Biomedical subjects

I R Rowland

Publications and source records attributed to I R Rowland.

At least 19 recordsLinked to original sources

PubMed2003

A human flora-associated rat model of the breast-fed infant gut.

OBJECTIVES: Bacterial colonization of the infant gut may have important influences on the development of gastrointestinal, respiratory, and allergic disease. Early diet is a major determinant of the gut microflora. It is very difficult to carry out studies in human infants that can investigate the interaction of diet, flora, and mucosa. In this study we have developed an infant human flora-associated (IHFA) rat model to allow such investigation. METHODS: Germ-free infant rats were infected with fecal bacteria from exclusively breast-fed infants and were maintained on a modified infant formula for 8 weeks. The fecal and cecal contents were collected and compared with feces of breast-fed infants for bacterial populations, bacterial metabolites, and enzymes and for the ability to inhibit adhesion of pathogenic bacteria to human mucosal cells. RESULTS: The IHFA cecum and feces were dominated by lactic acid bacteria, Bifidobacterium, and lactobacilli, which were representative of the infant feces. The fecal short-chain fatty acid profile was dominated by acetic and lactic acid in a similar manner to human infant feces. Other bacterial metabolites were similar to those of the human infant. Rat intestinal samples were able to inhibit the adhesion of pathogens to mucosal cells, but to a lesser extent than the human samples. CONCLUSIONS: This IHFA infant model of the intestinal flora of the breast-fed infant is considered valid for studying the effect of diet on bacterial colonization and metabolism.

Animals↗

PubMed2002

Influence of dietary components associated with high or low risk of colon cancer on apoptosis in the rat colon.

Although there is much epidemiological evidence for an interaction between diet and colorectal cancer risk, the mechanisms by which diet might protect against colorectal cancer are still unclear. Here we report the significant up-regulation of carcinogen-induced apoptosis in the colon of rats fed a diet containing low-risk factors for colon cancer, namely low fat content, high calcium and high non-digestible carbohydrate. The dose-dependent induction of apoptosis in colonic crypts by the carcinogen 1,2-dimethylhydrazine (DMH) was significantly greater in rats receiving the low-risk compared with a high-risk (high fat, low calcium, low non-digestible carbohydrate) diet (P<0.001). There were also significant interactions of colon region with DMH dose and region by diet, with the greatest increases in apoptosis occurring in the mid and distal regions of the colon compared with the proximal region. Since we have previously shown the low-risk diet to be non-toxic, these new results suggest a diet-induced up-regulation of apoptosis, which may represent a mechanism of protection against the early stages of carcinogenesis in the colon.

Animals↗

PubMed2002

Dose-response effects of a novel fat emulsion (Olibra) on energy and macronutrient intakes up to 36 h post-consumption.

OBJECTIVE: To investigate the dose-response effects of a novel fat emulsion (Olibra) on energy and macronutrient intakes up to 36 h post-consumption in non-overweight subjects. DESIGN: A single-blind, placebo-controlled, within-subject cross-over design was used. SETTING: Metabolic suite of the University of Ulster, Coleraine. SUBJECTS: Fifty subjects (30 female, 20 male) from the student and staff population of the University of Ulster, Coleraine. INTERVENTIONS: Subjects were given in random order, 7 days apart, a 200 g portion of yoghurt containing a total of 15 g of fat, which varied in quantity of Olibra fat (0, 2, 4, 6 g) at 09:00 h. At 13:00 h subjects were given ad libitum access to a range of foods. Amounts of food consumed were measured by covert pre- and post-consumption weighing of individual serving dishes. For the remainder of the day and the following 24 h, subjects weighed and recorded all food intakes. RESULTS: Relative to the control yoghurt, mean energy (7.42 vs 5.83, 5.60, 5.24 MJ), fat (97.4 vs 74.4, 74.2, 67.5 g; 48.8 vs 46.8, 48.9, 47.6% energy), protein (59.1 vs 50.0, 44.0, 40.8 g; 13.2 vs 13.9, 12.9, 12.8% energy), and carbohydrate (171.5 vs 140.9, 130.2, 126.0 g; 38.0 vs 39.3, 38.2, 39.6% energy), intakes were progressively reduced with increasing doses of Olibra fat in the total group (P<0.001). A similar response was observed in the female group up to 4 g (P<0.001) and in the male group after 2 and 6 g (P<0.05). Energy and macronutrient intakes for the remainder of each study day and over the following 24 h were significantly lower after all dose levels compared to the control (P<0.001). CONCLUSION: The results suggest that Olibra fat reduced the effect of overeating during an ad libitum lunch meal and subsequent food intake up to 36 h post-consumption.

