Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.2.1.31 (beta-glucuronidase)
7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Supplementation of the human diet with prebiotic substances such as inulin and non-digestible oligosaccharides (NDO), e.g., galacto-oligosaccharides (GOS), has been associated with various health benefits. However, little information is available regarding the spatial location of their metabolism in human gut bacterial ecosystems. Therefore, the present study investigated the metabolism of inulin and GOS with respect to bacterial growth, bifidobacterial stimulatory properties and anti-mutagenicity potential, in a three-stage continuous culture model of the colon which reproduces the physicochemical characteristics of the proximal (V1) and distal (V2, V3) colons. Fermentation of both carbohydrates was rapid, and occurred primarily in V1, as evidenced by acid formation. Inulin metabolism was associated with 10-fold stimulation of lactobacillus populations, together with smaller increases in bifidobacterial cell counts in V1. However, peptostreptococci, enterococci and Clostridium perfringens also increased in this fermentation vessel. In contrast, GOS was only weakly bifidogenic in V1, although these bacteria did proliferate in V2. GOS also increased lactobacilli by an order of magnitude in V1. However, overall changes in microbial populations resulting from inulin or GOS addition were minimal in V2 and V3. Potential beneficial effects of inulin metabolism included minor reductions in beta-glucosidase and beta-glucuronidase, whereas GOS strongly suppressed these enzymes, together with arylsulphatase (AS). Growth of putatively health promoting micro-organisms was not only associated with reductions in enzymes linked to genotoxicity. For example, both carbohydrates stimulated synthesis of nitroreductase and azoreductase, throughout the fermentation system, while inulin increased AS. Colonic transit time is an important factor in bacterial metabolism in the large bowel, and these data suggest that, in some circumstances, NDO fermentation will occurprincipally in the proximal colon.
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PMID:Modulation of genotoxic enzyme activities by non-digestible oligosaccharide metabolism in in-vitro human gut bacterial ecosystems. 1154 86

Many non-steroidal anti-inflammatory drugs (NSAIDs) which form acyl glucuronide conjugates as major metabolites have shown an antiproliferative effect on colorectal tumors. This study assesses the extent to which rearrangement of an acyl glucuronide metabolite of a model NSAID into beta-glucuronidase-resistant isomers facilitates its passage through the small intestine to reach the colon. Rats were dosed orally with diflunisal (DF), its acyl glucuronide (DAG) and a mixture of rearrangement isomers (iso-DAG) at 10 mg DF equivalents/kg. The parent drug DF appeared in plasma after all doses, with maximum concentrations of 20.5+/-2.5, 28.8+/-8.3 and 11.0+/-1.6 microg DF/ml respectively, obtained at 3.8+/-0.3, 3.6+/-1.8 and 7.5+/-0.9 hr after the DF, DAG and iso-DAG doses respectively. At 48 hr, 16.2+/-3.3, 19.8+/-0.8 and 42.9+/-10.1% of the doses respectively were recovered in feces, with < or = 1% remaining in the intestine. About half of each dose was recovered as DF and metabolites in 48 hr urine: for DF and DAG doses, the majority was in the first 24 hr urine, whereas for iso-DAG doses, recoveries in the first and second 24 hr periods were similar. The results show that hydrolysis of both DAG and iso-DAG, and absorption of liberated DF, occur during passage through the gut, but that these processes occur more slowly and to a lesser degree for iso-DAG. The intrinsic hydrolytic capacities of various intestinal segments (including contents) towards DAG and iso-DAG were obtained by incubating homogenates under saturating concentrations of DAG/iso-DAG at 37 degrees C. Upper small intestine, lower small intestine, caecum and colon released 2400, 3200, 9200 and 22800 microg DF/hr/g tissue plus contents respectively from DAG substrate, and 18, 10, 140 and 120 microg DF/hr/g tissue plus contents respectively from iso-DAG substrate. The much greater resistance of iso-DAG to hydrolysis appears attributable to its resistance to beta-glucuronidases. The data suggest that in rats dosed with DF, DAG excreted in bile would be substantially hydrolysed in the small intestine and liberated DF reabsorbed, but that portion which rearranges to iso-DAG would likely reach the colon.
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PMID:Rearrangement of diflunisal acyl glucuronide into its beta-glucuronidase-resistant isomers facilitates transport through the small intestine to the colon of the rat. 1176 4

