Supplementation with Bifidobacterium breve BR03 and B632 strains improved insulin sensitivity in children and adolescents with obesity in a cross-over, randomized double-blind placebo-controlled trial

Abstract

Background & aims: Variations in gut microbiota might impact metabolism leading to body weight excess. We assessed the impact of a probiotic supplementation in pediatric obesity on weight, metabolic alterations, selected gut microbial groups, and functionality. Methods: Cross-over, double-blind, randomized control trial (BIFI-OBESE trial; NCT03261466). 101 youths (6e18 years, Tanner stage !2) with obesity and insulin-resistance on diet were randomized to 2 Â 10 9 CFU/AFU/day of Bifidobacterium breve BR03 (DSM 16604) and B. breve B632 (DSM 24706) (51) or placebo (50) for 8 weeks with a 4-weeks wash-out period. Results: All subjects (M/F 54/47) completed the first 8 weeks, and 82 (M/F 43/39) the last part without adverse events. Mixed-effects models revealed a carry-over effect on many variables in the entire study, narrowing the analysis to the first 8 weeks before the wash-out periods. All subjects improved metabolic parameters, and decreased weight and Escherichia coli counts. Probiotics improved insulin sensitivity at fasting (QUICKI, 0.013 CI95%0.0e0.03) and during OGTT (ISI, 0.654 CI95%-0.11e1.41). Cytokines, GLP1, and target microbial counts did not vary. Of 25 SCFAs, acetic acid and acetic acid pentyl-ester relative abundance remained stable in the probiotics, while increased in the placebo (p < 0.02). A signature of five butanoic esters identified three clusters, one of them had better glucose responses during probiotics. Conclusion: An 8 weeks treatment with B. breve BR03 and B632 had beneficial effects on insulin sensitivity in youths with obesity. Microbiota functionality could influence metabolic answers to probiotics. Long-term studies to confirm and enrich our findings are justified. Tailored probiotic treatments could be an additional strategy for obesity. Trial registration: NCT03261466.

Maternal gut microbiota Bifidobacterium promotes placental morphogenesis, nutrient transport and fetal growth in mice

“…Previous in vivo studies show different strains of Bifidobacterium (including B. breve ) modulate glucose handling [ 49 ], with this genus consistently associated with potential protection against human metabolic disorders e.g. type 2 diabetes [ 50 , 51 ]. Our observations of reduced maternal gonadal fat mass and maternal liver weight in B. breve -treated dams compared to SPF dams, suggest that Bifidobacterium, or B. breve metabolites, could affect responses of key organs in the mother, and subsequently impact fetal resource allocation.…”

Maternal gut microbiota Bifidobacterium promotes placental morphogenesis, nutrient transport and fetal growth in mice

“…In our case, Igf2P0 was significantly elevated in the BIF group compared to the SPF and GF groups and although in vivo functional assays evaluating the passive and active transport of solutes are required to verify the implications of this effect on fetal nutrient allocation (e.g. performing unidirectional maternal-fetal transfer assays using 51 Cr-EDTA or glucose and amino acid analogues, 3 H-MeG or 14 C-MeAIB [23,61,62]), this result explains, in part, the improvement in fetal weight observed in the BIF group. Moreover, IGFs have been implicated in the regulation of glucose transporters in a variety of organs by utilizing signalling pathways like PI3K/AKT and MAPK [63], and among the different nutrient transporters evaluated, Slc2a1 mRNA levels were significantly elevated in the BIF group compared to GF group.…”

The intestine and the microbiota in maternal glucose homeostasis during pregnancy

“…Gut microbiota exert many of their effects on the host via bacterial components ( Kikuchi et al 2018 , Solito et al 2021 ). The paracellular movement of live bacteria and/or their components through an impaired intestinal barrier has been suggested to contribute to T2DM- and obesity-related insulin resistance; a state referred to as metabolic endotoxemia ( Cani et al 2007 ).…”