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Randomized Controlled Trial
. 2022 Oct 1;13(10):e00533.
doi: 10.14309/ctg.0000000000000533.

Circulating Bile Acids and Adenoma Recurrence in the Context of Adherence to a High-Fiber, High-Fruit and Vegetable, and Low-Fat Dietary Intervention

Affiliations
Randomized Controlled Trial

Circulating Bile Acids and Adenoma Recurrence in the Context of Adherence to a High-Fiber, High-Fruit and Vegetable, and Low-Fat Dietary Intervention

Doratha A Byrd et al. Clin Transl Gastroenterol. .

Abstract

Introduction: Diet may affect bile acid (BA) metabolism and signaling. In turn, BA concentrations may be associated with cancer risk. We investigated (i) associations of BA concentrations with adenoma recurrence and (ii) the effect of a high-fiber, high-fruit and vegetable, and low-fat dietary intervention on serum BA concentrations.

Methods: The Polyp Prevention Trial is a 4-year randomized, controlled trial that investigated the effect of a high-fiber, high-fruit and vegetable, and low-fat diet on colorectal adenoma recurrence. Among 170 participants who reported adhering to the intervention and 198 comparable control arm participants, we measured 15 BAs in baseline, year 2, and year 3 serum using targeted, quantitative liquid chromatography-tandem mass spectrometry. We estimated associations of BAs with adenoma recurrence using multivariable logistic regression and the effect of the dietary intervention on BA concentrations using repeated-measures linear mixed-effects models. In a subset (N = 65), we investigated associations of BAs with 16S rRNA gene sequenced rectal tissue microbiome characteristics.

Results: Baseline total BA concentrations were positively associated with adenoma recurrence (odds ratio Q3 vs Q1 = 2.17; 95% confidence interval = 1.19-4.04; Ptrend = 0.03). Although we found no effect of the dietary intervention on BA concentrations, pretrial dietary fiber intake was inversely associated with total baseline BAs (Spearman = -0.15; PFDR = 0.02). BA concentrations were associated with potential colorectal neoplasm-related microbiome features (lower alpha diversity and higher Bacteroides abundance).

Discussion: Baseline circulating BAs were positively associated with adenoma recurrence. Although the dietary intervention did not modify BA concentrations, long-term fiber intake may be associated with lower concentrations of BAs that are associated with higher risk of adenoma recurrence.

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Conflict of interest statement

Guarantor of the article: Doratha A. Byrd, PhD, MPH.

Specific author contributions: D.A.B., R.S., and E.L. conceptualized the study, analyzed the data, and drafted/edited the manuscript. M.G. and P.A. assisted with statistical analysis planning, data processing and analysis, and manuscript editing. G.M., J.N.S., E.V., and N.D.F. contributed to study design and manuscript editing. S.H. assisted with manuscript editing.

Financial support: This study was supported by funding from the Intramural Research Program of the National Cancer Institute at the National Institutes of Health. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations implying endorsement by the US Government.

Potential competing interests: None to report.

Patient consent: Written informed consent was obtained from all participants.

Data availability: Data are available upon reasonable request. The microbiome sequencing and corresponding metadata that support the findings of this study are openly available in the National Center for Biotechnology (NCBI) Sequence Read Archive (http://www.ncbi.nlm.nih.gov/bioproject/PRJNA810087; bioproject ID PRJNA810087). This analysis was not preregistered in an independent, institutional registry.

Figures

Figure 1.
Figure 1.
Study design and data included at each time point for the analysis of effects of the high-fiber, high-fruit and vegetable, and low-fat dietary intervention on circulating BAs and of BAs with adenoma recurrence in the Polyp Prevention Trial, 1991–1998. BA, bile acid.

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