Identifying the factors influencing outcome in probiotic studies in overweight and obese patients: host or microbiome?

We read with interest Rodriguez and colleagues’ study, using microbiota transfer from obese stool donors into inulin-treated hum-ob mice, to define a gut microbiome signature predicting response to prebiotic.1 However, the impact of other microbiome-based interventions (and particularly probiotics) on weight loss in humans is highly-variable between individuals.2 We were interested as to whether baseline gut microbiota, or aspects of host physiology, may predict weight loss during probiotic studies. In our recent double-blind study (ISRCTN12562026), overweight/obese adults were randomised to either 6 months of Lab4P probiotic (containing lactobacilli and bifidobacteria) or placebo.3 A higher proportion of participants receiving probiotic lost weight compared with those receiving placebo, and the extent of weight loss in the probiotic arm was greater than the placebo group.3 We subsequently performed metataxonome and metabonome analysis on stool samples from study participants (using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry bile acid profiling, respectively, applying established protocols4 5). We observed no difference in stool microbiota alpha-diversity at baseline between participants losing weight during the study versus those who did not (figure 1A); furthermore, no differences were observed in microbiota composition between groups at any taxonomic level. Conversely, on stool bile acid profiling, …