Plant-based diets, gut microbiota, blood metabolome, and risk of colorectal, liver, and pancreatic cancers: results from a large prospective cohort study of predominantly low-income Americans

Fangcheng Yuan; Lei Wang; Sang M Nguyen; Xiao-Ou Shu; Martha J Shrubsole; Wanqing Wen; Qiuyin Cai; Danxia Yu; Wei Zheng

doi:10.1016/j.ajcnut.2025.101135

Plant-based diets, gut microbiota, blood metabolome, and risk of colorectal, liver, and pancreatic cancers: results from a large prospective cohort study of predominantly low-income Americans

Am J Clin Nutr. 2025 Dec 12:101135. doi: 10.1016/j.ajcnut.2025.101135. Online ahead of print.

Authors

Fangcheng Yuan¹, Lei Wang¹, Sang M Nguyen¹, Xiao-Ou Shu¹, Martha J Shrubsole¹, Wanqing Wen¹, Qiuyin Cai¹, Danxia Yu¹, Wei Zheng²

Affiliations

¹ From the Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, United States.
² From the Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, United States. Electronic address: wei.zheng@vanderbilt.edu.

PMID: 41391639
DOI: 10.1016/j.ajcnut.2025.101135

Abstract

Background: Plant-based diets have been advertised for environmental and health benefits. Their effects on cancer risk, gut microbial, and blood metabolomic profiles remain unclear.

Objectives: We investigated plant-based diets in relation to cancer incidence as well as gut microbial composition and blood metabolites in the Southern Community Cohort Study.

Methods: Included in the analysis were 71,533 participants. Habitual dietary intake assessed at baseline (2002-2009) was used to derive the overall plant-based diet index (PDI), healthy plant-based diet index (hPDI), and unhealthy plant-based diet index (uPDI). Incident cancer cases were ascertained via linkage to state cancer registries and the National Death Index. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazards models after adjusting for potential confounders. We examined associations of the 3 indices with gut microbiota and blood metabolites using fecal metagenomic and blood metabolomic data from 2 subsets of 417 and 1581 participants, respectively.

Results: During a median follow-up time of 11.6 y, 783, 316, and 295 incident colorectal, liver, and pancreatic cancer cases were identified. High hPDI was related to a lower liver cancer risk (HR: 0.67, 95% CI: 0.45, 0.99 comparing extreme quartiles, P-trend = 0.03). No apparent association was observed for colorectal cancer (CRC) in the whole cohort. However, among 49,132 CRC screening-naïve participants at baseline, PDI was inversely associated (HR: 0.74, 95% CI: 0.58, 0.96, P-trend = 0.01), whereas uPDI was positively associated (HR: 1.39, 95% CI: 1.06, 1.82, P-trend = 0.02) with CRC risk. No index was associated with pancreatic cancer. These diet indices were associated with microbial taxa and blood metabolites that have been implicated in the tumorigenesis of the colorectum and liver.

Conclusions: A diet high in healthy plant foods and low in animal foods was inversely associated with liver cancer risk and with CRC risk among screening-naïve participants. These associations may be partly mediated through gut microbiota and systemic metabolism.

Keywords: blood metabolome; digestive system cancer; epidemiology; gut microbiota; health disparities; plant-based diets.