Probiotics in the prevention and management of obesity and type 2 diabetes mellitus

Abstract

Abstract Background: Shifts in the gastrointestinal microbiome have been shown to contribute to the progression of metabolic diseases including prediabetes and type 2 diabetes mellitus. Research suggests that in vivo modulation of the gut microbiome by specific probiotic microorganisms may improve insulin sensitivity and blood sugar management, preventing or delaying the development of type 2 diabetes mellitus. However, further research is needed to understand the effect of probiotics as a therapy for the treatment of metabolic diseases. The overall aim of this thesis was to develop and assess the efficacy of an evidence-based multi-strain probiotic in vitro and in vivo. This probiotic was developed to encourage a shift in the gastrointestinal microbial cohort from a disease-prone to a balanced state with the aim of improving metabolic markers associated with type 2 diabetes mellitus. Methods: Three studies were conducted to assess this aim. Study 1 (Chapter 2) is a systematic review of randomised clinical trials to identify the probiotics with the greatest anti-obesity and anti-diabetic effects and consequently develop a multi-strain probiotic. Study 2 (Chapter 3) describes a series of in vitro experiments that investigate the effect of metabolites in the supernatant from the multi-strain probiotic on glucose uptake and lipid accumulation in muscle cells and adipocytes. Study 3 (Chapter 4) describes a double-blind, placebo-controlled pilot study aimed to assess the effect of the multi-strain probiotic on metabolic and inflammatory markers and the intestinal microbial profile of participants with obesity, prediabetes and recently diagnosed with type 2 diabetes mellitus. Results and discussion: Study 1 found that a multi-strain probiotic containing L. bulgaricus, L. gasseri, L. plantarum, B. breve, B. bifidum, B. lactis, S. thermophilus and Saccharomyces boulardii might have anti-obesity, anti-diabetic and anti-inflammatory effects. Study 2 found the supernatant from this probiotic decreased lipid accumulation in adipocytes and partially restored glucose uptake in insulin resistant skeletal muscle cells. Study 3 found the multi-strain probiotic did not decrease blood glucose levels, however it did improve insulin sensitivity, gut permeability and the production of gut microbial-derived metabolites in participants recently diagnosed with type 2 diabetes mellitus and produced a beneficial shift in the intestinal microbial profile of those taking metformin. Conclusion: Intentional manipulation of beneficial microbes and microbial-derived metabolites in the intestine using an evidence-based multi-strain probiotic may be useful in managing insulin resistance.