Role of bile acids and metabolic activity of colonic bacteria in increased risk of colon cancer after cholecystectomy

Zuccato, Ettore; Venturi, Marco; Leo, Giuseppe Di; Colombo, Laura; Bértolo, Cristina; Doldi, S B; Mussini, E.

doi:10.1007/bf01316508

Cited by 89 publications

(67 citation statements)

References 46 publications

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“…The stool samples we used had been stored at Ϫ80°C for 10 to 20 years, and to our knowledge, there is no published literature regarding indole stability under such conditions. However, our stage 1 indole levels were consistent with values from control individuals in two earlier studies using freshly collected stool samples (43,44), although direct comparisons could not be made since stool samples were prepared, extracted, and tested by different techniques. Further, all of the stool samples we used were stored under the same conditions and the indole concentrations in samples from 1993 to 1998 were no different from those in samples from 1999 to 2004.…”

Section: Discussionsupporting

confidence: 48%

Fecal Indole as a Biomarker of Susceptibility to Cryptosporidium Infection

et al. 2016

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e Cryptosporidium causes significant diarrhea worldwide, especially among children and immunocompromised individuals, and no effective drug treatment is currently available for those who need it most. In this report, previous volunteer infectivity studies have been extended to examine the association between fecal indole and indole-producing (IP) gut microbiota on the outcome of a Cryptosporidium infection. Fecal indole concentrations (FICs) of 50 subjects and 19 taxa of common gut microbiota, including six IP taxa (11 subjects) were determined in stool samples collected before and after a challenge with Cryptosporidium oocysts. At the baseline, the mean FIC (؎ the standard deviation) was 1.66 ؎ 0.80 mM in those who became infected after a challenge versus 3.20 ؎ 1.23 mM in those who remained uninfected (P ‫؍‬ 0.0001). Only 11.1% of the subjects with a FIC of >2.5 mM became infected after a challenge versus 65.2% of the subjects with a FIC of <2.5 mM. In contrast, the FICs of infected subjects at the baseline or during diarrhea were not correlated with infection intensity or disease severity. The relative abundances (percent) of Escherichia coli, Bacillus spp., and Clostridium spp. were greater >2.5-fold in volunteers with a baseline FIC of >2.5 mM, while those of Bacteroides pyogenes, B. fragilis, and Akkermansia muciniphila were greater in those with a baseline FIC of <2.5 mM. These data indicate that some IP bacteria, or perhaps indole alone, can influence the ability of Cryptosporidium to establish an infection. Thus, preexisting indole levels in the gut join the oocyst dose and immune status as important factors that determine the outcome of Cryptosporidium exposure.

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Section: Discussionsupporting

confidence: 48%

Fecal Indole as a Biomarker of Susceptibility to Cryptosporidium Infection

et al. 2016

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“…Few studies have reported indole concentrations in the stools of healthy adults. Gas chromatographic analysis of indole and 3-methylindole (skatole) from the fecal samples of 84 patients with colorectal cancers, 20 postsurgical cholecystectomy patients, and 15 healthy control patients reported concentrations in the 5-to 156-g/g range for the two molecules (29,30). These values are roughly consistent with what we found but cannot be compared directly since the data were expressed per gram (dry weight) of feces.…”

Section: Discussionsupporting

confidence: 81%

A Rapid and Specific Method for the Detection of Indole in Complex Biological Samples

Darkoh

Chappell

Gonzales

et al. 2015

Appl Environ Microbiol

116

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bIndole, a bacterial product of tryptophan degradation, has a variety of important applications in the pharmaceutical industry and is a biomarker in biological and clinical specimens. Yet, specific assays to quantitate indole are complex and require expensive equipment and a high level of training. Thus, indole in biological samples is often estimated using the simple and rapid Kovács assay, which nonspecifically detects a variety of commonly occurring indole analogs. We demonstrate here a sensitive, specific, and rapid method for measuring indole in complex biological samples using a specific reaction between unsubstituted indole and hydroxylamine. We compared the hydroxylamine-based indole assay (HIA) to the Kovács assay and confirmed that the two assays are capable of detecting microgram amounts of indole. However, the HIA is specific to indole and does not detect other naturally occurring indole analogs. We further demonstrated the utility of the HIA in measuring indole levels in clinically relevant biological materials, such as fecal samples and bacterial cultures. Mean and median fecal indole concentrations from 53 healthy adults were 2.59 mM and 2.73 mM, respectively, but varied widely (0.30 mM to 6.64 mM) among individuals. We also determined that enterotoxigenic Escherichia coli strain H10407 produces 3.3 ؎ 0.22 mM indole during a 24-h period in the presence of 5 mM tryptophan. The sensitive and specific HIA should be of value in a variety of settings, such as the evaluation of various clinical samples and the study of indole-producing bacterial species in the gut microbiota. Indole is widely distributed in the environment and is a component of diverse important compounds that occur in nature. In the pharmaceutical industry, synthesized indoles and their modified derivatives are popularly known for their medicinal properties. Indole analogs are significant components of a number of products, including vitamin supplements, dye, over-the-counter drugs, flavor enhancers, and perfumery. They are also used in the agricultural and plastics industries. Indole has been shown to play a role in regulating bacterial biofilm formation and virulence and influences diverse physiological processes, including host immune response (1-7).Indole is produced by about 85 bacterial species, including Gram-positive and Gram-negative bacteria, through the enzymatic degradation of tryptophan (8). Once produced, indole can be chemically modified within the same bacterial cell or taken up and modified by non-indole-producing bacteria. The most common naturally occurring indole analog is 3-methylindole (skatole), although other analogs, such as indoxyl sulfate and indole-3-propionic acid, can be found (9-11).Indole production by bacteria is an important phenotypic characteristic that has long been used to differentiate, identify, and diagnose enteric bacterial infections (12). Currently, the Kovács assay (13-17) is the most widely used method for detecting indole-producing bacteria. However, the key component, para-dimethylaminobe...

