synbiotics, SCFAs, and FMT on body mass index (BMI), body weight, waist circumference, total body fat percentage (%TBF), systolic and diastolic blood pressure, and adverse events. Of the 17 studies included, five studies were in adolescents aged 10 to 19 years, and 12 studies were in children and adolescents spanning both age groups, 0 to 19 years. Upon contacting authors for data grouped by age of the participants, no studies provided separate outcomes data for children and adolescents. The included studies were funded by either academic funding sources or grants from the public and private sectors. Additionally, 15 studies were classified as currently being conducted ('ongoing'). The certainty of evidence throughout was very low. In adolescents 10 to 19 years of age, probiotics compared to placebo or no intervention may have little to no effect on BMI, body weight, waist circumference, %TBF, blood pressure, and adverse events. Similarly, FMT compared to placebo may have little to no effect on waist circumference, %TBF, blood pressure, and adverse events in this age group. According to one study with 41 participants and in children and adolescents 0 to 19 years of age, intervention with prebiotics compared to placebo may result in a small reduction in BMI (mean difference = -0.70, 95% CI = -1.25 to -0.15) and body weight (mean difference = -1.5, 95% CI = -2.61 to -0.39). Prebiotics compared to placebo may have little to no effect on waist circumference, %TBF, systolic blood pressure, and adverse events. No data were available on the effect of prebiotics on diastolic blood pressure. Probiotics compared to placebo may have little to no effect on BMI, body weight, waist circumference, %TBF, blood pressure, and adverse events in children and adolescents (0 to 19 years). Synbiotics compared to placebo may result in a reduction in systolic blood pressure (mean difference = -40.00, 95% CI = -50.63 to -29.37) in children and adolescents (0 to 19 years); according to one study with 56 participants. The evidence is very uncertain about the effects of synbiotics compared to a placebo on BMI, body weight, waist circumference, blood pressure, and adverse events. No data were available on the effect of synbiotics compared to placebo on %TBF. Synbiotics, compared to probiotics, may have little to no effect on waist circumference, %TBF, and adverse events. No data were available on the effect of synbiotics compared to probiotics on BMI, body weight, and blood pressure. According to one study with 48 participants and very low-certainty of evidence, SCFAs compared to placebo may result in a reduction in waist circumference (mean difference = -5.08, 95% CI = -7.40 to -2.76) and BMI (mean difference = -2.26, 95% CI = -3.24 to -1.28) in children and adolescents (0-19 years). SCFAs compared to placebo may have little to no effect on adverse events. No data were available on the effect of SCFAs on body weight, %TBF, and blood pressure. Adverse events, i.e. abdominal cramps, abdominal discomfort, abdominal pain, diarrhoea, vomiting, and migraine, were reported in the prebiotics group but with very low incidence. Additionally, adverse events such as nausea and headache were reported in the SCFAs group, but with low incidence. In adolescents aged 10 to 19 years, gut microbiome-based interventions may result in little to no difference in obesity-related outcomes. In children and adolescents aged 0 to 19 years, prebiotics may result in a small reduction in BMI and body weight; synbiotics may result in a reduction in systolic blood pressure, and SCFAs may result in a reduction in BMI and waist circumference, albeit the certainty of evidence was very low. The evidence was of very low certainty due to few studies per comparison, small sample sizes, short intervention durations, and insufficient reporting of adverse events. More rigorous research examining different types of gut microbiome-based interventions for the management of obesity is required in children and adolescents, both in clinical and community settings. Future trials should also report methods related to randomisation, blinding, and compliance, as well as include prespecified analysis plans.