– By Kranti Karande
Type 2 diabetes (T2D) is the most common type of diabetes. People who have T2D are said to have insulin resistance. T2D is a chronic condition that affects blood sugar (glucose) absorption and lipid metabolism.
Recently the gut microbiome was identified as an important factor for T2D development. Disruption of the balance between gut microbes has been linked to the development of metabolic diseases, in particular T2D, obesity and cardiovascular disorders. Some of the earlier studies observed dissimialrity between the gut microbiome of diabetics, prediabetics, and healthy nondiabetic individuals, although very few investigated the gut microbiome of treatment-naive individuals with T2D.
In this study, scientists have analyzed ND, PreDMs, NewDMs, and KnownDMs gut microbiome to understand and identify differences in the T2D, and prediabetes-associated microbial community. The scientists also looked at the community changes in microbial association networks and identified genera which are contributing for the transition from healthy (control) to diabetic state here called as driver taxa. They also analyzed the association of a wide array of serum biomarkers with genera, which were differentially abundant and were also found to be contributing for the major changes in the gut microbiome of T2D individuals .
In this study, a total of 102 subjects were studied, and they looked at the gut microbiota of prediabetics (PreDMs) (n= 17), newly diagnosed diabetics (NewDMs) (n = 11), and diabetics on antidiabetic treatment (KnownDMs) (n = 39) and compared them with healthy nondiabetics (ND) (n= 35). Twenty-five different serum biomarkers were measured to assess the status of diabetes and their association with gut microbiota.
The research identified nine separate genera in four sample groups as having differential abundance. Among them, Akkermansia, Blautia, and Ruminococcus were found to be significantly decreased, while Lactobacillus was increased in NewDMs compared to ND and recovered in KnownDMs. Akkermansia was inversely correlated with HbA1c and positively correlated with total antioxidants. Compared to ND, there was increased abundance of Megasphaera, Escherichia, and Acidaminococcus and decreased abundance of Sutterella in KnownDMs.
Among many taxa known to act as community drivers during disease progression, it was observed that genus Sutterella is a common driver taxon among all diabetic groups. On the basis of the results of random forest analysis (methodology) , they discovered that the serum metabolites fasting glucose, HbA1c, methionine, and total antioxidants were highly discriminating factors among studied groups. The compiled data showed that the gut microbial diversity of NewDMs is substantially different from that of ND but not of PreDMs. Interestingly, after anti-diabetic treatment, the microbial diversity of KnownDMs tends to recover toward that of ND.
Gut microbiota is thought to play a role in the development of the disease, and previous studies have documented a microbiome dysbiosis association with T2D. In this study, scientists have attempted to investigate gut microbiota of ND, PreDMs, NewDMs, and KnownDMs. They found that the genera Akkermansia and Blautia decreased significantly in treatment-naive diabetics and were restored in KnownDMs on antidiabetic treatment. Understanding the transition of microbiota and its association with serum biomarkers in diabetics with different disease states may pave the way for new therapeutic approaches for T2D.
Twenty-five different serum biomarkers were checked and compared with the gut microbiota to assess the different states of diabetes. Targeted 16S rRNA amplicon sequencing was used to assess the microbial diversity, community shuffling, and identification of driver taxa for the disease state. They have investigated relationships between a wide array of serum biomarkers responsible for progression of T2D with significantly diverged and differentially abundant taxa in each study group. Significantly different patterns were observed in the gut microbiota of PreDMs, NewDMs, and KnownDMs compared to ND. In KnownDMs, abundance of some microbial taxa was found to be similar to that of ND group.
Since oxidative stress is known to be involved in the establishment of insulin resistance and diabetic complications , they also measured total antioxidant capacity and lipid peroxides, a marker of oxidative damage to lipids in the blood. Interstingly, they found a significant decrease in total antioxidant capacity and increase in lipid peroxidation in treatment-naive NewDMs but not in PreDMs. In KnownDMs on treatment with metformin, an increase in total antioxidant capacity and decrease in lipid peroxidation were observed.
These findings show differences in the gut microbiome in PreDMs, NewDMs, and KnownDMs compared to ND. In PreDMs, the gut microbiota doesn’t show a significant difference when compared with ND, while in NewDMs, both abundance and diversity have changed significantly, which seems to be restored to some degree in KnownDMs on antidiabetic care.