Scientists studied diet and lung cancer in 95,612 adults. One eating pattern stood out

Could the foods that shape sulfur-metabolizing gut bacteria offer new clues about lung cancer? Researchers examined dietary patterns and long-term health outcomes in nearly 96,000 American adults.

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A recent study in the Nutrition Journal examined whether a sulfur microbial diet (SMD) score is associated with lung cancer incidence and lung cancer-related mortality in a large U.S. prospective cohort.

Role of Diet and the Microbiome in Lung Cancer Risk

Lung cancer remains the leading cause of cancer mortality globally, with a five-year survival rate near 25% in the United States. While smoking is the predominant risk factor, incidence in never-smokers and heterogeneous risk among ever-smokers show the importance of identifying additional modifiable risk factors.

Among these, habitual diet has gained attention. Prospective analyses in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial have linked higher dietary quality to reduced lung cancer risk. However, the researchers have not explored the association between microbiome-linked dietary patterns and lung cancer.

Diet, a major determinant of gut microbial composition and function, may influence lung cancer risk via the gut-lung axis, in which the intestinal microbiota and their metabolites affect systemic immunity and airway inflammation. Sulfur-metabolizing bacteria, such as Bilophila wadsworthia and Desulfovibrionaceae, reduce dietary sulfur-containing substrates to hydrogen sulfide (H₂S), which at high concentrations may impair epithelial barrier function, cause DNA damage, and increase systemic inflammation.

Because large cohorts lack stool sequencing data, a food-based sulfur microbial diet (SMD) score was developed as a microbiome-related dietary proxy using 25 food-group components and sparse canonical correlation analysis. Higher SMD scores have been linked to increased risk of colorectal cancer, early-onset colorectal cancer precursors, and esophageal squamous cell carcinoma in the PLCO cohort.

Higher SMD scores have also been linked to increased all-cause and cancer-specific mortality, though site-specific effects are not well defined. Lung cancer shares pathogenic mechanisms with SMD-associated gastrointestinal cancers, such as epithelial injury, inflammation, and host-microbial interactions.

Examining the Associations between SMD score and lung cancer incidence and mortality

The study included participants from the PLCO Cancer Screening Trial, which enrolled approximately 155,000 U.S. adults aged 55–74 years from 1993 to 2001 across 10 screening centers. Lung cancer incidence was monitored through December 2009, and mortality through December 2018. After applying eligibility criteria, the final analytic cohort included 95,612 participants.

The researchers derived the SMD score from dietary data collected via a 124-item questionnaire, administered at a median of 3 years post-randomization. This score included 25 standardized, weighted food group components, with higher values reflecting closer adherence to the SMD dietary pattern. Because direct microbiome or sulfur-metabolite measurements were unavailable, the SMD score served as a dietary proxy and was analyzed both in quintiles and as a continuous variable.

Lung cancer cases and subtypes were identified through annual updates and confirmed by medical records. Deaths were identified from these updates and National Death Index linkage, with lung cancer deaths confirmed through blinded review. Follow-up began at questionnaire completion and continued until lung cancer diagnosis or December 2009 for incidence, and until lung cancer-related death or December 2018 for mortality, with deaths from other causes treated as censored events in the primary models.

Lung cancer mortality was analyzed as the risk of fatal lung cancer, not survival after diagnosis. The researchers estimated hazard ratios (HRs) for both incidence and mortality using three sequentially adjusted Cox models that accounted for demographic, health, lifestyle, and dietary covariates.

Higher SMD Score Linked to Increased Lung Cancer Incidence and Mortality

Among the 95,612 participants (mean age 65.5 years, 52 percent women), SMD score quintiles reflected a weighted combination of 25 food groups. Participants in the highest-scoring quintile (Q5) generally consumed more red and processed meats, French fries, and high-fat dairy, and fewer fruits, yellow vegetables, and whole grains than those in the lowest-scoring quintile (Q1). Compared to Q1, individuals in Q5 were younger, more often male, had higher body mass index (BMI) and higher rates of smoking, diabetes, and hypertension, and consumed less total energy and were less likely to use supplemental beta-carotene.

Over 844,773 person-years of incidence follow-up, the study observed 1,561 lung cancer cases and, across 1,443,711 person-years of mortality follow-up, 2,109 lung cancer deaths. Mortality tracking continued nine years beyond incidence tracking, explaining why deaths outnumbered the recorded cases. Lung cancer incidence rates rose from 1.20 per 1,000 person-years in Q1 to 3.03 per 1,000 in Q5, with mortality rates showing a similar increase across quintiles.

After adjusting for confounders, those in Q5 had a 23% higher estimated hazard of developing lung cancer and a 19% higher estimated hazard of dying from lung cancer compared to Q1. These adjusted differences were substantially smaller than the crude rates suggested because the models accounted for smoking and other participant characteristics. Each standard deviation increase in SMD score was associated with about a 6% higher risk of lung cancer and a 5% higher risk of mortality, but neither continuous association reached conventional statistical significance. The findings remained consistent in most sensitivity analyses, but weakened in competing-risk analyses, where the trend tests were no longer statistically significant.

The mortality association was stronger among participants with more than 20 pack-years of smoking, and this interaction remained significant after correction for multiple comparisons. No significant interaction was confirmed for lung cancer incidence or the other factors assessed. After further adjusting for overall diet quality, the associations decreased and were no longer statistically significant.

When considering histologic subtypes, the association between higher SMD score and lung cancer risk was strongest for squamous cell and small cell carcinomas, while no significant association was detected for adenocarcinoma. These subtype findings were exploratory.

No single food component drove the SMD-lung cancer association, and only yellow vegetable intake was significantly associated with lower lung cancer mortality after multiple-testing correction. Coffee intake showed a nominal association with incidence, but not after correction.

Conclusions

A higher SMD score was associated with modestly higher risks of lung cancer incidence and mortality, especially for lung cancer deaths among heavy smokers and for squamous or small cell lung cancer incidence. These exploratory subgroup findings require confirmation, particularly because smoking exposure may have influenced the results. The associations weakened after accounting for overall diet quality and competing causes of death, and the study could not establish an independent sulfur-related microbial mechanism.

The authors noted several limitations, including the study's observational design, which limits causal inference, and residual confounding from incompletely measured smoking exposure. The absence of repeated dietary assessments may have introduced exposure misclassification, while limited cohort diversity restricted the generalizability of the findings. The researchers did not measure gut microbes, sulfur metabolites, or hydrogen sulfide, so they could not directly test the proposed microbial pathways.

Future research should include more diverse populations with repeated dietary assessments and direct microbial and sulfur-metabolite measurements to better elucidate the role of sulfur-metabolizing dietary patterns and related microbial pathways in lung cancer risk.

Source:

Journal reference:

• Luo, Y., Xiao, Y., Yang, J., et al. (2026). Association of sulfur microbial diet with lung cancer incidence and lung cancer-related mortality in 95,612 American adults: a prospective cohort study from the PLCO trial. Nutrition Journal. DOI:10.1186/s12937-026-01406-7, https://link.springer.com/article/10.1186/s12937-026-01406-7