Adult↗

PubMed2002

Monitoring transfer of recombinant and nonrecombinant plasmids between Lactococcus lactis strains and members of the human gastrointestinal microbiota in vivo--impact of donor cell number and diet.

AIMS: The generation of data of real relevance to the purported risks of DNA transfer from food-borne genetically modified microorganisms (GMMOs) using the human biota associated (HBA) rat model. Plasmid transfer between Lactococcus lactis strains and between donor strains and human gut bacteria was monitored. METHODS AND RESULTS: Transfer of the recombinant plasmid pCK1 and/or the promiscuous nonrecombinant plasmid pAMbeta1 between L. lactis strains was monitored in vivo in HBA rats. No transfer of pCK1 was observed. Transfer of pAMbeta1 was observed to Enterococcus spp. present in the HBA rats. Transconjugants persisted for 30 d and were distributed throughout the gastrointestinal tract. Both HBA rat diet and donor cell numbers impacted on transconjugant numbers. Fewer transconjugants were observed in animals fed a high-fat human type diet, while high levels of plasmid transfer were only observed at doses of donor L. lactis greater than 109 cfu. CONCLUSIONS: The utility of models of the human gut in monitoring DNA transfer events within the gut microbiota was demonstrated. SIGNIFICANCE AND IMPACT OF THE STUDY: Such findings give some confidence for the use of GMMOs with recombinant DNA borne on nonconjugative elements in fermented foods. HBA rats are a suitable model for monitoring the fate of food-borne GMMOs.

Animals↗

PubMed2002

Diet and cancer: assessing the risk.

Globally, colorectal cancer (CRC) is a leading cause of mortality from malignant disease. Case-control and cohort studies provide strong support for a role of diet in the aetiology of CRC. However to establish causal relationships and to identify more precisely the dietary components involved, intervention studies in human subjects are required. Cancer is an impractical endpoint in terms of numbers, cost, study duration and ethical considerations. Consequently, intermediate biomarkers of the disease are required. This review aims to provide an overview of the intermediate endpoints available for the study of CRC, particularly non-invasive faecal biomarkers. Examples of their use in dietary intervention studies are given.

Biomarkers, Tumor↗

PubMed2002

Genetically modified foods, science, consumers and the media.

In contrast to the situation in the USA, where a wide range of genetically modified (GM) foods is available, in Europe very few GM products have been approved for marketing as foods, and there is widespread public concern about their safety and environmental impact. The marketing of a GM crop for food use in Europe falls under the EC novel foods regulations, and applications require the submission of an extensive dossier of information. The safety evaluation of GM foods presents considerable problems both in the conduct and interpretation of experimental studies, because conventional toxicity tests used in the evaluation of simple chemicals may not be appropriate for whole foods. To rationalise the safety evaluation process and to circumvent the difficulties in toxicological assessment of food materials, the concept of substantial equivalence has been developed. The concept is that if it can be demonstrated that the novel food is essentially similar to its conventional counterpart in terms of critical nutritional or anutritional components, then it is likely to be no more or less toxic than the latter. The possible introduction of unintended effects by the genetic modification process is particularly problematic for the safety evaluation process. The new genomic and post-genomic techniques are potentially valuable in the safety evaluation of GM foods, although they are as yet in their infancy.

Animals↗

PubMed2001

Effect of lactobacilli, bifidobacteria and inulin on the formation of aberrant crypt foci in rats.

