Effects of Coffee on the Gastro-Intestinal Tract: A Narrative Review and Literature Update.

The objective of the present research was to review the state of the art on the consequences of drinking coffee at the different levels of the gastrointestinal tract. At some steps of the digestive process, the effects of coffee consumption seem rather clear. This is the case for the stimulation of gastric acid secretion, the stimulation of biliary and pancreatic secretion, the reduction of gallstone risk, the stimulation of colic motility, and changes in the composition of gut microbiota. Other aspects are still controversial, such as the possibility for coffee to affect gastro-esophageal reflux, peptic ulcers, and intestinal inflammatory diseases. This review also includes a brief summary on the lack of association between coffee consumption and cancer of the different digestive organs, and points to the powerful protective effect of coffee against the risk of hepatocellular carcinoma. This review reports the available evidence on different topics and identifies the areas that would most benefit from additional studies.

La vesícula biliar como reservorio y protectora del tracto digestivo / The gallbladder as reservoir and protector of the digestive tract

Introducción: Estudios anatomofisiológicos y biomoleculares de la vesícula biliar han permitido redefinir su función no solo como reservorio de la secreción biliar, sino como protectora intestinal, concepto que se fundamenta en su capacidad de control de la bioactividad y la toxicología de los ácidos biliares, el metabolismo del colesterol, los fosfolípidos y otros componentes de la secreción hepatobiliar. Objetivo: Describir las actualidades de la funcionabilidad de la vesícula biliar como reservorio y protectora del tracto digestivo dirigido a que cirujanos generales, gastroenterólogos, clínicos y fisiólogos amplíen sus conocimientos sobre la función de la vesícula biliar. Métodos: Se realiza una revisión crítica de las funciones de la vesícula biliar que favorecen mantener la integridad de la pared intestinal. Conclusión: La descripción actualizada de la funcionabilidad de la vesícula biliar ofrece un resultado relevante dentro del marco conceptual en relación a su función protectora que se traduce en el mantenimiento de la integridad del epitelio y la microbiota intestinal(AU)

Introduction: Anatomic-physiological and biomolecular studies of the gallbladder have made it possible to redefine its function not only as a reservoir for bile secretion, but also as intestinal protector. This concept is supported by its capacity to control the bioactivity and toxicology of bile acids, cholesterol metabolism, phospholipids and other components of hepatobiliary secretion. Objective: Present an update on the role of the gallbladder as reservoir and protector of the digestive tract intended for general surgeons, gastroenterologists, clinicians and physiologists to broaden their knowledge about the functions of the gallbladder. Methods: A critical review was conducted of the functions of the gallbladder which facilitate maintenance of the integrity of the intestinal wall. Conclusion: The updated description of the functions of the gallbladder is a relevant contribution to the conceptual framework of its protective function, which ensures the maintenance of the integrity of the epithelium and the intestinal microbiota(AU)

Hepatic Bile Formation: Canalicular Osmolarity and Paracellular and Transcellular Water Flow.

The purpose of this minireview is to show that a new paradigm is developing regarding hepatic bile flow. The focus thus far has been on carrier-mediated transport of bile acids and other solutes, such as glutathione, which create an osmotic gradient for the transcellular and paracellular flow of water into canaliculi. In addition to the physicochemical properties of bile acids, which govern the osmotic gradient, data now exist showing that the tight junctions governing paracellular water flow and Aquaporin-8 water channels governing transcellular water flow are regulated independently. Thus, the rate of water flow into the canaliculus in response to bile acid transport is variable and determines canalicular bile acid concentration, which affects the production and solubilization of cholesterol-lecithin vesicles. These new considerations modify thinking regarding the occurrence of cholestasis and its progression and reorient the design of experimental studies that can distinguish the different determinants of bile flow. SIGNIFICANCE STATEMENT: The paradigm that water flow into the canaliculus is determined only by the rate of carrier-mediated transport has been challenged recently by the changes that occur in hepatic bile composition in the Claudin-2 knockout mouse and with the cholestatic effect of estradiol 17ß-d-glucuronide. Thus, a respective reduction in paracellular or transcellular canalicular water flow, probably via Aquaporin 8, has no significant effect on bile acid excretion.

Identification of a novel function of hepatic long-chain acyl-CoA synthetase-1 (ACSL1) in bile acid synthesis and its regulation by bile acid-activated farnesoid X receptor.

