BACKGROUND: Bariatric surgery is the most long-term effective treatment option for severe obesity. The role of gut microbiome (GM) in either the development of obesity or in response to obesity management strategies has been a matter of debate. This study aims to compare the impact of two of the most popular procedures, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (GB), on metabolic syndrome parameters and gut bacterial microbiome and in systemic immuno-inflammatory response. METHODS: A prospective observational study enrolled 24 patients with severe obesity, 14 underwent SG and 10 GB. Evaluations before (0 M) and 6 months (6 M) after surgical procedures included clinical and biochemical parameters, expression of 17 immuno-inflammatory genes in peripheral blood leukocytes, and assessment of gut microbiome profile using 16 s rRNA next-generation sequencing approach. Statistical significance was set to a p value <
0.05 with an FDR <
0.1. RESULTS: A significant and similar decrease in weight-associated parameters and for most metabolic markers was achieved with both surgeries. Considering the gut microbiome in the whole study population, there was an increase in alpha diversity at family-level taxa. Beta diversity between SG and GB at 6 M showed near significant differences (p = 0.042) at genus levels. Analysis of the relative abundance of individual taxonomic groups highlighted differences between pre- and post-surgical treatment and between both approaches, namely, a higher representation of family Enterobacteriaceae and genera Veillonella and Enterobacteriaceae_unclassified after GB. Increased expression of immune-inflammatory genes was observed mainly for SG patients. CONCLUSIONS: We conclude that SG and GB have similar clinical and metabolic outcomes but different impacts in the gut bacterial microbiome. Results also suggest reactivation of immune response after bariatric surgery.