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“…The continuous exposure of the gut to higher levels of metabolic products, such as biliary acids, undigested fat, and other end products of the colonic microflora (e.g. 3-methylindole), in cholecystectomised patients (Zuccato et al, 1993) might further elevate colon cancer risk. Animal models suggest that colon cancer risk increases with higher levels of secondary bile acids (Morvay et al, 1989).…”

Section: Discussionmentioning

confidence: 99%

Cholecystectomy and the risk for developing colorectal cancer and distal colorectal adenomas

et al. 2003

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Earlier work describes a modest association between cholecystectomy and the risk of colorectal cancer. We conducted a prospective study of 85 184 women, 36 -61 years old, who had no history of cancer to evaluate whether known risk factors for colorectal cancer, including dietary history, that have not been controlled for in previous analyses can help explain the observed association. During 16 years of follow-up, 877 cases of colorectal cancer were documented and 1452 women who underwent endoscopy during the follow-up time were diagnosed with distal adenomas. After adjustment for age and other known or suspected risk factors, we found a significant, positive association between cholecystectomy and the risk of colorectal cancer (multivariate relative risk RR 1.21, 95% CI 1.01 -1.46). The risk was highest for cancers of the proximal colon (RR 1.34, 95% CI 0.97 -1.88) and the rectum (RR 1.58, 95% CI 1.05 -2.36). However, we did not observe a significant association between cholecystectomy and distal colorectal adenomas. In this large prospective cohort study, a history of cholecystectomy appears to increase modestly the risk of colorectal cancer, even after adjustment for other colorectal cancer risk factors. More than 60 epidemiologic studies have investigated a possible relation between cholecystectomy and colon cancer risk. However, the strength of any association remains uncertain because of the small size and retrospective design with a failure to control for potential confounders of most analyses. A meta-analysis of studies conducted through 1993 (Giovannucci et al, 1993) observed a modest increase in the risk of colorectal cancer following cholecystectomy, although the effect was restricted primarily to the proximal colon. Two subsequent meta-analyses (Bollschweiler et al, 1993;Reid et al, 1996) and three large prospective cohort studies (Ekbom et al, 1993;Goldbohm et al, 1993;Lagergren et al, 2001) also observed an increased risk of proximal cancers, particularly among women.Most studies that examined the relation between gallstones or cholecystectomy and colorectal cancer did not adjust for other risk factors for colorectal cancer, including diet. Therefore, among those studies demonstrating a positive association, one cannot exclude potential confounding by dietary or other lifestyle factors that are jointly associated with gallstones and colorectal cancer.For the relation between cholecystectomy and colorectal cancer to be adequately characterised, large cohort studies with a long duration of follow-up and adequate assessment of potential confounding factors are necessary. We therefore utilised data from a prospective cohort study among women to illuminate further the influence of gallstones and cholecystectomy on the risk for colorectal cancer and distal colorectal adenoma. METHODS Study cohortThe Nurses' Health Study was initiated in 1976, when 121 700 female registered nurses of age 30 -55 and residing in the United States completed a mailed questionnaire on known or suspected risk factors for cancer ...

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Role of bile acids and metabolic activity of colonic bacteria in increased risk of colon cancer after cholecystectomy

Cited by 89 publications

References 46 publications

Fecal Indole as a Biomarker of Susceptibility to Cryptosporidium Infection

Fecal Indole as a Biomarker of Susceptibility to Cryptosporidium Infection

A Rapid and Specific Method for the Detection of Indole in Complex Biological Samples

Cholecystectomy and the risk for developing colorectal cancer and distal colorectal adenomas

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