Can gut bacteria be used for early diagnosis of type 2 diabetes?

The prevalence of type 2 diabetes (T2D) is increasingly rapidly around the globe and has challenged researchers to investigate the underlying pathophysiological mechanisms. The T2D pandemic closely tracks the rise of obesity, not only in Europe and USA but also in the developing world. Among environmental factors that contribute to T2D susceptibility, intestinal microbiota has been the focus of several recent studies.

 

The available scientific evidence suggests that gut microbiota has a role in the regulation of the energy homeostasis, and microbial dysbiosis has been associated with various metabolic disorders, including T2D and obesity. For instance, it has been shown that the ratio of Bacteroidetes to Firmicutes species is linked to T2D and fasting blood sugar (FBS), and it is also important to consider that a larger number of opportunistic pathogens and a lower number of butyrate-producing bacteria are attributed to presence of diabetes. Individuals with T2D have consistently shown a gut microbiota characterized by a decreased abundance of butyrate-producing bacteria, in particular Faecalibacterium prausnitzii, and Bifidobacterium species. However, mechanisms that link the gut microbiota with metabolic diseases such as T2D have not been fully elucidated. Thus, it is unclear whether a given microbiota composition causes T2D in humans or whether microbial dysbiosis is only a symptom of metabolic disease.

 

Until now, studies associating the microbiome with T2D have examined individuals with well-established disease as compared to particularly healthy individuals. Changes in microbial composition and function in the sub-clinical state, prior to the onset of disease, have never been examined. A recent study, which was led by Dr. Curtis Huttenhower from the Broad Institute in Cambridge (USA), found that microbial changes that occur prior to the onset of T2D may potentially be used for early diagnosis and intervention. A total of 36 faecal samples from 20 identical (monozygotic) healthy Korean twins aged 30-48 years were collected at the beginning of the study, and for 16 individuals another sample was obtained 12-44 months later. During the course of the study, the range of T2D clinical markers varied from healthy to near-clinical values and allowed researchers to investigate for the first time how the function and composition of the gut microbiota vary at different stages before the onset of the disease. Data was analysed across the whole cohort and the researchers knew outcomes’ differences were not attributable to genes because all twin pairs diverged in their T2D markers and gut microbiota. The researchers found associations between microbial composition and function and both the pre- and post-onset range of T2D-related biomarkers such as body mass index (BMI), FBS, and the derived homeostasis model assessment (HOMA) index. For instance, BMI was negatively correlated with the abundance of mucin-degrading Akkermansia muciniphila and positively correlated with riboflavin and nicotinamide adenine dinucleotide (NAD) biosynthesis. Indeed, they found that changes in the gut microbiota observed in patients with established T2D (in other studies) are already present prior to the onset of the disease, which suggests that shifts in the gut microbial communities prior to full disease onset may be either causal or an early correlative indicator. Furthermore, a substantial subset of microbial species, but not specific strains, was shared between twins. This fact can be explained by early colonization by the same strains with subsequent genetic divergence over the course of evolution. In conclusion, compositional and functional microbial signatures prior to the onset of T2D may represent a novel marker for early diagnosis. These findings corroborate the idea that the ability to detect microbial changes before T2D symptoms develop may provide a new way to potentially reduce the time between T2D detection and onset, thus mitigating the effects of the disease.

 

As patients with T2D show an alteration in their gut microbial composition, probiotics have emerged as a potential way of improving glucose metabolism through modifying gut microbiota. There have been reported positive glycemic effects of probiotics among individuals with diabetes. A recent meta-analysis of randomised placebo-controlled trials suggests that probiotics are effective in reducing the glucose metabolic factors associated with diabetes. Studies included measured glucose, HbA1c, HOMA-IR and insulin as outcome variables and examined healthy participants and participants with diabetes or diabetic risk factors. Probiotic effectiveness was higher when they were used in the capsule form and with multiple bacterial strains. Another meta-analysis of randomized controlled trials concluded that probiotics have a modest role in improving glucose metabolism and a greater effect was observed with a duration of intervention equal to or higher than 8 weeks. Despite these promising findings, further research is needed in order to determine whether probiotics may be used as an adjunct therapy for glycaemic control in addition to pharmaceutical drug intake for patients with diabetes.

 

In conclusion, alteration of microbial composition and function in patients with T2D appears to be a key feature in the pathogenesis of the disease. Although it is yet to be proven that intestinal bacteria play a causal role in the development of T2D, dietary interventions such as probiotic foods or supplements have the potential to modulate gut microbiota for T2D prevention and treatment.

 

 

References:

 

Brahe LK, Astrup A, Larsen LH. Can we prevent obesity-related metabolic diseases by dietary modulation of the gut microbiota? Adv Nutr. 2016;7:90-101.

 

Mazidi M, Rezaie P, Kengne AP, Mobarhan MG, Ferns GA. Gut microbiome and metabolic syndrome. Diabetes Metab Syndr. 2016. doi:10.1016/j.dsx.2016.01.024.

 

Sun J, Buys NJ. Glucosa- and glycaemic factor-lowering effects of probiotics on diabetes: a meta-analysis of randomised placebo-conrolled trials. Br J Nutr. 2016;115(7):1167-77.

 

Yassour M, Lim MY, Yun HS, et al. Sub-clinical detection of gut microbial biomarkers of obesity and type 2 diabetes. Genome Med. 2016;8:17.

 

Zhang Q, Wu Y, Fei X. Effect of probiotics on glucose metabolism in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials. Medicina (Kaunas). 2016;52(1):28-34.

Andreu Prados
Andreu Prados
Andreu Prados holds a Bachelor of Science Degree in Pharmacy & Human Nutrition and Dietetics. Science writer specialised in gut microbiota and probiotics, working also as lecturer and consultant in nutrition and healthcare. Follow Andreu on Twitter @andreuprados