The effects of short-chain fatty acids on colon epithelial proliferation and survival depend on the cellular phenotype

Comalada, Mònica; Bailón, Elvira; Haro, Oscar de; Lara-Villoslada, Federico; Xaus, Jordi; Zarzuelo, Antonio; Gálvez, Júlio

doi:10.1007/s00432-006-0092-x

Cited by 176 publications

(142 citation statements)

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“…As this SCFA did not induce apoptosis at the concentrations used in this study, we conclude that butyrate inhibits epithelial proliferation. Several in vitro studies support our finding that butyrate inhibits proliferation [33][34][35][36][37]. For example, butyrate inhibited the proliferation of non-confluent and sub-confluent HT-29 cells in a dosedependent manner (1-8 mM) [36].…”

Section: Discussionsupporting

confidence: 81%

“…Several in vitro studies support our finding that butyrate inhibits proliferation [33][34][35][36][37]. For example, butyrate inhibited the proliferation of non-confluent and sub-confluent HT-29 cells in a dosedependent manner (1-8 mM) [36]. Furthermore, Siavoshian et al demonstrated that the mechanism through which butyrate inhibits proliferation in HT-29 cells is exerted via the induction of cyclin D3, an inhibitor of cell cycle progression and p21, a stimulator of cell differentiation [33].…”

Section: Discussionsupporting

confidence: 80%

See 1 more Smart Citation

218 The Regulation of the Intestinal Mucin MUC2 Expression By Short Chain Fatty Acids: Implications for Epithelial Protection

Paassen¹,

Vincent²,

Puiman³

et al. 2009

Gastroenterology

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 80%

218 The Regulation of the Intestinal Mucin MUC2 Expression By Short Chain Fatty Acids: Implications for Epithelial Protection

Paassen¹,

Vincent²,

Puiman³

et al. 2009

Gastroenterology

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“…Butyrate, a histone deacetylase inhibitor that evokes pronounced transcriptional changes in different types of cultured epithelial cell lines (22)(23)(24)(25), is the preferred energy substrate for colonic enterocytes (26). While transcriptional changes caused by butyrate differ depending upon the cell lineage, state of cellular differentiation, and cellular energy status (23,24,27,28), in vitro and in vivo studies have shown that it affects expression of genes involved in proliferation, differentiation and apoptosis (25,28).…”

Section: Colonic Transcriptional Changes Evoked By E Rectale-b Thetmentioning

confidence: 99%

Characterizing a model human gut microbiota composed of members of its two dominant bacterial phyla

Mahowald¹,

Rey²,

Seedorf³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

602

441

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The adult human distal gut microbial community is typically dominated by 2 bacterial phyla (divisions), the Firmicutes and the Bacteroidetes. Little is known about the factors that govern the interactions between their members. Here, we examine the niches of representatives of both phyla in vivo. Finished genome sequences were generated from Eubacterium rectale and E. eligens, which belong to Clostridium Cluster XIVa, one of the most common gut Firmicute clades. Comparison of these and 25 other gut Firmicutes and Bacteroidetes indicated that the Firmicutes possess smaller genomes and a disproportionately smaller number of glycan-degrading enzymes. Germ-free mice were then colonized with E. rectale and/or a prominent human gut Bacteroidetes, Bacteroides thetaiotaomicron, followed by whole-genome transcriptional profiling, high-resolution proteomic analysis, and biochemical assays of microbial-microbial and microbial-host interactions. B. thetaiotaomicron adapts to E. rectale by up-regulating expression of a variety of polysaccharide utilization loci encoding numerous glycoside hydrolases, and by signaling the host to produce mucosal glycans that it, but not E. rectale, can access. E. rectale adapts to B. thetaiotaomicron by decreasing production of its glycan-degrading enzymes, increasing expression of selected amino acid and sugar transporters, and facilitating glycolysis by reducing levels of NADH, in part via generation of butyrate from acetate, which in turn is used by the gut epithelium. This simplified model of the human gut microbiota illustrates niche specialization and functional redundancy within members of its major bacterial phyla, and the importance of host glycans as a nutrient foundation that ensures ecosystem stability.human gut Firmicutes and Bacteroidetes ͉ carbohydrate metabolism ͉ gnotobiotic mice ͉ gut microbiome ͉ nutrient sharing

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“…Comalada et al (72) compared the effects of butyrate treatment on healthy fetal human colon cells and on HT-29 colorectal adenocarcinoma cells. Butyrate inhibited cell proliferation of the HT-29 cells but had no effect on the normal cells.…”

Section: The Effects Of Resistant Starch and Butyrate On Colonic Crypmentioning

confidence: 99%

Is resistant starch protective against colorectal cancer via modulation of the WNT signalling pathway?

2015

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Epidemiological and experimental evidence suggests that non-digestible carbohydrates (NDC) including resistant starch are protective against colorectal cancer. These anti-neoplastic effects are presumed to result from the production of the SCFA, butyrate, by colonic fermentation, which binds to the G-protein-coupled receptor GPR43 to regulate inflammation and other cancer-related processes. The WNT pathway is central to the maintenance of homeostasis within the large bowel through regulation of processes such as cell proliferation and migration and is frequently aberrantly hyperactivated in colorectal cancers. Abnormal WNT signalling can lead to irregular crypt cell proliferation that favours a hyperproliferative state. Butyrate has been shown to modulate the WNT pathway positively, affecting functional outcomes such as apoptosis and proliferation. Butyrate's ability to regulate gene expression results from epigenetic mechanisms, including its role as a histone deacetylase inhibitor and through modulating DNA methylation and the expression of microRNA. We conclude that genetic and epigenetic modulation of the WNT signalling pathway may be an important mechanism through which butyrate from fermentation of resistant starch and other NDC exert their chemoprotective effects.

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The effects of short-chain fatty acids on colon epithelial proliferation and survival depend on the cellular phenotype

Abstract: Although butyrate could exert antiproliferative effects in tumor progression, its production is safe and without consequences for the normal epithelium growth.

Cited by 176 publications

References 50 publications

218 The Regulation of the Intestinal Mucin MUC2 Expression By Short Chain Fatty Acids: Implications for Epithelial Protection

218 The Regulation of the Intestinal Mucin MUC2 Expression By Short Chain Fatty Acids: Implications for Epithelial Protection

Characterizing a model human gut microbiota composed of members of its two dominant bacterial phyla

Is resistant starch protective against colorectal cancer via modulation of the WNT signalling pathway?

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