Specific microbes shift links to sustained weight loss and metabolic improvement after sleeve gastrectomy

Abstract Sleeve gastrectomy (SG) is a highly effective treatment for intractable obesity. However, gut microbiome alterations and their roles in post-SG metabolic improvement remain controversial. This study investigated the metabolic, inflammatory, and gut microbiome alterations in a cohort of 108 patients before and six months after SG. SG led to significant improvements (P < 0.001) in body composition (weight, BMI, waist circumference, WHR), glucose metabolism (FBG, HbA1c), blood lipids (TG, HDL), blood pressure (SBP, DBP), and inflammatory markers (WBC, NEUC, CRP). Metagenomic analysis of fecal samples revealed significant post-surgical shifts in the gut microbiome, characterized by a significant increase in alpha diversity and a restoration of microbial gene richness. At the phylum level, Bacillota , Fusobacteriota , and Verrucomicrobiota increased, while Actinobacterota and Pseudomonadota decreased. Differential analysis identified 19 species that significantly distinguished pre- and post-operative states (AUC > 0.8), notably featuring the upregulation of Haemophilus_D , Veillonella , Akkermansia and Streptococcus , and the downregulation of Phocaeicola , Enterocloster , Gemmiger , and Escherichia coli . Functionally, upregulated microbes were enriched for propanoate metabolism and lipogenesis suppression pathways, whereas downregulated microbes were associated with inflammatory response regulation. These microbial changes were strongly correlated with clinical improvements. Specifically, Haemophilus_D , Streptococcus , and Veillonella were most closely associated with clinical phenotypes of patients. Cross-study validation confirmed that the increase in Streptococcus , Akkermansia , Haemophilus_D , and Veillonella represents a conserved microbial signature of metabolic improvement following SG. These findings demonstrate that SG induced beneficial metabolic and inflammatory changes are closely linked to a significant restructuring of the gut microbiome, identifying specific bacterial taxa as potential therapeutic targets and providing new insights for the treatment of refractory obesity.