BACKGROUND: Our studies were aimed at investigating the effect of lactic acid producing bacteria (LAB) or inulin, a natural source of non-digestible oligosaccharides derived from chicory, on the induction by carcinogens of aberrant crypt foci (ACF) in the colon, which are considered to be early precursor lesions of neoplasia. METHODS: Strains of Bifidobacterium longum, Lactobacillus casei and Lactobacillus acidophilus were administered to rats fed a purified high starch diet, under a variety of treatment protocols including daily gavage, via the drinking water and in the diet. The rats were treated with methyl-N-nitrosourea, 1,2-dimethylhydrazine, or azoxymethane (AOM) to induce ACF. RESULTS: In general, no consistent significant changes in ACF numbers were detected in these experiments. In one study, the basal diet of the rats was changed to one containing a higher level of fat (corn oil). Under these conditions, a significant decrease in AOM-induced colonic ACF was seen in rats given L. acidophilus or inulin. In a concurrent group of animals fed a low fat diet, no significant decrease in ACF was observed. CONCLUSIONS: The results indicate that the type of diet fed can influence the detection of protective effects of LAB and oligosaccharides and that against the background of a diet with a level of fat typical of a Western diet, evidence for a protective effect of L. acidophilus and inulin towards colon cancer was obtained

1,2-Dimethylhydrazine↗

PubMed2001

The effects of yoghurt containing a novel fat emulsion on energy and macronutrient intakes in non-overweight, overweight and obese subjects.

OBJECTIVE: To investigate the effects of a yoghurt containing a novel fat emulsion on energy and macronutrient intakes up to 8 h post-consumption in non-overweight, overweight and obese subjects, and to assess energy compensation over the following 24 h. DESIGN: A double-blind, placebo-controlled, within-subject crossover design was used. Twenty (10 female, 10 male) non-overweight (body mass index (BMI) 20-24.9 kg/m(2)), 20 (10 female, 10 male) overweight (BMI 25-29.9 kg/m(2)) and 20 (13 female, 7 male) obese (BMI>30 kg/m(2)) subjects participated in the study. Subjects were given in random order, 7 days apart, either a 200 g portion of a test (5 g of a novel fat emulsion+1 g milk fat) or control (6 g milk fat) yoghurt at 09:00 h. At 4 and 8 h post-consumption subjects were given ad libitum access to a range of foods. Amounts of food consumed were determined by pre and post-covert weighing of individual serving dishes. Over the following 24 h subjects weighed and recorded all food intakes. RESULTS: Mean energy intakes were significantly lower after the test yoghurt compared with the control yoghurt in non-overweight (3.79 vs 5.43 MJ; P<0.01) and overweight (4.43 vs 6.12 MJ; P<0.001) subjects 4 h post-consumption and in non-overweight (3.82 vs 5.38 MJ; P<0.001), overweight (3.94 vs 5.80 MJ; P<0.001) and obese (4.91 vs 6.26 MJ; P<0.01) subjects 8 h post-consumption. The corresponding macronutrient intakes were also significantly reduced in non-overweight and overweight subjects (P<0.01) at 4 h post-consumption and in all subjects 8 h post-consumption (P<0.01). In the total group, energy intakes over the following 24 h were also significantly reduced (6.35 vs 7.70 MJ; P<0.01) after the test yoghurt relative to the control yoghurt. CONCLUSIONS: These results suggest that the effects of this novel fat emulsion are maintained at least up to 8 h and are evident in non-overweight, overweight and obese subjects.

Adult↗

PubMed2001

Stimulation of apoptosis by two prebiotic chicory fructans in the rat colon.

