The Effects of Bifidobacterium Probiotic Supplementation on Blood Glucose: A Systematic Review and Meta-Analysis of Animal Models and Clinical Evidence

Abstract

Probiotic supplementation is a potential therapeutic for metabolic diseases, including obesity, metabolic syndrome (MetS), and type 2 diabetes (T2D), but most studies deliver multiple species of bacteria in addition to prebiotics or oral pharmaceuticals. This may contribute to conflicting evidence in existing meta-analyses of probiotics in these populations and warrants a systematic review of the literature to assess the contribution of a single probiotic genus to better understand the contribution of individual probiotics to modulate blood glucose. We conducted a systematic review and meta-analysis of animal studies and human randomized controlled trials (RCTs) to assess the effects of Bifidobacterium (BF) probiotic supplementation on markers of glycemia. In a meta-analysis of 6 RCTs, BF supplementation had no effect on fasting blood glucose {FBG; mean difference [MD] = -1.99 mg/dL [95% confidence interval (CI): -4.84, 0.86], P = 0.13}, and there were no subgroup differences between subjects with elevated FBG concentrations and normoglycemia. However, BF supplementation reduced FBG concentrations in a meta-analysis comprised of studies utilizing animal models of obesity, MetS, or T2D [n = 16; MD = -36.11 mg/dL (CI: -49.04, -23.18), P < 0.0001]. Translational gaps from animal to human trials include paucity of research in female animals, BF supplementation in subjects that were normoglycemic, and lack of methodologic reporting regarding probiotic viability and stability. More research is necessary to assess the effects of BF supplementation in human subjects with elevated FBG concentrations. Overall, there was consistent evidence of the efficacy of BF probiotics to reduce elevated FBG concentrations in animal models but not clinical trials, suggesting that BF alone may have minimal effects on glycemic control, may be more effective when combined with multiple probiotic species, or may be more effective in conditions of hyperglycemia rather than elevated FBG concentrations.

Keywords: Bifidobacterium; blood glucose; hemoglobin A1c; metabolic syndrome; probiotics; type 2 diabetes mellitus.

FIGURE 1

Bifidobacterium supplementation does not affect fasting blood glucose in healthy animals. A forest plot shows the pooled mean difference between healthy animals treated with probiotic supplementation compared with no supplement controls. No influential studies were removed from the effect size estimate.

FIGURE 2

Bifidobacterium supplementation decreases fasting blood glucose in animal models with pathophysiology relevant to obesity, MetS, or T2D. A forest plot shows mean differences in 15 studies with models of DIO, MetS, or T2D with 1 potentially influential study (Hao et al. [70]) excluded from the effect size estimates.

FIGURE 3

Fasting blood glucose in probiotic-supplemented animal models with pathophysiology relevant to obesity, MetS, or T2D compared with healthy, untreated normal-weight animals. A forest plot shows mean differences of 12 DIO, MetS, or T2D studies with 1 potentially influential study (Hao et al. [70]) removed from the effect estimates.

FIGURE 4

Bifidobacterium supplementation does not affect fasting blood glucose in human subjects with hyperglycemia or normoglycemia. A forest plot is shown with subgroup and pooled mean differences of 6 RCTs (with 1 study reporting 2 Bifidobacterium strains). One influential study was excluded from the effect size estimates.