The Gut Microbial Diversity of Newly Diagnosed Diabetics but Not of Prediabetics Is Significantly Different from That of Healthy Nondiabetics.

Type 2 diabetes (T2D) is a complex metabolic syndrome characterized by insulin dysfunction and abnormalities in glucose and lipid metabolism. The gut microbiome has been recently identified as an important factor for development of T2D. In this study, a total of 102 subjects were recruited, and we have 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. Our analysis revealed nine different genera as differentially abundant in four study groups. Among them, Akkermansia, Blautia, and Ruminococcus were found to be significantly (P < 0.05) 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, we observed genus Sutterella as a common driver taxon among all diabetic groups. On the basis of the results of random forest analysis, we found that the genera Akkermansia and Sutterella and that the serum metabolites fasting glucose, HbA1c, methionine, and total antioxidants were highly discriminative factors among studied groups. Taken together, our data revealed that gut microbial diversity of NewDMs but not of PreDMs is significantly different from that of ND. Interestingly, after antidiabetic treatment, the microbial diversity of KnownDMs tends to recover toward that of ND.IMPORTANCE Gut microbiota is considered to play a role in disease progression, and previous studies have reported an association of microbiome dysbiosis with T2D. In this study, we have attempted to investigate gut microbiota of ND, PreDMs, NewDMs, and KnownDMs. We found that the genera Akkermansia and Blautia decreased significantly (P < 0.05) in treatment-naive diabetics and were restored in KnownDMs on antidiabetic treatment. To the best of our knowledge, comparative studies on shifts in the microbial community in individuals of different diabetic states are lacking. 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.

Type 2 diabetes and gut microbiome: at the intersection of known and unknown.

The prevalence of metabolic syndrome is increasing rapidly across the globe. Though the prevalence of the disease is similar in population of upper middle income and high income countries, the age of affected population is lower in upper middle income countries. This is attributed to genetic as well as changing life style factors. The contributing factors for type 2 diabetes range from genetic/epigenetic disposal, intra uterine nutrition, dietary pattern to sedentary lifestyle. The role of the gut microbiota in metabolic disorders is increasingly gaining importance. Several studies have reported significant difference in the profile of the gut microbiota in Caucasian population considering obese and type 2 diabetic populations while limited number of studies are available on populations from the developing world. The metabolites from the gut microbes contribute to the gut barrier integrity and a compromised barrier leads to leakage of inflammatory mediators into systemic circulation and hence increases insulin resistance. Attempts have been made at correcting metabolic syndrome through dietary changes by altering the gut microbiota with some success. This report is an attempt to explain the hypothesis of compromised nutrition altering the gut microbiota, gut metabolites, gut barrier function, systemic inflammation and hence insulin response.

Adiponectin and IL-6: Mediators of inflammation in progression of healthy to type 2 diabetes in Indian population.

Aim The objective of the study was to identify the association if any, of inflammatory markers (adiponectin and IL-6) with fasting glucose in normoglycemic (healthy), prediabetic (impaired fasting glucose), and hyperglycemic (diabetic) people in Indian population. Methods Total 162 volunteers were distributed into 3 groups (normoglycemic, individuals with impaired fasting glucose, and hyperglycemic) as per ADA criterion. The blood chemistry parameters were analyzed and serum adiponectin and IL-6 levels were measured by ELISA. Results Significant reduction was observed in serum adiponectin level in hyperglycemic and impaired fasting glucose population compared with normoglycemic population. Significant reduction in adiponectin was also observed in impaired fasting glucose group compared with hyperglycemic group. Similarly significant increase was also observed in IL-6 level in hyperglycemic and impaired fasting glucose groups compared with normoglycemic group. Conclusions From our data it can be summarized that there is a significant change in both adiponectin (reduction) and IL-6 (increase) levels in normoglycemic (healthy), prediabetic (impaired fasting glucose), and hyperglycemic (diabetic) population in Indian population. There is a significant but gradual change during the progression of healthy toward diabetic population via pre-diabetic condition.