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The FISHGASTRO study: gene expression profiles in human colonic biopsies following a 6 month fish intervention

ABSTRACT: Gene expression profiles in human colonic biopsies following a 6 month fish intervention highlights the importance of interactions between diet and mucosal immunoregulation: the FISHGASTRO study. Data from population based studies indicate a strong association between risk of colon cancer and lifestyle, including diet. There is an increasing body of evidence to suggest that high fish intake may be protective. N-3 polyunsaturated fatty acids, highly abundant in oily fish such as salmon, have been the focus of attention and several molecular mechanisms have been proposed to explain their anti-neoplastic activity. Other nutrients such as vitamin D and selenium (also found in lean fish) are well recognised as protective agents against many cancers, including colon cancer. The FISHGASTRO human intervention study was carried out to assess the impact of two types of fish, salmon and cod, on already established markers of gastrointestinal health and to search for novel biomarkers of cancer risk based on post-genomic technology. Keywords: Expression profiling by array

ORGANISM(S): Homo sapiens

PROVIDER: GSE15284 | GEO | 2025/02/01

REPOSITORIES: GEO

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Project description:Red meat consumption is associated with an increased colon cancer risk. Heme, present in red meat, injures the colon surface epithelium by luminal cytotoxicity and reactive oxygen species. This surface injury is overcompensated by hyperproliferation and hyperplasia of crypt cells. Transcriptome analysis of mucosa of heme-fed mice showed, besides stress- and proliferation-related genes, many upregulated lipid metabolism-related PPARM-NM-1 target genes. The aim of this study was to investigate the role of PPARM-NM-1 in heme-induced hyperproliferation and hyperplasia. Male PPARM-NM-1 KO and WT mice received a purified diet with or without heme. As PPARM-NM-1 is proposed to protect against oxidative stress and lipid peroxidation, we hypothesized that the absence of PPARM-NM-1 leads to more surface injury and crypt hyperproliferation in the colon upon heme-feeding. Heme induced luminal cytotoxicity and lipid peroxidation and colonic hyperproliferation and hyperplasia to the same extent in WT and KO mice. Transcriptome analysis of colonic mucosa confirmed similar heme-induced hyperproliferation in WT and KO mice. Stainings for alkaline phosphatase activity and expression levels of Vanin-1 and Nrf2-targets indicated a compromised antioxidant defense in heme-fed KO mice. Our results suggest that the protective role of PPARM-NM-1 in antioxidant defense involves the Nrf2-inhibitor Fosl1, which is upregulated by heme in PPARM-NM-1 KO mice. We conclude that PPARM-NM-1 plays a protective role in colon against oxidative stress, but PPARM-NM-1 does not mediate heme-induced hyperproliferation. This implies that oxidative stress of surface cells is not the main determinant of heme-induced hyperproliferation and hyperplasia. Wild type and peroxisome proliferator-activated receptor alpha (PPARM-NM-1) knockout mice were fed a Westernized high fat diet, or the same diet supplemented with 0.5 M-BM-5mol heme/g diet. After 14 days of intervention, mice were killed and gene expression was profiled in colon.

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The FISHGASTRO study: gene expression profiles in human colonic biopsies following a 6 month fish intervention

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