Long-chain acyl-CoA synthetase 1 (ACSL1) plays a pivotal role in fatty acid ß­oxidation in heart, adipose tissue and skeletal muscle. However, key functions of ACSL1 in the liver remain largely unknown. We investigated acute effects of hepatic ACSL1 deficiency on lipid metabolism in adult mice under hyperlipidemic and normolipidemic conditions. We knocked down hepatic ACSL1 expression using adenovirus expressing a ACSL1 shRNA (Ad-shAcsl1) in mice fed a high-fat diet or a normal chow diet. Hepatic ACSL1 depletion generated a hypercholesterolemic phenotype in mice fed both diets with marked elevations of total cholesterol, LDL-cholesterol and free cholesterol in circulation and accumulations of cholesterol in the liver. Furthermore, SREBP2 pathway in ACSL1 depleted livers was severely repressed with a 50% reduction of LDL receptor protein levels. In contrast to the dysregulated cholesterol metabolism, serum triglycerides, free fatty acid and phospholipid levels were unaffected. Mechanistic investigations of genome-wide gene expression profiling and pathway analysis revealed that ACSL1 depletion repressed expressions of several key enzymes for bile acid biosynthesis, consequently leading to reduced liver bile acid levels and altered bile acid compositions. These results are the first demonstration of a requisite role of ACSL1 in bile acid biosynthetic pathway in liver tissue. Furthermore, we discovered that Acsl1 is a novel molecular target of the bile acid-activated farnesoid X receptor (FXR). Activation of FXR by agonist obeticholic acid repressed the expression of ACSL1 protein and mRNA in the liver of FXR wild-type mice but not in FXR knockout mice.

Proper bile duct flow, rather than radical excision, is the most critical factor determining treatment outcomes of bile duct cysts.

BACKGROUND: The purpose of this study was to compare the impact of the extent of excision and the patent bile duct flow on treatment outcomes of bile duct cysts (BDCs). METHODS: We retrospectively analyzed the records of 382 patients who received surgery for BDCs from January 2005 to December 2014. RESULTS: For Type Ia cysts, proper bile flow was associated with good long-term treatment outcomes with a greater level of significance (p < 0.001) than complete excision (p = 0.012). For Type IVa cysts, proper bile flow, but not complete excision, was associated with good long-term outcomes (p < 0.00001). In addition, 96.3% (104/108) of Type IVa patients with proper bile flow had no late complications and good biliary function, while no patient without patent bile flow had a good clinical outcome. For Type Ic cysts, 92 patients who received partial excisions had good outcomes when proper bile flow was restored. Regression analysis revealed that the absence of proper bile flow, in comparison to incomplete excision, is a greater risk factor for poor long-term treatment effects for Type Ia and Type IVa cysts. CONCLUSIONS: Compared to complete excision, the establishment of proper bile flow exerted a greater impact on improving long-term clinical outcomes after BDC surgery.

Biliary tract external drainage improves inflammatory mediators and pathomorphology of the intestine, liver, and lung in septic rats.

BACKGROUND: To investigate the effect of biliary tract external drainage (BTED) on inflammatory mediators and pathomorphism of intestine, liver, and lung in septic rats. METHOD: 48 SD rats (n = 8 per group) were randomized into six groups: control, sepsis, sepsis plus BTED, normal bile (obtained from eight healthy rats), and septic bile infusion for 6 hours respectively to test the effects of BTED bile infusion on cytokines' expression and tissue injury in the intestine, liver, and lung of septic/normal rats. Co-cultivation of intestinal epithelial cells (IEC-6) with bile for 12 hours was performed to evaluate the potential cytotoxicity of septic bile. Survival rate for sepsis plus BTED rats was detected compared with sepsis without BTED group (n = 20 per group) at 24, 48, and 72 hours, respectively. RESULTS: BTED for 6 hours significantly reduced the mRNA expression levels of tumor necrosis factor alpha (TNF-α) and IL-1ß (all p < 0.05 vs. sepsis group), whereas mRNA expression of TNF-α and IL-1ß in the intestine was increased after 6 hours' septic bile infusion compared with normal bile infusion group (all p < 0.05). TNF-α concentration in septic bile was significantly higher than that in the control group (p < 0.001). Tissue injury was significantly attenuated after 6 hours' BTED. CONCLUSIONS: BTED can significantly restrain the mRNA expression of TNF-α and IL-1ß in the intestine, liver, and lung and attenuate histological damage in septic rats.

