Fecal steroids and colorectal cancer

Owen, Robert W.; Dodo, Motoaki; Thompson, Mark J.; Hill, Michael J.

doi:10.1080/01635588709513914

Cited by 62 publications

(22 citation statements)

References 24 publications

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“…High concentrations of faecal bile acids have also been associated with the development of colon cancer, and the lithocholic acidadeoxycholic acid ratio has been reported to be increased in patients with colon cancer compared to controls (Owen et al, 1987). Ingestion of L. acidophilus for 6 weeks have been demonstrated to lower concentrations of total bile acid and deoxycholic acid (Lidbeck et al, 1991), although the changes were not signi®cant.…”

Section: Prevention Of Colonic Cancermentioning

confidence: 99%

Lactic acid bacteria and the human gastrointestinal tract

1999

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Objective: This review summarises the effects of lactic acid bacteria on lactose malabsorption, bacterialaviral or antibiotic associated diarrhoea, and describes the impact of lactic acid bacteria on cancer and the fermentative products in the colon. Results: Eight studies (including 78 patients) demonstrated that lactase de®cient subjects absorbed lactose in yogurt better than lactose in milk, while two studies (25 patients) did not support this. Two studies (22 patients) showed that unfermented acidophilus milk was absorbed better than milk, while six studies (68 patients) found no signi®cant differences. Addition of lactose hydrolysing enzyme, lactase, to milk improved lactose malabsorption in seven studies (131 lactose malabsorbers), while one study (10 malabsorbers) demonstrated no improvement. Lactic acid bacteria alleviated travellers' diarrhoea in one study (94 individuals) while a study including 756 individuals was borderline statistically signi®cant. One study (50 individuals) did not ®nd an effect of lactic acid bacteria on travellers' diarrhoea. Six studies (404 infants) demonstrated a signi®cant effect of lactic acid bacteria on infant diarrhoea, while one study (40 infants) did not. Lactic acid bacteria moderated antibiotic associated diarrhoea in three studies (66 individuals), while two studies (117 individuals) were insigni®cant. Conclusions: Lactase de®cient subjects bene®t from a better lactose absorption after ingestion of yoghurt compared with milk and from milk added lactase, whereas ingestion of unfermented acidophilus milk does not seem to improve lactose absorption. The majority of studies support that lactic acid bacteria alleviate bacterialaviral induced diarrhoea, especially in infants, while the effect on antibiotic associated diarrhoea is less clear.Experimental studies indicate an effect of lactic bacteria on human cell cancer lines, but clinical evidence is lacking. A`stabilising' effect of lactic acid bacteria on the colonic¯ora has not been documented.

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Section: Prevention Of Colonic Cancermentioning

confidence: 99%

Lactic acid bacteria and the human gastrointestinal tract

1999

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“…At higher concentrations, LCA forms DNA adducts and inhibits DNA repair enzymes [117][118][119]. High colonic levels of LCA are implicated as a factor in colorectal cancer [120], and LCA promotes colon cancer in animal models [121].…”

Section: Bile Saltsmentioning

confidence: 99%

Evolution and Function of the NR1I Nuclear Hormone Receptor Subfamily (VDR, PXR, and CAR) with Respect to Metabolism of Xenobiotics and Endogenous Compounds

Reschly¹,

Krasowski²

2006

CDM

126

130

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The NR1I subfamily of nuclear hormone receptors includes the 1,25-(OH) 2 -vitamin D 3 receptor (VDR; NR1I1), pregnane X receptor (PXR; NR1I2), and constitutive androstane receptor (CAR; NR1I3). PXR and VDR are found in diverse vertebrates from fish to mammals while CAR is restricted to mammals. Current evidence suggests that the CAR gene arose from a duplication of an ancestral PXR gene, and that PXR and VDR arose from duplication of an ancestral gene, represented now by a single gene in the invertebrate Ciona intestinalis. Aside from the high-affinity effects of 1,25-(OH) 2 -vitamin D 3 on VDRs, the NR1I subfamily members are functionally united by the ability to bind potentially toxic endogenous compounds with low affinity and initiate changes in gene expression that lead to enhanced metabolism and elimination (e.g., induction of cytochrome P450 3A4 expression in humans). The detoxification role of VDR seems limited to sensing high concentrations of certain toxic bile salts, such as lithocholic acid, whereas PXR and CAR have the ability to recognize structurally diverse compounds. PXR and CAR show the highest degree of crossspecies variation in the ligand-binding domain of the entire vertebrate nuclear hormone receptor superfamily, suggesting adaptation to species-specific ligands. This review examines the insights that phylogenetic and experimental studies provide into the function of VDR, PXR, and CAR, and how the functions of these receptors have expanded to evolutionary advantage in humans and other animals.

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“…Administration of LCA and its conjugates in rodents causes histologic liver damage and other pathological changes (1,2). Elevated levels of LCA have also been correlated with increased incidence of colorectal cancer (3,4).…”

mentioning

confidence: 99%

Regulation of a xenobiotic sulfonation cascade by nuclear pregnane X receptor (PXR)

Sonoda

Xie

Rosenfeld

et al. 2002

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

259

194

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The nuclear receptor PXR (pregnane X receptor) protects the body from hepatotoxicity of secondary bile acids such as lithocholic acid (LCA) by inducing expression of the hydroxylating cytochrome P450 enzyme CYP3A and promoting detoxification. We found that activation of PXR also increases the activity and gene expression of the phase II conjugating enzyme dehydroepiandrosterone sulfotransferase (STD) known to sulfate LCA to facilitate its elimination. This activation is direct and appears to extend to other xenobiotic sulfotransferases as well as to 3-phosphoadenosine 5-phosphosulfate synthetase 2 (PAPSS2), an enzyme that generates the donor cofactor for the reaction. Because sulfation plays an important role in the metabolism of many xenobiotics, prescription drugs, and toxins, we propose that PXR serves as a master regulator of the phase I and II responses to facilitate rapid and efficient detoxification and elimination of foreign chemicals.

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Fecal steroids and colorectal cancer

Cited by 62 publications

References 24 publications

Lactic acid bacteria and the human gastrointestinal tract

Lactic acid bacteria and the human gastrointestinal tract

Evolution and Function of the NR1I Nuclear Hormone Receptor Subfamily (VDR, PXR, and CAR) with Respect to Metabolism of Xenobiotics and Endogenous Compounds

Regulation of a xenobiotic sulfonation cascade by nuclear pregnane X receptor (PXR)

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