Effect of pH on bile salt degradation by mixed fecal cultures

Macdonald, Ian A.; Singh, Gurmit; Mahony, D. E.; Meier, C. Elizabeth

doi:10.1016/0039-128x(78)90009-0

Cited by 78 publications

(32 citation statements)

References 16 publications

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“…Further, the decreased luminal pH induced by SCFA production may stimulate mineral absorption through increased mineral solubility (3 1,32). A lower luminal pH may also reduce secondary bile acid formation (33). Further, SCFAs have been shown to influence the gastrointestinal motility by mechanisms that are not yet fully understood (34).…”

Section: Nutritional Implications Of Short-chain Fatty Acidsmentioning

confidence: 99%

Short-chain fatty acid formation at fermentation of indigestible carbohydrates

2001

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Short chain fatty acids (SCFAs; acetic, propionic and butyric acid) are formed during bacterial fermentation of carbohydrates in the colon. The interest in SCFA production is related to an increasing body of knowledge of the physiological effects of these acids. SCFAs are important anions in the colonic lumen and serve locally as nutrients for the mucosa cells, stimulating mucosal proliferation and blood flow. Especially butyric acid has been cmphazised. It is the main energy substrate for the colonocytes and has been suggested to play a role in the prevention and treatment of diseases of the colonic mucosa, such as distal ulcerative colitis and cancer. SCFA production decreases the luminal pH, and may thereby stimulate mineral absorption and reduce secondary bile acid formation in the colon. Colonic generation of SCFAs has also been related to systematic and metabolic effects, e.g. SCFAs may influence the motility along the gastrointestinal tract and propionic acid has been suggested to inhibit the cholesterol synthesis from acetic acid in the liver. The SCFAformed at fermentation is quantitatively and qualitatively influenced by the type and amount of carbohydrate substrate. Further, certain combinations of carbohydrates may have synergistic effects on the SCFA pattern and may also shift the site of fermentation. This opens possibilities to design foods with tailored features regarding SCFA release in the human colon with potential health implications. There is apotential that in the future it will be possible to control SCFAproduction in the colon regarding pattern and place for release.

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Section: Nutritional Implications Of Short-chain Fatty Acidsmentioning

confidence: 99%

Short-chain fatty acid formation at fermentation of indigestible carbohydrates

2001

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“…In vivo both are present in the colon and may influence each other's actions directly or indirectly. For example, butyrate is known to modify colonic pH and inhibit the colonic bacteria responsible for the production of bile acids (MacDonald et al, 1978). We have shown previously that human adenoma cells, AA/C1, treated with physiological levels of bile acids showed increased proliferation (McMillan et al, 2000).…”

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Opposing effects of butyrate and bile acids on apoptosis of human colon adenoma cells: differential activation of PKC and MAP kinases

et al. 2003

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Butyrate, produced in the colon by fermentation of dietary fibre, induces apoptosis in colon adenoma and cancer cell lines, which may contribute to protection against colorectal cancer. However, butyrate is present in the colon along with other dietary factors, including unconjugated bile acids, which are tumour promoters. We have shown previously that the proapoptotic effects of butyrate on AA/C1 human adenoma cells were reduced in the presence of bile acids. To determine the cellular basis of this interaction, we examined the effects of butyrate and the secondary bile acid ursodeoxycholic acid (UDCA) on signalling pathways known to regulate apoptosis using AA/C1 cells. Butyrate activated PKC-d and p38 MAP (mitogen-activated protein) kinase, whereas UDCA activated PKC-a and p42/44 MAP kinase. Butyrate treatment also resulted in the caspase-3-mediated proteolysis of PKC-d. Butyrate-induced apoptosis was reduced by inhibitors of PKC-d (Rottlerin), p38 MAP kinase (SB202190) and caspase 3 (DEVD-fmk), whereas the proliferative/survival effects of UDCA were blocked by inhibitors of PKC-a (Gö 6976) and MEK 1 (PD98059). The effects of butyrate and bile acids are therefore mediated by the differential activation of signalling pathways that are known to regulate apoptosis.

