Fecal Bacterial Community and Metagenome Function in Asians with Type 2 Diabetes, According to Enterotypes

Abstract

The role of gut microbes has been suggested in type 2 diabetes (T2DM) risk. However, their results remain controversial. We hypothesized that Asians with T2DM had different fecal bacterial compositions, co-abundance networks, and metagenome functions compared to healthy individuals, according to enterotypes. This hypothesis was examined using the combined gut microbiota data from human fecal samples from previous studies. The human fecal bacterial FASTA/Q files from 36 different T2DM studies in Asians were combined (healthy, n = 3378; T2DM, n = 551), and operational taxonomic units (OTUs) and their counts were obtained using qiime2 tools. In the machine learning approaches, fecal bacteria rich in T2DM were found. They were separated into two enterotypes, Lachnospiraceae (ET-L) and Prevotellaceae (ET-P). The Shannon and Chao1 indices, representing α-diversity, were significantly lower in the T2DM group compared to the healthy group in ET-L (p < 0.05) but not in ET-P. In the Shapley additive explanations analysis of ET-L, Escherichia fergusonii, Collinsella aerofaciens, Streptococcus vestibularis, and Bifidobacterium longum were higher (p < 0.001), while Phocaeicola vulgatus, Bacteroides uniformis, and Faecalibacterium prausnitzii were lower in the T2DM group than in the healthy group (p < 0.00005). In ET-P, Escherichia fergusonii, Megasphaera elsdenii, and Oscillibacter valericigenes were higher, and Bacteroides koreensis and Faecalibacterium prausnitzii were lower in the T2DM group than in the healthy group. In ET-L and ET-P, bacteria in the healthy and T2DM groups positively interacted with each other within each group (p < 0.0001) but negatively interacted between the T2DM and healthy groups in the network analysis (p < 0.0001). In the metagenome functions of the fecal bacteria, the gluconeogenesis, glycolysis, and amino acid metabolism pathways were higher, whereas insulin signaling and adenosine 5′ monophosphate-activated protein kinase (AMPK) signaling pathways were lower in the T2DM group than in the healthy group for both enterotypes (p < 0.00005). In conclusion, Asians with T2DM exhibited gut dysbiosis, potentially linked to intestinal permeability and the enteric vagus nervous system.