Impact of Body Mass Index (BMI) on the Effect of a Lactobacillus Rhamnosus GG (LGG)/Bifidobacterium Animalis Subspecies Lactis BB-12 (BB-12) Combination on Gut Microbiota (P20-023-19)

This exploratory study builds upon an earlier study of probiotic supplementation¹ to assess the effects of a probiotic combination (P) of LGG and BB-12 on human gut microbiota composition and function, and to uncover an association with BMI. Healthy subjects ingested P for 21 days (n = 18, P group) or did not (n = 7, C group). Fecal samples obtained at baseline (D_0) and after 21 days of supplementation (D_21) underwent 16S ribosomal RNA gene and shotgun metagenomics sequencing to characterize the bacterial and archaeal communities to the genus/species level and identify functional community genes. Following P ingestion, no global differences in microbiota community structure or relative gene abundance were detected. In targeted analyses, the abundances of LGG and BB-12 in the P group at D_21 increased in a statistically significant manner as the BMI decreased (Spearman correlation, P = 0.04 and P = 0.01, respectively). The relative abundance of LGG but not BB-12 appeared increased in P subjects at D_21 with BMI < 25 compared to BMI > 25 (P = 0.09). P group subjects with BMI < 25 demonstrated trends toward or statistically significant increases in the relative abundances of 5 genes involved with flagellar structure (KEGG orthologs K02422, P = 0.04; K03406, P = 0.06; K02407, P = 0.08; K02397, P = 0.08; K02396, P = 0.09) at D_21 compared to those with BMI > 25. No such differences were observed for the C group nor were there differences in relative gene abundance at D_0 in the P group with BMI < 25 vs BMI > 25. We observed no global changes in the fecal microbial community structure or function with P ingestion in this sample of healthy persons. However, we did observe patterns suggestive of a potential link between BMI and the response of the gut microbiota to P. Although our results are based on a small number of subjects, they are in line with previous findings related to LGG supplementation and the expression of flagellar genes². We agree with other recent reports that future studies would benefit from a detailed examination of the transcriptome, proteome and/or metabolome to better understand the potential impact of probiotics on the gut microbiota, and the mechanism of the effect of BMI. Pfizer Inc.