Gut microbiome signatures associated with type 2 diabetes in obesity in Mongolia

Mongolian people possess a unique dietary habit characterized by high consumption of meat and dairy products and fewer vegetables, resulting in the highest obesity rate in East Asia. Although obesity is a known cause of type 2 diabetes (T2D), the T2D rate is moderate in this population; this is known as the “Mongolian paradox.” Since the gut microbiota plays a key role in energy and metabolic homeostasis as an interface between food and body, we investigated gut microbial factors involved in the prevention of the co-occurrence of T2D with obesity in Mongolians. We compared the gut microbiome and metabolome of Mongolian adults with obesity with T2D (DO: n = 31) or without T2D (NDO: n = 35). Dysbiotic signatures were found in the gut microbiome of the DO group; lower levels of Faecalibacterium and Anaerostipes which are known as short-chain fatty acid (SCFA) producers and higher levels of Methanobrevibacter, Desulfovibrio, and Solobacterium which are known to be associated with certain diseases. On the other hand, the NDO group exhibited a higher level of fecal SCFA concentration, particularly acetate. This is consistent with the results of the whole shotgun metagenomic analysis, which revealed a higher relative abundance of SCFA biosynthesis-related genes encoded largely by Anaerostipes hadrus in the NDO group. Multiple logistic regression analysis including host demographic parameters indicated that acetate had the highest negative contribution to the onset of T2D. These findings suggest that SCFAs produced by the gut microbial community participate in preventing the development of T2D in obesity in Mongolians.