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

Abstract

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.

Keywords: dysbiosys; gut metabolites; malnourishment; nutrition; obesity.

Figure 1.

Number of people with diabetes in millions classified based on income groups, IDF 2013. The number of people with diabetes is similar in High income and upper middle income countries but the affected age group is lower in population of lower middle income countries, impacting the economy of the corresponding countries (Source: IDF 2013).

Figure 2.

Number of deaths due to diabetes in thousands in 2013 classified based on income groups, IDF. The mortality due to diabetes is significantly higher in population of lower middle income countries compared to higher income countries (Source IDF 2013).

Figure 3.

Proportion of different phyla of bacteria in the gut at different stages of life (Adapted from reference 15). Firmicutes (F); Bacteroidetes (B); Actinobacteria (A); Proteobacteria (P); Others (O). Human gut microbiota changes at different stages of life and also influenced by different factors like age, dietary habits, environment and medicines. The succession of microbiota from babies to centenarians and the influence of diet, drug, nutrition and illness on the diversity of microbiota are depicted.

Figure 4.

Major differences in the gut microbiota profile between the least developed, developing and dev;loped representative countries.The transformation of the gut microbiota in children to that of adult gut microbiota happens in the span of first 3 years of life. The functionality of the microbiota in children focused on enzymes of folic acid biosynthesis while in adults, the focus was on biosynthesis of biotin, cobalmin and thiamine and breakdown of folic acid. Malawian and Amerindian flora were very similar to that of herbivorous mammals. Enzymes for anabolism of metabolites like riboflavin synthesis, glutamate synthesis and amylase were highly represented. Gut microbiota of USA population is similar to carnivorous mammals, (enzymes for catabolism of metabolites like enzymes for degradation of amino acids, glycan degradation were highly represented).