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Section: Discussionmentioning

confidence: 99%

“…Longchain saturated fatty acids bind calcium more strongly than longchain unsaturated fatty acids (Cheng et al, 1949). A lower colonic pH results in less formation of DC from CA, while the activity of the bacterial enzyme 7a-dehydroxylase is inhibited in vitro at pHo6 (MacDonald et al, 1978).The positive relation between DC/CDC ratio and dietary fibre from sources other than fruits and vegetables can be explained by the latter being mainly derived from grains that contain wheat bran and resistant starch. These will lower the concentrations of BA in the intestine due to increased faecal wet weight (Cummings et al, 1978;Heijnen et al, 1998), and therefore lower the concentrations of BA returning to the liver.…”

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Serum bile acids and risk factors for colorectal cancer

2004

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The ratio of deoxycholic acid to chenodeoxycholic acid in the serum of 62 men was inversely related to body mass index and to saturated fat intake after adjustment for body mass index, smoking, and age conversely, this ratio was associated positively with the intake of fibre from grains. Bile acids (BA) are potential risk factors for colorectal cancer (CRC). A small prospective study suggests that a high ratio of deoxycholic acid (DC) to cholic acid (CA) in serum is associated with an increased incidence of CRC (Costarelli et al, 2002). Based on a complete model of BA metabolism (Chaplin, 1998), it can be argued that the ratio of unconjugated DC to unconjugated chenodeoxycholic acid (CDC) in serum, in short the DC/CDC ratio, is relevant to CRC. Unconjugated DC in serum is regarded as being a biomarker for habitual colonic exposure to the cancerpromoting DC (Bayerdörffer et al, 1993), because the unconjugated BA is absorbed in the colon. The DC/CDC ratio may be a marker with high intraindividual reproducibility, because the colonic absorption of unconjugated DC is nearly equal to that of unconjugated CDC (Mekhjian et al, 1979) and the hepatic clearance of DC from the portal vein is equal to that of CDC (Ahlberg et al, 1977). The only difference between the variation of DC and that of CDC can be attributed to the dehydroxylation of the primary bile acid cholic acid (CA) to the secondary bile acid DC. The formation of CA, unlike that of CDC, is regulated by the amount of BA returning to the liver. If less unconjugated DC is returned, relatively more CA will be formed and the DC/CDC ratio in serum will be higher.We studied the relation between the DC/CDC ratio in serum and such CRC-promoting (dietary) factors as intake of energy, saturated fat, fibre, calcium, smoking and body mass index (Giovannucci, 2003). MATERIALS AND METHODSNonfasting blood specimens were collected from 121 men and women in the range of 20 -60 years old, who participated in the validation study of the Dutch food frequency questionnaire for the European Prospective Investigation into Cancer and Nutrition (EPIC) . The samples of the 62 men, from which the blood was drawn more than 4 h after a meal, were selected for analysis of individual BA in the serum, as described before (Salemans et al, 1993). Only men were selected for logistic reasons. RESULTSThe characteristics of the study subjects, the dietary intakes of nutrients and the concentrations of total unconjugated BA in serum are shown in Table 1. Dietary fibre from sources other than fruits and vegetables was derived mainly from grains. In all, 25% of the men were current smokers.Saturated fat intake was inversely related to the log of serum DC/ CDC ratio univariately, as well as after adjustment for potential confounding factors like body mass index, smoking age and (Table 2). Also, calcium intake was inversely associated to the log of serum DC/CDC ratio in univariate analyses, but disappeared in the adjusted models. Conversely, for total dietary fibre, a positive relation was observed in t...

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Effect of pH on bile salt degradation by mixed fecal cultures

Cited by 78 publications

References 16 publications

Short-chain fatty acid formation at fermentation of indigestible carbohydrates

Short-chain fatty acid formation at fermentation of indigestible carbohydrates

Opposing effects of butyrate and bile acids on apoptosis of human colon adenoma cells: differential activation of PKC and MAP kinases

Serum bile acids and risk factors for colorectal cancer

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