Prebiotics, in particular the chicory derived beta(2-1) fructans, have been shown to exert cancer protective effects in animal models. The present study was carried out to determine the effects of two chicory fructans--oligofructose (RaftiloseP95; average degree of polymerization DP = 4) and long chain inulin (RaftilineHP; average DP = 25), on apoptosis and bacterial metabolism associated with carcinogenesis. Eighteen rats were fed a stock diet for one week. Three groups of six animals were then fed one of three diets: basal, basal with oligofructose (5%w/w) or basal with long chain inulin (5%w/w), for a three week period. All animals were then dosed with 1,2-dimethylhydrazine and killed 24 h later. The mean number of apoptotic cells per crypt was significantly higher in the colon of rats fed oligofructose (P = 0.049) and long chain inulin (P = 0.017) as compared to those fed the basal diet alone. This suggests that oligofructose as well as the long chain inulin exert protective effects at an early stage in the onset of cancer, as the supplements were effective soon after the carcinogen insult. Comparison of the apoptotic indices between the two oligosaccharide diets showed no significant difference even though the mean apoptotic index was higher in animals fed long chain inulin. For all animals, apoptosis was significantly higher in the distal colon as compared to the proximal colon (P = 0.0002) however no significant site specific effect of diet occurred. There were no significant dietary effects on bacterial enzyme activities or ammonia concentration despite a trend towards increased colonic beta-glucosidase and reduced ammonia concentration during the oligosaccharide diets. This is the first time that a significant effect of chicory fructans on apoptosis has been shown and the results contribute to the growing evidence that chicory fructans may have cancer preventing properties.

Ammonia↗

PubMed2000

Short-term effects of yoghurt containing a novel fat emulsion on energy and macronutrient intakes in non-obese subjects.

BACKGROUND: The satiating properties of fat remain poorly understood, particularly with reference to its physicochemical characteristics. OBJECTIVE: To investigate the short-term effects of consumption of yoghurt containing either a novel fat emulsion or normal milk fat, on the energy and macronutrient intakes of non-obese subjects. DESIGN: Two double-blind, placebo-controlled, within-subject crossover studies were conducted three months apart. Twenty-nine (15 F, 14 M) and thirty (16 F, 14 M) subjects participated in Study 1 and Study 2 respectively. In each study, subjects were given in random order, 7 days apart, either a 200g portion of a test (5g of a novel fat emulsion + 1 g milk fat) or control (6g milk fat) yoghurt at 1300 h. At 4h post-consumption subjects were given ad libitum access to a range of foods. Amounts of food consumed by individuals were determined by pre- and post-covert weighing of individual serving dishes. RESULTS: Mean energy intakes were significantly lower after the test yoghurt compared with the control yoghurt in Study 1 (6.4 vs 7.6 MJ; P< 0.001), Study 2 (6.9 vs 7.9 MJ; P<0.001), and for both studies combined (6.7 vs 7.7 MJ; P<0.001). The corresponding fat intakes in Study 1, Study 2 and in the combined studies were all significantly reduced (P< 0.001). Protein and carbohydrate intakes were also significantly reduced in Study 1 (P< 0.05), Study 2 (P< 0.01), and for the combined studies (P< 0.001). CONCLUSIONS: These results suggest that the physicochemical characteristics of small amounts of dietary fat affect short-term satiety.

Adult↗

PubMed2000

Isoflavone phytoestrogens consumed in soy decrease F(2)-isoprostane concentrations and increase resistance of low-density lipoprotein to oxidation in humans.

BACKGROUND: Oxidative damage to lipids may be involved in the etiology of atherosclerosis, cardiovascular disease in general, and cancer. The soy isoflavone phytoestrogens, genistein and daidzein, and equol (a daidzein metabolite produced by intestinal microflora) are antioxidants in vitro; equol is a particularly good inhibitor of LDL oxidation and membrane lipid peroxidation. OBJECTIVE: We sought to investigate the effects of a diet enriched with soy containing isoflavones on in vivo biomarkers of lipid peroxidation and resistance of LDL to oxidation, compared with a diet enriched with soy from which the isoflavones had been extracted. DESIGN: : A randomized, crossover design was used to compare diets enriched with soy that was low or high in isoflavones in 24 subjects. Plasma concentrations of an F(2)-isoprostane, 8-epi-prostaglandin F(2)(alpha) (8-epi-PGF(2)(alpha)), a biomarker of in vivo lipid peroxidation, and resistance of LDL to copper-ion-induced oxidation were determined. RESULTS: Plasma concentrations of 8-epi-PGF(2)(alpha) were significantly lower after the high-isoflavone dietary treatment than after the low-isoflavone dietary treatment (326 +/- 32 and 405 +/- 50 ng/L, respectively; P = 0.028) and the lag time for copper-ion-induced LDL oxidation was longer (48 +/- 2.4 and 44 +/- 1.9 min, respectively; P = 0.017). Lag time for oxidation of unfractionated plasma and plasma concentrations of malondialdehyde, LDL alpha-tocopherol, polyunsaturated fatty acids, and isoflavonoids did not differ significantly between dietary treatments. CONCLUSIONS: Consumption of soy containing naturally occurring amounts of isoflavone phytoestrogens reduced lipid peroxidation in vivo and increased the resistance of LDL to oxidation. This antioxidant action may be significant with regard to risk of atherosclerosis, cardiovascular disease in general, and cancer.

