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 (6-18 years, Tanner stage ≥2) with obesity and insulin-resistance on diet were randomized to 2 × 109 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%0.0-0.03) and during OGTT (ISI, 0.654 CI95%-0.11-1.41). 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.

Keywords: Insulin sensitivity; Microbiota; Pediatric obesity; Probiotics.

Conflict of interest statement

Conflict of interests Dr. Prodam reported grants from the Muscular Dystrophy Association, EuroTransBio Program, Cariplo Foundation, Novo Nordisk during the conduct of the study, and personal fees from Eli Lilly (speaker) and Difass International (advisory board) outside the submitted work. Dr. Bellone reported during the conduct of the study personal fees from Difass International (advisory board) outside the submitted work. Dr. Bona reported grants from Cariplo Foundation, Comunità Novarese Foundation, AIFA during the conduct of the study, and personal fees Pfizer, Consumer Healthcare, Guna, and Vox (advisory boards and speaker) outside the submitted work. He also participated in the GQM05, V59-66 (Novartis), MMRV063 (OKAH), V 118_05, and Boostrix 048 (Glaxo SmithKline Biologicals) multicenter studies on vaccines during the conduct of the study. Dr. Aimaretti reported grants from the EuroTransBio Program, MIUR (PRIN grant), and personal fees from Sanofi, Astra Zeneca, and Novo Nordisk (advisory boards) outside the submitted work. Dr. Di Gioia reported an intramural grant from University of Bologna during the conduct of the study. Dr. Vitulo reported grants from MIUR (National Antartic Research Program, PNRA), personal fee from Lavazza S.p.A and ILLY S.p.A companies and CSIRIO (Commonwealth Scientific and Industrial Research Organisation, Australia) outside the submitted work (consultants). He received fee from Probiotical Research SRL for the present project. Marco Pane is employee of Probiotical Research Srl. Angela Amoruso is employee of Probiotical Research Srl.

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