The prevalence of pre-diabetes is increasing worldwide, and more than 482 million may develop it by 2040. Prediabetes occurs when blood glucose levels are higher than normal but not high enough to make a diagnosis of type 2 diabetes mellitus (T2DM). Prediabetes is of concern, as people with this condition are at high risk of developing T2DM and complications.
Metformin, a drug commonly prescribed for treating T2DM, is known to act by reducing hepatic glucose production, but recent evidence suggests that some of the antidiabetic effects of metformin are also associated with changes in the intestinal microbiome. Lifestyle interventions that produce weight loss have been shown to reduce the risk of developing T2DM by 30–58% in subjects with prediabetes.
The effectiveness of such interventions may be enhanced by targeting environmental factors such as the intestinal microbiota, which has been proven to predict the response to lifestyle interventions and play a part in mediating the glucose-lowering effects of metformin. As a consequence, the intestinal microbiota is postulated as a therapeutic target for prediabetes and early diagnosed T2DM.
A collaborative team of researchers from Australia and the USA aimed to investigate the effect of a multi-strain probiotic (L. plantarum, L. bulgaricus, L. gasseri, B. breve, B. animalis sbsp. lactis, B. bifidum, S. thermophilus, and S. boulardii) on glycemic, inflammatory, and permeability markers in adults with prediabetes and early T2DM and to assess whether the probiotic can enhance metformin’s effect on glycaemia.
They carried out a randomised controlled pilot study, published in the journal 'Nutrients', in 60 adults with a BMI ≥ 25 kg/m2 and with pre-diabetes or T2DM.
The participants were randomised to a twice daily probiotic supplement (5 × 1010 CFU/dose in a capsule) or a placebo for 12 weeks. They found that participants given the probiotics demonstrated an increased production of butyrate, which could consequently enhance glucose management.
The report states: "The findings partly clarify the possible mechanisms by which probiotics may assist as an adjunct supplement to metformin in the management of individuals with high blood glucose levels."
Analyses of the primary outcome (fasting plasma glucose) and secondary outcomes, included circulating lipopolysaccharide, zonulin, and short chain fatty acids as well as a metagenomic analysis of the fecal microbiome were performed at baseline and 12 weeks post-intervention.
Participants were also asked to record their food intake and the total number of steps walked in a study diary.
The results showed no significant differences in the primary and secondary outcome measures between the probiotic and placebo group.
An analysis of a subgroup of participants taking metformin showed a decrease in fasting plasma glucose, HbA1c, insulin resistance, and zonulin; an increase in plasma butyrate concentrations; and an enrichment of microbial butyrate-producing pathways in the probiotic group but not in the placebo group.
The report concludes: "Although no significant changes in metabolic, inflammatory and permeability markers between the probiotic and placebo groups were observed, significant improvements in the fasting plasma glucose, insulin resistance, and permeability marker zonulin were found in the participants taking metformin and the probiotic together, with beneficial shifts in SCFA-producing bacteria.
"This study provided suggestive pilot data that probiotics may enhance the efficacy of metformin and regulate butyrate production in those with prediabetes and recently diagnosed T2DM. The findings reported partly clarify the possible mechanisms by which probiotics may assist as an adjunct supplement to metformin in the management of individuals with high blood glucose levels."
The researchers note that more than 70% of the participants were considered compliant (taking ≥80% of the study products) and no one took less than 50% of the recommended dosage, but they recommend that further long-term studies with additional follow-up visits to increase adherence to the treatment regimens are required to confirm the outcomes of this study.
They also note that probiotics are transient colonisers and the wash-out of administered doses can take approximately 4–6 weeks, thereby leading to a therapy that may not be permanent. The report states: "This implies that for lasting or perhaps significant effects, probiotics need to be taken for a longer term."
Palacios. T., et al
"Targeting the Intestinal Microbiota to Prevent Type 2 Diabetes and Enhance the Effect of Metformin on Glycaemia: A Randomised Controlled Pilot Study"