Bile Gastritis Following Laparoscopic Single Anastomosis Gastric Bypass: Pilot Study to Assess Significance of Bilirubin Level in Gastric Aspirate.

INTRODUCTION: Laparoscopic single anastomosis gastric bypass (SAGB) is increasingly performed for morbidly obese patients. AIM OF WORK: This pilot study aims primarily at evaluating the incidence of bile gastritis after SAGB. The occurrence of reflux oesophagitis and reflux symptoms were also assessed. PATIENTS AND METHODS: This study included 20 patients having no reflux symptoms. All patients underwent a SAGB as a primary bariatric procedure by a single surgeon. Patients included consented to have an upper GI endoscopy done at 6 months postoperatively. Gastric aspirate was sent for bilirubin level assessment. Gastric and esophageal biopsies were submitted for histopathology and campylobacter-like organism (CLO) test. RESULTS: In our study, the rate of bile gastritis was 30%. In 18 patients, the level of bilirubin in gastric aspirate seems to be related to the degree of mucosal inflammation. The remaining two patients had microscopic moderate to severe gastritis with normal aspirate bilirubin level. Two patients with bilirubin level in aspirate more than 20 mg/dl had severe oesophagitis, gastritis with erosions, and metaplasia. Relationship between bilirubin level and histopathological findings of gastric biopsy examination was statistically significant with a P value of 0.001. CONCLUSION: The incidence of bile gastritis in this cohort is higher than reported in the literature, and this may be worrying. The correlation between endoscopic findings and patients' symptoms is poor. Bilirubin level and pH in aspirate might be useful tools to confirm alkaline reflux. Its level might help to choose candidates for revision surgery after SAGB. This needs further validation with larger sample size.

The Role of Acid Suppression in Barrett's Esophagus.

In recent years, proton pump inhibitors (PPIs) have come under great scrutiny due to possible adverse, long-term side effects. At the same time, Barrett's esophagus, a premalignant condition in the esophagus, continues to be a disease whose course is thought to be improved by the use of PPIs. We review the impact of proton pump therapy on the esophagus and on Barrett's mucosa. In analyzing changes on a cellular level, we explore the effect of mixed gastric refluxate and the complex cascade that ensues with esophageal exposure of these contents. Because the incidence of esophageal adenocarcinoma is on the rise, we explore other factors that may contribute to the progression of Barrett's from non-dysplastic mucosa to esophageal adenocarcinoma. By revisiting the need for adequate acid suppression in Barrett's and increasing our understanding of other possible factors that may have an effect of Barrett's progression, we hope to support our multifaceted approach to acid suppression in patients with Barrett's esophagus.

Resistant starch can improve insulin sensitivity independently of the gut microbiota.

BACKGROUND: Obesity-related diseases, including type 2 diabetes and cardiovascular disease, have reached epidemic proportions in industrialized nations, and dietary interventions for their prevention are therefore important. Resistant starches (RS) improve insulin sensitivity in clinical trials, but the mechanisms underlying this health benefit remain poorly understood. Because RS fermentation by the gut microbiota results in the formation of physiologically active metabolites, we chose to specifically determine the role of the gut microbiota in mediating the metabolic benefits of RS. To achieve this goal, we determined the effects of RS when added to a Western diet on host metabolism in mice with and without a microbiota. RESULTS: RS feeding of conventionalized mice improved insulin sensitivity and redressed some of the Western diet-induced changes in microbiome composition. However, parallel experiments in germ-free littermates revealed that RS-mediated improvements in insulin levels also occurred in the absence of a microbiota. RS reduced gene expression of adipose tissue macrophage markers and altered cecal concentrations of several bile acids in both germ-free and conventionalized mice; these effects were strongly correlated with the metabolic benefits, providing a potential microbiota-independent mechanism to explain the physiological effects of RS. CONCLUSIONS: This study demonstrated that some metabolic benefits exerted by dietary RS, especially improvements in insulin levels, occur independently of the microbiota and could involve alterations in the bile acid cycle and adipose tissue immune modulation. This work also sets a precedent for future mechanistic studies aimed at establishing the causative role of the gut microbiota in mediating the benefits of bioactive compounds and functional foods.

Bile Routing Modification Reproduces Key Features of Gastric Bypass in Rat.

