Smoking-related gut microbiota alteration is associated with obesity and obesity-related diseases: results from two cohorts with sibling comparison analysesOriginal paper
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease, four years before the first published case study.
Read MoreWhat was studied?
This study investigated the smoking paradox, in which smokers tend to have lower body mass index but higher risk of obesity-related disease, through the lens of the gut microbiota. Researchers used 16S rRNA sequencing to identify smoking-related microbial genera and built a smoking-related microbiota index (SMI). They then tested whether SMI was associated with obesity indices and with incident obesity-related diseases, including analyses designed to control for shared familial and environmental confounders.
Who was studied?
The analysis drew on 4000 male participants from two cohorts, the WELL-China cohort and the Lanxi cohort. Obesity indices were derived using dual-energy X-ray absorptiometry (DEXA) scans in these participants. A subset of participants with siblings was used for sibling comparison analyses via a between-within (BW) model, allowing the researchers to account for unmeasured familial confounding.
What were the most important findings?
The smoking-related microbiota index (SMI) was positively associated with BMI and other DEXA-derived obesity indices. Higher SMI was also linked to greater risk of incident obesity-related disease, with hazard ratios of 1.97 for diabetes, 1.31 for major adverse cardiovascular events, and 1.70 for obesity-related cancers. These associations held up in sibling comparison analyses, which help rule out shared family environment or genetics as the explanation.
What are the greatest implications of this study?
The findings suggest that smoking-associated shifts in gut microbiota may help explain why smokers face elevated cardiometabolic and cancer risk despite often having lower BMI. This reframes the smoking-obesity paradox as partly a microbiome-mediated phenomenon rather than a purely anthropometric one. The sibling comparison design strengthens confidence that the microbiota signal is not simply a marker of shared family background. These results point to the gut microbiota as a potential target or biomarker for assessing metabolic and disease risk in people who smoke.