Previous evidence from both mouse models and humans has suggested that manipulation of the gut microbiota could help us understand how to deal with the current global obesity epidemic. However, whether the effects of targeting the gut microbiota are due to improved health status in people with overweight or obesity or the result of changes in their gut microbiota composition or functional diversity has not been yet clarified. The question remains as to whether changes in the gut microbial communities are a cause or a consequence of overweight or obesity, specifically of the unbalanced diet that often accompanies the development of excess weight gain.
A new meta-analysis of 53 randomized controlled trials, led by Prof. Mical Paul from the Ruth and Bruce Rappaport Faculty of Medicine at the Technion Israel Institute of Technology and the Infectious Diseases Institute at Rambam Health Care Campus in Haifa (Israel), has concluded that further and better studies are needed for supporting the use of probiotics, prebiotics, synbiotics, and antibiotics for weight manipulation.
The authors searched the PubMed and Cochrane Library databases for randomized controlled trials (RCTs) on infants (1 month to two years of age), children (2-18 years), and adults (18 years and above) assessing the effects of prebiotics, probiotics, synbiotics, and antibiotics on weight. Weight change from baseline was used as the primary outcome.
23 infant, 17 children, and 13 adult RCTs were identified and included; the analysis included both RCTs and cross-over RCTs if they reported outcomes at the end of the first cross-over period. In infants, 14 trials examined probiotics, 5 prebiotics, and 4 synbiotics. The studies conducted in children included 7 on probiotics, 2 on prebiotics, 1 on synbiotics, and 4 on antibiotics. Finally, of the adult studies, 15 examined probiotics, 1 prebiotics, 0 synbiotics and 1 antibiotics.
The effects differed between infants/children and adults. Probiotic supplements (mostly Lactobacilli) induced minor weight gain in infants and children and minor weight loss in adults. The minor weight gain observed in children was in relation to Lactobacilli probiotic supplements administered for 2-6.5 months. Among infants, consumption of probiotic enriched formulas for 3 weeks-10 months was associated with borderline significant weight gain. In obese adults 2.7 x 1010 colony forming units (cfu)/day of Lactobacilli probiotics for 2-3 months was associated with significant weight loss. The authors found that heterogeneity was substantial in the infant and adult analyses and could not be explained by intervention or patient characteristics.
Prebiotics did not have significant effects on absolute end weight in infants, children or adults.
Intervention studies of synbiotics in infants and children did not reveal significant differences between the intervention and control groups.
Regarding studies evaluating the effects of antibiotics vs. placebo on weight gain, azithromycin administration in children with cystic fibrosis and bronchiectasis resulted in weight gain, without heterogeneity between studies. These data were in agreement with one study in humans that found a small but significant increase in weight with clarithromycin. Although antibiotic administration cannot be recommended yet for weight manipulation, these results suggest they could have advantageous effects on weight gain for those children with pulmonary disease.
Specifically, the authors mentioned in their review that the weight gain in malnourished children associated with antibiotic exposure is not clearly attributable to microbiota changes or to alleviation of infection and inflammation. In this case severe malnutrition may be a confounding factor, as in a recent study involving twins from Malawi and mouse models researchers found that gut dysbiosis caused susceptibility to kwashiorkor, a severe form of undernutrition, and antibiotics may act just by restoring gut microbiota to a healthy state, potentially explaining the weight gain.
Regarding assessment of risk of bias, the authors reported that outcome assessors were unblinded in most studies and there was a high risk of incomplete outcome data (attrition bias). Besides this, less than half of the trials were registered under a public registry and, among studies registered, only about 1/3 reported on their pre-defined primary outcomes (bias related to selective reporting). Altogether, this high risk of bias detected across the studies evaluated makes it difficult to draw clear conclusions.
In conclusion, although several environmental factors including pro-, pre-, syn-, and antibiotics may have a role in weight manipulation in children and adults, further and better studies are needed in order to recommend them in clinical practice.
Dror T, Dickstein Y, Dubourg G, Paul M. Microbiota manipulation for weight change. Microb Pathog. 2017; 106:146-61.