OBJECTIVE: To evaluate the role of bile routing modification on the beneficial effects of gastric bypass surgery on glucose and energy metabolism. BACKGROUND: Gastric bypass surgery (GBP) promotes early improvements in glucose and energy homeostasis in obese diabetic patients. A suggested mechanism associates a decrease in hepatic glucose production to an enhanced intestinal gluconeogenesis. Moreover, plasma bile acids are elevated after GBP and bile acids are inhibitors of gluconeogenesis. METHODS: In male Sprague-Dawley rats, we performed bile diversions from the bile duct to the midjejunum or the mid-ileum to match the modified bile delivery in the gut occurring in GBP. Body weight, food intake, glucose tolerance, insulin sensitivity, and food preference were analyzed. The expression of gluconeogenesis genes was evaluated in both the liver and the intestine. RESULTS: Bile diversions mimicking GBP promote an increase in plasma bile acids and a marked improvement in glucose control. Bile bioavailability modification is causal because a bile acid sequestrant suppresses the beneficial effects of bile diversions on glucose control. In agreement with the inhibitory role of bile acids on gluconeogenesis, bile diversions promote a blunting in hepatic glucose production, whereas intestinal gluconeogenesis is increased in the gut segments devoid of bile. In rats fed a high-fat-high-sucrose diet, bile diversions improve glucose control and dramatically decrease food intake because of an acquired disinterest in fatty food. CONCLUSIONS: This study shows that bile routing modification is a key mechanistic feature in the beneficial outcomes of GBP.

Altered intestinal bile salt biotransformation in a cystic fibrosis (Cftr-/-) mouse model with hepato-biliary pathology.

BACKGROUND: Cftr(-/-tm1Unc) mice develop progressive hepato-biliary pathology. We hypothesize that this liver pathology is related to alterations in biliary bile hydrophobicity and bile salt metabolism in Cftr(-/-tm1Unc) mice. METHODS: We determined bile production, biliary and fecal bile salt- and lipid compositions and fecal bacterial composition of C57BL/6J Cftr(-/-tm1Unc) and control mice. RESULTS: We found no differences between the total biliary bile salt or lipid concentrations of Cftr(-/-) and controls. Compared to controls, Cftr(-/-) mice had a ~30% higher bile production and a low bile hydrophobicity, related to a ~7 fold higher concentration of the choleretic and hydrophilic bile salt ursocholate. These findings coexisted with a significantly smaller quantity of fecal Bacteroides bacteria. CONCLUSIONS: Liver pathology in Cftr(-/-tm1Unc) is not related to increased bile hydrophobicity. Cftr(-/-) mice do however display a biliary phenotype characterized by increased bile production and decreased biliary hydrophobicity. Our findings suggest Cftr dependent, alterations in intestinal bacterial biotransformation of bile salts.

Hepatobiliary physiological changes after Roux-en-Y cholecysto-colonic diversion.

BACKGROUND: We speculated that Roux-en-Y cholecysto-colonic diversion was as effective for treating children with progressive familial intrahepatic cholestasis (PFIC) as partial biliary diversion. The feasibility of the novel approach in bypassing bile was investigated in rabbits. METHODS: Twenty-four rabbits were randomly divided into three groups: sham operated group (Group1), 30cm limb group (Group 2), and 10 cm limb group (Group 3). Group 2 or 3 underwent a Roux-en-Y cholecystocolonic anastomoses with a 30- or 10-cm-long Roux limb. (99mTc)EHIDA dynamic biligraphy was used to detect alterations of bile flow among the three groups at 1 year postoperatively. TBA levels and histological changes were also evaluated. RESULTS: All animals survived and developed normally without clinical symptoms during 1 year follow-up. Bile was diverted into colon directly after cholecystocolonic anastomosis. In group 3, E20 and E35 values were (77.27 ± 6.15%) and (90.39 ± 1.49%) respectively. Gallbladder emptying was accelerated in 10 cm short limb group than in 30 cm long limb group. The ratio of bile shunt was (0.547 ± 0.182), which was also more than that in group 2 (p<0.05). The activity-time curve for the gallbladder area in group 2 looks like a wave. A significant reduction in TBA level was observed in group 2 and 3 (p<0.05). CONCLUSIONS: Roux-en-Y cholecystocolonic bypass was safe and feasible. Its effectiveness is related to the length of Roux loop. Cholecystocolonic bypass led to a significant loss of bile acids in healthy rabbits and might be considered for bile diversion in pediatric patients with selected cholestatic diseases.

