The effect of intestinal flora intervention on bone development in children: A systematic review and meta-analysis

Background The intestinal flora is involved in the bone development of children through a variety of mechanisms, but it remains unclear whether intervention of the intestinal flora can enhance children's bone development. Methods Six databases (PubMed, Web of Science, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health, and China National Knowledge Infrastructure) were searched for all English and Chinese studies published up to August 2021. Stata version 16.0 (StataCorp, College Station, TX, USA) was used. Bone mass density and biochemical markers related to bone metabolism were reported as the primary outcome, and the secondary outcomes were anthropometric parameters such as height, height Z score for age, and height velocity. Intergroup differences were determined by standardized mean differences (SMDs) and 95% confidence intervals (CIs). Results A total of 3245 participants from 20 RCTs and 370 participants from 8 crossover trials were included in the study. Significant differences were found in bone mineral density (SMD 0.47; 95% CI, 0.28 to 0.66; p < 0.001; I2 = 0.00%) and total serum calcium (SMD 1.07; 95% CI, 0.39 to 1.74; p < 0.001; I2 = 61.9%), as well as in height Z score for age (SMD = 0.11; 95% CI, 0.00 to 0.22; P = 0.044; I2 = 0%). The overall quality of evidence ranged from moderate to very low. Conclusions This systematic review and meta-analysis suggested that intestinal flora intervention was an effective method of improving bone mineral density, serum calcium, and height in infants, children, and adolescents. Future studies with a larger sample size and longer intervention period are needed.The protocol of this systematic review was registered in PROSPERO and the registered number was CRD42021282606.