Targeting the gut microbiome: A new approach to treating diabetes

A recent Nutrients study reviews the crucial role of gut microbiota in the pathogenesis and management of diabetes mellitus (DM).

Study: Exploring the Significance of Gut Microbiota in Diabetes Pathogenesis and Management—A Narrative Review. Image Credit: Troyan / Shutterstock.com

The role of the gut microbiome in diabetes

Previous studies have shown that type 2 DM (T2DM) could be associated with certain compositional changes in the gut microbiota, including lower levels of phylum Firmicutes and Clostridia in the gut microbiota of T2DM patients as compared to controls.

Positive correlations were also noted between the ratios of Bacteroides-Prevotella to C. coccoides-E. rectale and Bacteroidetes to Firmicutes and plasma glucose concentrations. In T2DM patients, Betaproteobacteria was more prevalent, which positively correlated with lower glucose tolerance.

A Chinese metagenome-wide association study (MGWAS) reported microbial dysbiosis in T2DM patients. To this end, intestines of T2DM patients exhibited a greater presence of certain pathogens including Clostridium hathewayi, Bacteroides caccae, Eggerthella, lenta Clostridium ramosum, Clostridium symbiosum, and Escherichia coli.

Simultaneously, a marked reduction in butyrate-producing bacteria including Faecalibacterium prausnitzii, Clostridiales sp. SS3/4, E. rectale, Roseburia inulinivorans, and Roseburia intestinalis was observed. In the gut microbiome of T2DM patients, a higher number of mucin-degrading species and sulfate-reducing species was also reported.

In a previous study of European women with T2DM, reduced levels Faecalibacterium prausnitzii and Roseburia intestinalis was confirmed. Furthermore, reduced concentrations of five Clostridium species and greater abundance of four Lactobacillus species was observed.

The correlation between Clostridium and glycosylated hemoglobin (HbA1c), C-peptide, plasma triglycerides, and insulin was negative, with HbA1c positively correlated with Lactobacillus levels. Taken together, these findings suggest that these microbial species could be associated with the development of T2DM.

Dysbiosis affects the pathogenesis of T2DM through various molecular mechanisms. For example, gut microbiota can influence lipid and glucose metabolism, thereby affecting the development of T2DM. These effects can be evoked by important regulators such as bile acids, branched-chain amino acids (BCAAs), short-chain fatty acids (SCFAs), and bacterial lipopolysaccharide (LPS).

Gut microbiota as a therapeutic target for diabetes

Probiotics improve glycemic control and insulin sensitivity, particularly among diabetics and those at risk of developing diabetes.

Certain bacterial strains such as Lactobacillus acidophilus and Bifidobacterium bifidum have been associated with beneficial effects on multiple metabolic processes. A key mechanism of action is the reaction between SCFAs and G-protein-coupled receptors, which enhances insulin sensitivity. Therapeutic strategies that target sirtuin 1 (SIRT1) activity have also shown promising results in improving insulin sensitivity and glycemic control in diabetics.

Fetuin-A, which is a liver-derived protein, can mute insulin signaling, with higher levels of fetuin-A associated with insulin resistance and increased inflammation. One randomized controlled trial found that Lactobacillus casei supplementation for eight weeks led to reduced fetuin-A levels, increased SIRT1, as well as improved insulin resistance and both insulin and postprandial blood glucose concentrations. L. casei has also been shown to possess anti-inflammatory properties, with previous studies reporting reduced levels of inflammation markers like C-reactive protein (CRP) and tumor necrosis factor α (TNF-α) following L. casei supplementation.

Synbiotics are combinations of probiotics and prebiotics that also offer a promising approach to managing diabetes. One study on diabetics undergoing hemodialysis showed that synbiotic supplementation significantly lowered insulin concentrations, fasting blood glucose levels, and insulin resistance while also increasing insulin sensitivity.

Fecal microbiota transplantation (FMT), which involves fecal bacteria from a healthy individual transplanted to another individual, has been investigated for the treatment of T2DM. One study showed that FMT, both independently and in combination with metformin, led to significant improvements in key clinical indicators in T2DM patients, including reduced body mass index (BMI) values, both pre- and postprandial blood glucose levels, as well as HbA1c concentrations.

Diet and exercise can also have significant effects on the composition of the gut microbiota. Whole grains and high-fiber diets support a beneficial and diverse microbial environment, which leads to the production of SCFAs that can reduce inflammation and improve insulin sensitivity.

The gastrointestinal microbiota is also affected by regular exercise, which can enhance blood glucose regulation. In fact, mouse models have demonstrated that exercise leads to the production of SCFAs and restore gut health.

Conclusions

The review findings indicate that the mechanism of microbiome dysbiosis could be a potential factor in the pathogenesis of T2DM, thus presenting novel treatment options for microbiota-targeted interventions. To develop better personalized medical interventions, more research is needed to understand better the role of gut microbiome disruption in the pathogenesis and progression of T2DM.