Physiology of cholangiocytes.

Cholangiocytes are epithelial cells that line the intra- and extrahepatic ducts of the biliary tree. The main physiologic function of cholangiocytes is modification of hepatocyte-derived bile, an intricate process regulated by hormones, peptides, nucleotides, neurotransmitters, and other molecules through intracellular signaling pathways and cascades. The mechanisms and regulation of bile modification are reviewed herein.

Effect of heat treatment on viability of Taenia hydatigena eggs.

Effects of heat treatments on activation and infectivity of Taenia hydatigena eggs were assessed. Eggs containing oncospheres were used for in vitro and in vivo studies to determine the response to 5min of heat treatment, ranging from room temperature (22°C) to 60°C. The study demonstrated 99.47% and 100% reduction in oncosphere activation or infectivity after 5min of heat treatment at 60°C and 57.38°C under in vitro and in vivo conditions, respectively. Similar results between the two approaches indicted the appropriateness of the in vitro methods to identify oncosphericidal treatments of practical significance. Similar heat treatments may also be effective against Taenia saginata and help to reduce occurrence of beef cysticercosis.

Evidence that estrogen receptors play a limited role in mediating enhanced recovery of bile flow in female rats in the acute phase of liver ischemia reperfusion injury.

INTRODUCTION: Female patients exhibit better survival and less hepatic damage from ischemia reperfusion (IR) injury following surgery. However, the effects of sex and estrogens on liver function in the acute phase of IR are not well understood. Objective. The aim was to investigate this question. MATERIAL AND METHODS: A rat model of segmental hepatic ischemia was employed. Rats were pre-treated with the estrogen receptor antagonist ICI182,780 and/or the estrogen receptor agonist 17ß-estradiol. Bile flow, blood concentrations of bilirubin and liver enzymes were measured, and liver histology was assessed. RESULTS: Bile flow recovery immediately after the initiation of reperfusion was faster in females than in males. ICI182,780 reduced the rate of bile flow recovery in females but this reduction was not reversed by co-administration of 17 ß-estradiol. In males, 17 ß-estradiol alone did not enhance bile flow recovery. The changes in bile flow recovery observed under a given condition were correlated with small changes in blood liver enzymes and liver histology. CONCLUSIONS: Sex has a significant influence on the early recovery of liver function in the acute phase of IR injury. However, in female rats estrogen receptors play only a limited role in mediating enhanced recovery of liver function.

Fibrinolytic proteins in human bile accelerate lysis of plasma clots and induce breakdown of fibrin sealants.

OBJECTIVE: We investigated the effect of human bile on the stability of plasma clots and of fibrin sealants. BACKGROUND: Fibrin sealants are extensively used in liver surgery, for example, during liver resections. Although these sealants have been developed to induce hemostasis, in practice these products are actually mainly used to seal dissected bile ducts to prevent postsurgical bile leakage. METHODS: We performed in vitro assays in which clotting and lysis of human plasma clots or fibrin sealants was studied in presence or absence of human bile. RESULTS: Addition of bile to human plasma resulted in a dose-dependent increase in clotting time, and a dose-dependent decrease in clot lysis time. Bile also accelerated lysis of in vitro clotted fibrin sealants. Immunodepletion of tissue-type plasminogen activator (tPA) resulted in partial depletion of the lysis promoting activity of bile. Immunodepletion of both tPA and lysine-binding proteins from bile fully abolished the lytic activity, suggesting that tPA and plasminogen present in human bile are responsible for the lysis-promoting effect. Surprisingly, addition of high dose plasminogen activator inhibitor type 1 (PAI-1) to bile did not attenuate the lytic activity toward fibrin sealants, which suggested that tPA in a biliary environment may be unsusceptible to PAI-1 inhibition. Indeed, bile acids were shown to prevent tPA from interacting with PAI-1, although preformed complexes were not destabilized upon addition of bile acids. CONCLUSIONS: These combined results suggest that the presence of tPA and other fibrinolytic proteins in human bile results in lysis of plasma clots or fibrin sealants, which potentially could affect the efficacy of the latter products.

The role of bile after Roux-en-Y gastric bypass in promoting weight loss and improving glycaemic control.

