Insulin resistance modulates gut microbiota and incretin response remodeling after bariatric surgery in severe obesity.

Patients with high insulin resistance (Hi-IR) showed a higher relative abundance of Prevotella species at baseline compared to low insulin resistance (Lo-IR) patients.

• Participants were stratified based on HOMA-IR index: Hi-IR (HOMA-IR > 95th percentile) and Lo-IR (HOMA-IR < 25th percentile)
• Prevotella species have been previously associated with adverse metabolic and inflammatory profiles
• The two groups exhibited distinct microbiota profiles at baseline
• Study cohort consisted of 18 patients total (9 Hi-IR and 9 Lo-IR) with mean age 48.8 ± 9.2 years and mean BMI 45.03 ± 4.82 kg/m²
• All participants had severe obesity and normal glucose tolerance

Six months post-sleeve gastrectomy, the mean percentage of total weight loss was 26.5 ± 6% across the full study cohort.

• Both Hi-IR and Lo-IR groups achieved weight loss at 6 months post-surgery
• Body composition measurements were performed before and 6 months post-surgery
• Biochemical analyses were also conducted at both time points
• The study was a prospective single-center design

Both Hi-IR and Lo-IR groups exhibited enhanced secretion of GLP-1 and GLP-2 following a meal tolerance test (MTT) at 6 months post-surgery.

• Incretin responses were evaluated using a standardized meal tolerance test (MTT)
• Both glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) responses were assessed
• Enhanced GLP-1 and GLP-2 responses were correlated with weight loss and metabolic improvement
• These correlations were particularly pronounced in the Lo-IR population

Hi-IR patients experienced more pronounced changes in microbial diversity post-surgery, including increases in Akkermansia and Veillonella species and decreases in Prevotella species.

• Changes in microbial diversity were more pronounced in Hi-IR compared to Lo-IR patients
• Post-surgery increases in Akkermansia species were observed in the Hi-IR group
• Post-surgery increases in Veillonella species were observed in the Hi-IR group
• Post-surgery decreases in Prevotella species were observed in the Hi-IR group
• Both groups exhibited significant modifications in gut microbiota composition after surgery

Enhanced GLP-1 and GLP-2 responses were correlated with weight loss and metabolic improvement particularly in the Lo-IR population.

• The correlation between incretin responses and metabolic outcomes was more evident in the Lo-IR group than the Hi-IR group
• GLP-1 and GLP-2 responses were evaluated at baseline and 6 months post-surgery via standardized MTT
• Metabolic improvement was assessed through biochemical analyses at both time points
• These findings suggest that baseline insulin resistance state modulates post-surgical incretin-metabolic relationships

Gut microbiota composition at baseline differed between high and low insulin resistance groups in patients with severe obesity and normal glucose tolerance.

• The study specifically selected patients without diabetes (normal glucose tolerance) to isolate the effect of insulin resistance on microbiota
• Hi-IR group was defined by HOMA-IR > 95th percentile and Lo-IR by HOMA-IR < 25th percentile
• Distinct baseline microbiota profiles were identified between the two IR groups
• Microbiota assessments were performed before and 6 months post-surgery