Adult↗

PubMed2000

Interindividual variation in metabolism of soy isoflavones and lignans: influence of habitual diet on equol production by the gut microflora.

The soy isoflavones, daidzein and genistein, and the lignans, matairesinol and secoisolariciresinol, are phytoestrogens metabolized extensively by the intestinal microflora. Considerable important evidence is already available that shows extensive interindividual variation in isoflavone metabolism, and we have investigated the extent of this variation in a crossover study of a soy-containing food low or high in isoflavones (each treatment period lasted for 17 days, and the 2 treatment periods were separated by a 25-day washout period) in 24 healthy subjects [19 women and 5 men, mean age 30 yr, range 19-40, mean body mass index 22.5 +/- 3.5 (SD) kg/m2]. There was a 16-fold variation in total isoflavonoid excretion in urine after the high-isoflavone treatment period. The variation in urinary equol excretion was greatest (664-fold), and subjects fell into two groups: poor equol excretors and good equol excretors (36%). A significant negative correlation was found between the proportion of energy from fat in the habitual diet and urinary equol excretion (r = -0.55; p = 0.012). Good equol excretors consumed less fat as percentage of energy than poor excretors (26 +/- 2.3% compared with 35 +/- 1.6%, p < 0.01) and more carbohydrate as percentage of energy than poor excretors (55 +/- 2.9% compared with 47 +/- 1.7%, p < 0.05). Interindividual variation in the urinary excretion of O-desmethyl-angolensin (O-DMA) was also apparent (76-fold after the high-isoflavone treatment period), but there was no relationship between equol excretion and O-DMA excretion. Enterolactone was the major lignan metabolite in urine and plasma but showed less interindividual variation than equol and O-DMA. It is suggested that the dietary fat intake decreases the capacity of gut microbial flora to synthesize equol.

Adult↗

PubMed2000

Anti-carcinogenicity of probiotics and prebiotics.

Yoghurt, and the lactic acid producing bacteria (LAB; probiotics) that it contains, have received much attention as potential cancer-preventing agents in the diet. It is usually considered that the mechanism of the action is by increasing the numbers of LAB in the colon, which modifies the ability of the microflora to produce carcinogens. Prebiotics such as non-digestible oligosaccharides (NDO) appear to have similar effects on the microflora by selectively stimulating the growth of LAB in the colon. Evidence for cancer-preventing properties of pro- and prebiotics is derived from studies on faecal enzyme activities in animals and humans, inhibition of genotoxicity of known carcinogens in vitro and In vivo, suppression of carcinogen-induced preneoplastic lesions and tumours in laboratory animals. Some of these studies indicate that combinations of pro and prebiotics ('synbiotics') are more effective. Epidemiological and intervention studies provide some, albelt limited, evidence for protective effects of products containing probiotics in humans.

Animals↗

PubMed1999

Resistant starch modifies gut microflora and microbial metabolism in human flora-associated rats inoculated with faeces from Italian and UK donors.