Gastric bypass leads to the remission of type 2 diabetes independently of weight loss. Our hypothesis is that changes in bile flow due to the altered anatomy may partly explain the metabolic outcomes of the operation. We prospectively studied 12 patients undergoing gastric bypass and six patients undergoing gastric banding over a 6-wk period. Plasma fibroblast growth factor (FGF)19, stimulated by bile acid absorption in the terminal ileum, and plasma bile acids were measured. In canine and rodent models, we investigated changes in the gut hormone response after altered bile flow. FGF19 and total plasma bile acids levels increased after gastric bypass compared with no change after gastric banding. In the canine model, both food and bile, on their own, stimulated satiety gut hormone responses. However, when combined, the response was doubled. In rats, drainage of endogenous bile into the terminal ileum was associated with an enhanced satiety gut hormone response, reduced food intake, and lower body weight. In conclusion, after gastric bypass, bile flow is altered, leading to increased plasma bile acids, FGF19, incretin. and satiety gut hormone concentrations. Elucidating the mechanism of action of gastric bypass surgery may lead to novel treatments for type 2 diabetes.

Bile exposure inhibits expression of squamous differentiation genes in human esophageal epithelial cells.

OBJECTIVE: This study aimed to identify pathways and cellular processes that are modulated by exposure of normal esophageal cells to bile and acid. BACKGROUND: Barrett's esophagus most likely develops as a response of esophageal stem cells to the abnormal reflux environment. Although insights into the underlying molecular mechanisms are slowly emerging, much of the metaplastic process remains unknown. METHODS: We performed a global analysis of gene expression in normal squamous esophageal cells in response to bile or acid exposure. Differentially expressed genes were classified into major biological functions using pathway analysis and interaction network software. Array data were verified by quantitative PCR and western blot both in vitro and in human esophageal biopsies. RESULTS: Bile modulated expression of 202 genes, and acid modulated expression of 103 genes. Genes involved in squamous differentiation formed the largest functional group (n = 45) all of which were downregulated by bile exposure. This included genes such as involucrin (IVL), keratinocyte differentiation-associated protein (KRTDAP), grainyhead-like 1 (GRHL1), and desmoglein1 (DSG1) the downregulation of which was confirmed by quantitative PCR and western blot. Bile also caused expression changes in genes involved in cell adhesion, DNA repair, oxidative stress, cell cycle, Wnt signaling, and lipid metabolism. Analysis of human esophageal biopsies demonstrated greatly reduced expression of IVL, KRTDAP, DSG1, and GRHL1 in metaplastic compared to squamous epithelia. CONCLUSIONS: We report for the first time that bile inhibits the squamous differentiation program of esophageal epithelial cells. This, coordinated with induction of genes driving intestinal differentiation, may be required for the development of Barrett's esophagus.

The intestinal microbiota, gastrointestinal environment and colorectal cancer: a putative role for probiotics in prevention of colorectal cancer?

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the United States, and, even though 5-15% of the total CRC cases can be attributed to individual genetic predisposition, environmental factors could be considered major factors in susceptibility to CRC. Lifestyle factors increasing the risks of CRC include elevated body mass index, obesity, and reduced physical activity. Additionally, a number of dietary elements have been associated with higher or lower incidence of CRC. In this context, it has been suggested that diets high in fruit and low in meat might have a protective effect, reducing the incidence of colorectal adenomas by modulating the composition of the normal nonpathogenic commensal microbiota. In addition, it has been demonstrated that changes in abundance of taxonomic groups have a profound impact on the gastrointestinal physiology, and an increasing number of studies are proposing that the microbiota mediates the generation of dietary factors triggering colon cancer. High-throughput sequencing and molecular taxonomic technologies are rapidly filling the knowledge gaps left by conventional microbiology techniques to obtain a comprehensive catalog of the human intestinal microbiota and their associated metabolic repertoire. The information provided by these studies will be essential to identify agents capable of modulating the massive amount of gut bacteria in safe noninvasive manners to prevent CRC. Probiotics, defined as "live microorganisms which, when administered in adequate amounts, confer a health benefit on the host" (219), are capable of transient modulation of the microbiota, and their beneficial effects include reinforcement of the natural defense mechanisms and protection against gastrointestinal disorders. Probiotics have been successfully used to manage infant diarrhea, food allergies, and inflammatory bowel disease; hence, the purpose of this review was to examine probiotic metabolic activities that may have an effect on the prevention of CRC by scavenging toxic compounds or preventing their generation in situ. Additionally, a brief consideration is given to safety evaluation and production methods in the context of probiotics efficacy.