Trio Of Recent Studies Uncover Truths About The Gut Microbiome and T2DM 

Three recent studies reveal insights into potential links between the gut microbiome and type 2 diabetes mellitus (T2DM).  

Researchers have shown increasing interest in examining the role of intestinal flora in various health outcomes. The studies highlighted here investigate how gut bacteria influence the development of T2DM.  

The first is a metastudy of the most reliable microbiome literature, which looks at associations of different bacterial genera and T2DM. The second study presents evidence that bacterial translocation across the intestinal barrier may contribute to the development of T2DM. The third study looked for bacterial metabolites that can act as biomarkers for either type 1 or type 2 diabetes. As a result, they may have discovered a potential new treatment for T2DM. Collectively, these studies describe an important connection between the bacteria living in our gut and the pathophysiology of T2DM.  

The metastudy investigating links between gut bacteria and T2DM was conducted by a research team from Oregon State University and was published in EBioMedicine. The goal of the study was to find specific bacteria that may indicate positive metabolic outcomes related to T2DM. There was a large amount of variation in the 42 human studies included in the paper. However, some patterns were observed. Bacteroides and Bifidobacterium are two genera that may be protective against T2DM. In nearly all the studies, levels of Bifidobacterium were high in healthy subjects and low in subjects with T2DM. The three genera most commonly found in higher levels in T2DM patients were Ruminococcus, Fusobacterium, and Blautia. The genus Lactobacillus exhibited species–specific effects, with some species being found at high levels in T2DM patients and other species being found in low amounts. There may be synergistic effects of multiple species or genera of bacteria working together to protect against T2DM. The authors conclude that personalized medicine may be necessary for this field because the impact of bacterial species on T2DM may vary from person to person. Further research is needed in this area. 

The second study in this trio examined bacteria loads in tissue from 40 subjects with obesity. Twenty of these subjects had T2DM and the other 20 had normal blood glucose levels. The study, published in Nature Metabolism, sampled plasma, liver tissue, and three types of adipose tissue from each subject. They found that subjects with diabetes had much higher bacterial loads in liver and omental adipose tissue than those without diabetes. Omental tissue is fat connecting the stomach and the transverse colon. The authors hypothesize that gut bacteria cross the intestinal barrier, which is more permeable in patients with obesity, and become lodged in this tissue. The resulting inflammatory response inhibits insulin from regulating blood glucose levels. This process, called bacterial translocation, may be an important step in the progression of T2DM. This insight presents a potential new strategy for the prevention of T2DM. Researchers should investigate whether this bacterial translocation can be blocked, and if it can, what impact does that have on the development of T2DM?  

A third study looking at the relationship between intestinal bacteria and diabetes focuses on the role of bacterial metabolites. Researchers from McGill University, Kyoto University, and INSERM/University of Paris, investigated several bacterial metabolites and their association with either type 1 diabetes mellitus (T1DM) or T2DM. After examining blood samples from 148 subjects, the researchers identified one metabolite, 4-Cresol, as having a potential protective effect against T2DM. Levels of 4-Cresol were lower in diabetic subjects. Furthermore, animal testing has shown that low doses of 4-Cresol increase the proliferation of pancreatic beta cells, improve glycemic control, and may cause weight loss. Pancreatic beta cells are the cells that produce insulin. This bacterial metabolite may, therefore, represent a new therapy for treating T2DM.  

Taken together, the results of these three studies expose a clear link between gut microbes and T2DM. However, they also reveal the complexity of this relationship and the need for additional research. The species of bacteria in our guts, the location of these bacteria, and the types of metabolites they produce, all influence our susceptibility or resistance to developing T2DM. By investigating the mechanisms linking gut bacteria and T2DM, these researchers are discovering novel therapies that could treat or slow the progression of this pervasive disease.  

Practice Pearls: 

• Bacterial translocation from the intestine to the liver and omental tissue may be a critical step in the progression of T2DM 
• Bifidobacterium and Lactobacillus bacteria may exhibit synergistic protective effects against T2DM 
• The bacterial metabolite 4-Cresol stimulates proliferation of pancreatic beta cells and may work as a novel T2DM therapy 

Halidy, Rich. “Gut Microbiome Studies Reveal New Bacterial Links with Diabetes.” New Atlas, Nature Metabolism, 11 Mar. 2020, newatlas.com/science/gut-microbiome-bacteria-diabetes-metastudy-metabolism/. 

Mit Suthar, PharmD. Candidate, LECOM School of Pharmacy 

See more about the gut microbiome and type 2 diabetes.