Colonic mucosal and exfoliome transcriptomic profiling and fecal microbiome response to a flaxseed lignan extract intervention in humans

• Published in: The American journal of clinical nutrition 2019-08, Vol.110 (2), p.377-390
• Main Authors: Lampe, Johanna W, Kim, Eunji, Levy, Lisa, Davidson, Laurie A, Goldsby, Jennifer S, Miles, Fayth L, Navarro, Sandi L, Randolph, Timothy W, Zhao, Ni, Ivanov, Ivan, Kaz, Andrew M, Damman, Christopher, Hockenbery, David M, Hullar, Meredith AJ, Chapkin, Robert S
• Format: Article
• Language: English
• Subjects: Adult; Animal models; Biopsy; Cancer; Colon; Colon - drug effects; Colorectal carcinoma; Community composition; Consortia; Cross-Over Studies; Double-Blind Method; enterolactone; Excretion; fecal microbiome; Fecal microflora; Feces; Feces - microbiology; Female; Flax - chemistry; Food plants; Functional analysis; Gas chromatography; Gastrointestinal Microbiome; Gene expression; Gene Expression Profiling; Gene Expression Regulation - drug effects; Genes; Growth factors; Health risks; human intervention; Humans; Inflammation; Interleukin 10; Intestinal microflora; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; lignan; Lignans; Lignans - chemistry; Male; Mass spectrometry; Mass spectroscopy; Microbiomes; Microorganisms; Mucosa; Original Research Communications; Plant Extracts - chemistry; Plant Extracts - pharmacology; Regulators; Ribonucleic acid; RNA; rRNA 16S; secoisolariciresinol; Statistical analysis; Statistical methods; Transforming growth factor; Transforming growth factor-b; Tumorigenesis; Urine
• ISSN: 0002-9165; 1938-3207
• DOI: 10.1093/ajcn/nqy325

Microbial metabolism of lignans from high-fiber plant foods produces bioactive enterolignans, such as enterolactone (ENL) and enterodiol (END). Enterolignan exposure influences cellular pathways important to cancer risk and is associated with reduced colon tumorigenesis in animal models and lower colorectal cancer risk in humans. The aim of this study was to test the effects of a flaxseed lignan supplement (50 mg secoisolariciresinol diglucoside/d) compared with placebo on host gene expression in colon biopsies and exfoliated colonocyte RNA in feces and fecal microbial community composition, and to compare responses in relation to ENL excretion. We conducted a 2-period randomized, crossover intervention in 42 healthy men and women (20–45 y). We used RNA-seq to measure differentially expressed (DE) genes in colonic mucosa and fecal exfoliated cells through the use of edgeR and functional analysis with Ingenuity Pathway Analysis. We used 16S ribosomal RNA gene (V1–V3) analysis to characterize the fecal microbiome, and measured END and ENL in 24-h urine samples by gas chromatography–mass spectrometry. We detected 32 DE genes (false discovery rate