The effect of sucrose and resistant starch ('CrystaLean'--a retrograded, amylose starch) on human gut microflora and associated parameters was studied in human flora-associated (HFA) rats, colonized with microfloras from UK or Italian subjects, to determine whether such floras were affected differently by dietary carbohydrates. Consumption of the resistant starch diet resulted in significant changes in four of the seven main groups of bacteria enumerated. In both the UK and Italian flora-associated rats, numbers of lactobacilli and bifidobacteria were increased 10-100-fold, and there was a concomitant decrease in enterobacteria when compared with sucrose-fed rats. The induced changes in caecal microflora of both HFA rat groups were reflected in changes in bacterial enzyme activities and caecal ammonia concentration. Although it had little effect on caecal short-chain fatty acid concentration, CrystaLean markedly increased the proportion of n-butyric acid in both rat groups and was associated with a significant increase in cell proliferation in the proximal colon of the Italian flora-associated rats. CrystaLean appeared to play a protective role in the colon environment, lowering caecal ammonia concentration, caecal pH and beta-glucuronidase activity.

Ammonia↗

PubMed1999

Effects of soy or rye supplementation of high-fat diets on colon tumour development in azoxymethane-treated rats.

Evidence is accumulating that a diet high in plant-derived foods may be protective against cancer. One class of plant component under increasing investigation is the phytoestrogens of which there are two main groups: the isoflavones, found mainly in soy products, and the lignans, which are more ubiquitous and are found in fruit, vegetables and cereals with high levels being found in flaxseed. In this study, we have used carefully balanced high-fat (40% energy) diets: a control diet (containing low isoflavone soy protein as the sole protein source), a rye diet (the control diet supplemented with rye bran) and a soy diet (containing as protein source a high isoflavone soy protein). The effect of these diets on the development of colonic cancer was studied in F-344 rats treated with the carcinogen, azoxymethane (two doses of 15 mg/kg given 1 week apart). Colons from treated animals were examined for aberrant crypt foci (ACF) and tumours after 12 and 31 weeks. Results after 12 weeks showed no differences in the total number of ACF in the control, soy or rye bran groups. However, the soy group had increased numbers of small ACF (less than four crypts/focus) while the rye group had decreased numbers of large ACF (greater than six crypts/focus). Examination of colons after 31 weeks gave similar low numbers of ACF in each group with no differences in multiplicity. There were no differences in the number of tumours between the control (1.36 tumours/rat) and soy (1.38 tumours/rat) groups. However, there was a significant decrease in the number of tumours in the rye group (0.17 tumours/rat). These results suggest that soy isoflavones have no effect on the frequency of colonic tumours in this model while rye bran supplementation decreases the frequency of colon cancer. This effect is due not to a decrease in early lesions but in their progression to larger multi-crypt ACF. The study also supports the hypothesis that larger ACF are more predictive of subsequent tumorigenicity.

Animals↗

PubMed1998

Effect of Bifidobacterium longum and inulin on gut bacterial metabolism and carcinogen-induced aberrant crypt foci in rats.

The effect of Bifidobacterium longum (4 x 10(8) viable cells/g diet) and a derivative of inulin ('Raftiline HP'; 5% w/w in diet) on colonic aberrant crypt foci (ACF) induced by the colon carcinogen azoxymethane (AOM) has been studied. The concentration of ammonia, a putative tumour promoter produced by bacterial degradation of protein and urea, and the activities of certain bacterial enzymes thought to play a role in colon carcinogenesis, beta-glucuronidase and beta-glucosidase were also assayed. Consumption of either B. longum or inulin was associated with a decrease (26 and 41%, respectively) in AOM-induced small ACF (i.e. those comprising 1-3 aberrant crypts per focus). Combined administration of the bifidobacterium and inulin resulted in more potent inhibition of ACF than administration of the two separately, achieving 80% inhibition of small ACF. Furthermore, the combined administration significantly decreased the incidence (by 59%) of large ACF (>4 aberrant crypts per focus), which are considered to be predictive of eventual tumour incidence. Since the dietary treatments were started 1 week after the carcinogen dose, the results suggest that B. longum and inulin may be affecting the early promotion phase of the carcinogenic process. Consumption of diets containing B. longum, inulin or both were also associated with decreases in beta-glucuronidase activity and ammonia concentration in the caecal contents. Both these factors have been associated with carcinogenesis of the colon in experimental animal models. In rats given inulin-containing diets (with or without B. longum) an increase in caecal wt and beta-glucosidase activity and a decrease in caecal pH were observed. The results suggest that consumption of B. longum or inulin was associated with potentially beneficial changes in caecal physiology and bacterial metabolic activity in relation to tumour risk and in the incidence of putative preneoplastic lesions in the colon. The results also indicated that combined treatment with the two agents was more effective in reducing colonic lesions.

