The sulfur microbial diet (SMD), characterized by high intake of processed meats, alcohol, and artificially sweetened beverages, has been suggested to be associated with gut microbial dysbiosis by influencing sulfur-reducing bacterial activity. These microbial changes may be associated with altered production of hydrogen sulfide (H₂S) and lipopolysaccharide (LPS), potentially contributing to systemic inflammation, metabolic disorders, alterations in gut-related biomarkers such as nerve growth factor (NGF). However, the metabolic and neuroimmune consequences of this dietary pattern in overweight and obese individuals remain unclear. In the current study we aimed to examine the association between adherence to the SMD and metabolic risk factors, gut-brain axis biomarkers (LPS and NGF), and adiposity indicators in a population of overweight and obese adults. In this cross-sectional study, 633 overweight and obese adults (BMI ≥ 25 kg/m²) aged 20-60 years were recruited from outpatient nutrition clinics. Dietary intake was assessed using a previously validated food frequency questionnaire, and SMD scores were calculated based on the intake of eight food groups included in the original SMD scoring methodology. Participants were categorized into quartiles of SMD adherence. Anthropometric measures and fasting blood samples were collected to assess metabolic markers, LPS, and NGF. Participants with higher SMD scores had significantly higher total cholesterol levels (adjusted P = 0.028), while adjusted comparisons showed a significant difference in circulating NGF levels between SMD quartiles (adjusted P = 0.047). LPS concentrations differed significantly across SMD quartiles after multivariable adjustment (adjusted P = 0.037), with a significant linear trend across quartiles (P for trend = 0.011). No significant differences were observed for fasting glucose, insulin, triglycerides, or blood pressure. Higher adherence to the sulfur microbial diet was associated with differences in total cholesterol, NGF, and LPS concentrations among adults with overweight and obesity. These findings suggest that greater adherence to this dietary pattern may be accompanied by alterations in metabolic and gut-related biomarkers. Given the cross-sectional design of the study, causal relationships cannot be inferred, and prospective studies are needed to confirm these associations.
