biostudies-literatureDuan Y"Pioneer" and "Leading Goose" R&D Program of Zhejiangthe National Key R&D Program of China146https://www.ebi.ac.uk/biostudies/studies/S-EPMC11892230biostudies-literatureUnknown23(1)<h4>Background</h4>Individuals who smoke tend to have a lower body mass index (BMI) but face an increased risk of obesity-related diseases. This study investigates this paradox from the perspective of gut microbiota.<h4>Methods</h4>We conducted microbiome analyses to identify smoking-related microbial genera and created a smoking-related microbiota index (SMI) using 16S rRNA sequencing data from 4000 male participants in WELL-China cohort and Lanxi cohort. We employed logistic regression to explore the association between SMI and obesity indices derived from dual-energy X-ray absorptiometry. Cox regression analyses were conducted to explore the association of SMI with incident of obesity-related diseases. To further control for unmeasured familial confounders, sibling comparison analyses wBMC medicineSmoking-related gut microbiota alteration is associated with obesity and obesity-related diseases: results from two cohorts with sibling comparison analyses.PMC11892230Grant No. 2024C03180Grant No. 2022YFC2705300Grant No. 2022YFC2705303Xu NYu MMyers ALu YXu CZheng WDelzell EWu YHGong WHsing AWHe WWang WWang XZhong JChu LDuan YZhu SfalseSmoking-related gut microbiota alteration is associated with obesity and obesity-related diseases: results from two cohorts with sibling comparison analyses.<h4>Background</h4>Individuals who smoke tend to have a lower body mass index (BMI) but face an increased risk of obesity-related diseases. This study investigates this paradox from the perspective of gut microbiota.<h4>Methods</h4>We conducted microbiome analyses to identify smoking-related microbial genera and created a smoking-related microbiota index (SMI) using 16S rRNA sequencing data from 4000 male participants in WELL-China cohort and Lanxi cohort. We employed logistic regression to explore the association between SMI and obesity indices derived from dual-energy X-ray absorptiometry. Cox regression analyses were conducted to explore the association of SMI with incident of obesity-related diseases. To further control for unmeasured familial confounders, sibling comparison analyses w2025-01-01T00:00:00Z2025 Mar2025-04-22T11:08:57.894Z2025-04-05T23:53:49.947ZS-EPMC118922304005917010.1186/s12916-025-03969-4