Gut Microbiota Compositions and Modulation of Bacterial Metabolic Functional Genes in Type -2 Diabetes Mellitus Individuals at Nnewi, Anambra State, Nigeria

ABSTRACT

Background: There is paucity of information on the gut microbiota compositions of Type 2 Diabetes Mellitus (T2DM) subjects in South East of Nigeria, with Next-Generation Sequencing technology (NGS). Gut microbiota dysbiosis  has   been associated with metabolic disorders, such as obesity, insulin resistance and T2DM. The objectives of this study are to determine gut microbiome compositions in T2DM individuals and healthy controls and to predict bacterial metabolic functional gene variations. Methods: Stool samples were   collected from 110 confirmed T2DM and 10 non-T2DM subjects and bacterial DNA extracted. The V4 regions of bacterial 16S rRNA were amplified and sequenced using Illumina NextSeq 500 platform. The raw pair-end FASTQ sequence files were imported into EzBioCloud pipeline and Illumina BaseSpace for taxonomic identification. Results: The species richness or alpha diversity were lower in T2DM subjects when compared with the healthy controls. Similar trend was observed in phylogenetic diversity and Shannon index. Firmicutes (63.21% vs 64.89%) were the most abundant in the gut of both T2DM and healthy controls, followed by Bacteroidetes (18.46% vs 22.35%), Proteobacteria (12.77% vs 6.93%), and Cyanobacteria (2.24% vs 1.71%). There was significant lower relative abundance of Bifidobacterium pseudolongum, Romboutsia timonensis, Blautia coccoides and others as a marker in T2D patients than healthy controls. The relative abundance of Bacteriodes vulgatus, Prevotella copri were significantly higher (p< 0.05) among T2DM subjects than Non-T2DM subjects. Lactobacillus mucosae, L. salivarius and Lactococcus lactis were significantly higher in T2DM subjects. Over 156 metabolic functional genes were significantly downregulated in T2DM subjects, and bacterial gene ortholog K20890- xylan alpha-glucuronosyltransferase involved in the metabolism of non-digestible fibre was turned off in T2DM patients. Conclusion: The high abundance of Prevotella copri and low abundance of Akkermansia  muciniphila in T2DM represents intestinal pathobionts signatures associated with T2DM development. Butyrate and propionate-producing bacteria found in lower abundance in T2DM offer support for dietary or probiotics intervention.