Gut microbiota alterations in adult individuals with obesity and insulin resistance: Its association with metabolic parameters and body compositions

An emerging body of evidence has highlighted the complex interplay among obesity, insulin resistance, and the gut microbiota. This observational study aimed to evaluate differences in intestinal microbiome profiles between individuals with obesity, with and without insulin resistance. Twenty individuals with obesity aged 20-50 years were enrolled and categorized according to insulin resistance status (N = 10 per group), as determined using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Fasting blood samples were collected and analyzed for glucose, lipid profiles, insulin, free fatty acids, and high-sensitivity C-reactive protein (hsCRP). Fecal DNA was extracted, and its quantity and quality were assessed.The V3-V4 region of 16s rRNA was amplified using specific primers, purified, and sequenced on the MiSeq Illumina platform with paired-end reads. The two groups showed notable disparities in fasting glucose (p=0.002), insulin (p<0.001), and HOMA-IR indices (p<0.001). While Alpha diversity remained comparable between groups when assessed using Shannon’s and Simpson’s indexes (but was significant for the Chao1 index), beta diversity was lower in the insulin-resistant group (p<0.05). Short-chain fatty acid-producing bacteria such as members of Lachnospiraceae family, Oscillospirales , and Faecalibacterium prausnitzii , were significantly enriched in insulin-sensitive individuals. In contrast, Alistipes putredenis was more abundant in those with insulin resistance. KEGG Orthology (KO) analysis revealed distinct functional enrichment: the Insulin Resistance group was enriched in carbohydrate metabolism pathways (e.g., glycolysis/gluconeogenesis, TCA cycle), while the Insulin Sensitive group showed more diverse metabolic activity, including amino acid and fatty acid metabolism, butyrate metabolism, and select carbohydrate pathways. These findings contribute to understanding the role of gut microbiota in metabolic heterogeneity associated with insulin resistance in obesity. • Beta diversity was significantly different between the groups, being lower in the Insulin- Resistance (IR) group, which indicates a distinct microbial community structure. • The study found two dominant enterotypes: the Prevotella genus and the Bacteroides genus. • The Insulin-Sensitive (IS) group was enriched in beneficial, short-chain fatty acid-producing bacteria, specifically members of the Lachnospiraceae family and species such as Faecalibacterium prausnitzii. • The Insulin-Resistant (IR) group had a higher abundance of proinflammatory bacteria, including Alistipes putredinis (also called Alistipes obesi ) and Escherichia–Shigella. • Predicted Functions: The microbiota in the IR group was enriched in carbohydrate metabolism pathways, whereas the IS group's microbiota showed greater activity in amino acid, fatty acid, and butyrate metabolism.