Ammonia↗

PubMed1997

Influence of carcinogen binding by lactic acid-producing bacteria on tissue distribution and in vivo mutagenicity of dietary carcinogens.

The aims of this investigation were to determine whether viable cultures of lactic acid-producing organisms (LAB) can bind dietary carcinogens and to assess the consequences of binding for the absorption from the gut, distribution in the body and in vivo genotoxicity of ingested carcinogens. The carcinogens used in this study were ones known to be present in the human diet, namely benzo[a]pyrene (B(a)P, aflatoxin B1 (AFB1) and the cooked food carcinogens 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 5-phenyl-2-amino-1-methylimidazo [4,5-f]pyridine (PhIP) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). They represent a range of structural types so that the specificity of any binding effects could be addressed. Of the carcinogens tested, B(a)P and Trp-P-2 were bound most effectively by the two LAB strains Bifidobacterium longum and Lactobacillus acidophilus. AFB1 was poorly bound, while MeIQx, MeIQ, PhIP and IQ were bound to an intermediate degree. The extent of the binding of the heterocyclic amine carcinogens was dependent on the pH conditions during incubation and this effect was more apparent with B. longum than with L. acidophilus. Using the host-mediated assay (HMA), an in vivo bacterial mutation assay, it was demonstrated that the administration of bacterial cell suspensions of B. longum and L. acidophilus did not lead to a reduction in induced mutagenicity by MeIQ, MeIQx or Trp-P-2, detectable in the liver of treated mice compared with controls. The lack of a protective effect could not be attributed to a short period of contact between bacterial cells and mutagens, since similar results were obtained after preincubating bacteria and mutagens together at pH 5 for 50-60 min, to maximize the binding, before gavaging the mice. Lack of activity of B(a)P in the HMA prevented the determination of the effect of LAB on genotoxicity of the polycyclic aromatic hydrocarbon. However, it is clear from the radiolabel distribution study that the amount of the carcinogen entering the blood was not significantly reduced by B. longum administration. In addition, the amount of radiolabelled B(a)P that reached the target organs (liver, lungs and heart) was also not affected by the LAB administration. A similar lack of inhibitory effect of B. longum on blood concentration and accumulation in the liver of Trp-P-2 was apparent. The results of the present study suggest that although LAB may bind carcinogens in vitro, this does not lead to major changes in absorption and distribution of carcinogens in the body, or in their genotoxic activity in the liver.

Animals↗

PubMed1997

Effects of high- and low-risk diets on gut microflora-associated biomarkers of colon cancer in human flora-associated rats.

Formulated diets associated with a high risk (HR) or low risk (LR) for colon cancer were used to assess the effect of diet on putative metabolic biomarkers in human flora-associated rats: The HR diet was high in fat and sucrose and low in calcium and fiber; the LR diet was low in fat and high in starch, calcium, and fiber. The nutrient-to-energy ratio and energy intake were the same for both diets. Body and liver weights were significantly higher in animals fed the HR diet, possibly due to greater energy availability from fat. Cecal weights were significantly higher in animals fed the LR diet, presumably due to a bulking effect of the fiber and increased bacterial biomass. The HR diet significantly altered cecal bacterial enzyme activity: beta-glucuronidase activity increased 2.5-fold, and beta-glucosidase activity was halved. Ammonia production and the bacterial metabolism of 2-amino-3-methyl-7H-imidazo[4,5-f] quinoline (IQ) to 7-hydroxy-IQ (7OHIQ) were significantly higher in animals fed the HR diet. The HR diet, which contained factors common to diets consumed throughout the Western world, increased beta-glucuronidase activity, elevated cecal ammonia concentrations, and enhanced the genotoxic risk from 7OHIQ formation, three putative metabolic biomarkers of colorectal cancer. The significance of the reduction in beta-glucosidase is unclear.

Animals↗