A helper-dependent expression system based on transmissible gastroenteritis coronavirus (TGEV) has been developed using a minigenome of 3.9 kb (M39). Expression of the reporter gene beta-glucuronidase (GUS) (2-8 microg per 10(6) cells) and the porcine respiratory and reproductive syndrome virus (PRRSV) ORF5 (1-2 microg per 10(6) cells) has been shown using a TGEV-derived minigenome. GUS expression levels increased about eightfold with the m.o.i. and were maintained for more than eight passages in cell culture. Nevertheless, instability of the GUS and ORF5 subgenomic mRNAs was observed from passages five and four, respectively. About a quarter of the cells in culture expressing the helper virus also produced the reporter gene as determined by studying GUS mRNA production by in situ hybridization or immunodetection to visualize the protein synthesized. Expression of GUS was detected in the lungs, but not in the gut, of swine immunized with the virus vector. Around a quarter of lung cells showing replication of the helper virus were also positive for the reporter gene. Interestingly, strong humoral immune responses to both GUS and PRRSV ORF5 were induced in swine with this virus vector. The large cloning capacity and the tissue specificity of the TGEV-derived minigenomes suggest that these virus vectors are very promising for vaccine development.
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PMID:In vitro and in vivo expression of foreign genes by transmissible gastroenteritis coronavirus-derived minigenomes. 1184 52

Inflammatory bowel disease refers to ulcerative colitis and Crohn's disease, two gut diseases with unknown causes. The dramatic increase in the last half century and the big difference in incidence for people with the same ethnic background but living in different areas strongly suggested that environmental factors played the dominant role for these diseases. The similarity in many aspects for these two diseases suggested a common causative factor. Here I suggest the impaired inactivation of digestive proteases by deconjugated bilirubin, as the result of the inhibition of bilirubin deconjugation enzyme, beta-glucuronidase, originated from the luminal bacteria and mucosa of the gut, to be a possible mechanism for both ulcerative colitis and Crohn's diseases. I also provide evidence to suggest that saccharin could be the causative or one of the most important risk factors for inflammatory bowel disease as for its inhibition on beta-glucuronidase in the intestine.
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PMID:Impaired inactivation of digestive proteases by deconjugated bilirubin: the possible mechanism for inflammatory bowel disease. 1220 2

We investigated the chemoprotective effects of four common constituents of the human diet, i.e. a fermented milk, inulin, oligofructose and Brussels sprouts, towards 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced genotoxicity in male Fischer 344 rats harbouring a human intestinal microflora. We found that the four dietary components significantly reduced IQ-induced DNA damage in hepatocytes (reduction ranged from 74% with inulin to 39% with Brussels sprouts) and colonocytes (reduction ranged from 68% with inulin to 56% with Brussels sprouts). This chemoprotective effect correlated with the induction of hepatic UDP-glucuronosyl transferase following Brussels sprouts consumption, and with alterations of bacterial metabolism in the distal gut (acidification, increase of butyrate proportion, decrease of beta-glucuronidase activity) following inulin consumption.
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PMID:Protective effects of Brussels sprouts, oligosaccharides and fermented milk towards 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced genotoxicity in the human flora associated F344 rat: role of xenobiotic metabolising enzymes and intestinal microflora. 1503 16

Yoghurt feeding inhibits induced colon cancer in mice. Several studies showed the immunomodulatory effect of yoghurt which can explain this inhibition. It is possible that yoghurt bacteria can also affect gut flora enzymes related to colon carcinogenesis as reported for other probiotics in different animal tumours. The aim of this work was to evaluate the role of yoghurt starter bacteria and their cell-free fermentation products on the reduction of procarcinogen enzyme activities (beta-glucuronidase and nitroreductase). Mice injected with 1,2-dimethylhydrazine (DMH) and fed with yoghurt were used for this study. Mice given milk or yoghurt supernatant (cell free extract) were used to evaluate if the yoghurt antitumour effect is due to the starter bacteria or other components released during fermentation, that could inhibit these enzymes. We determined that yoghurt by itself maintained enzymes activities similar or lower than non-treatment control group, and the enzyme activity was also lower than milk or yoghurt supernatant groups. DMH increased the activity of the enzymes. Mice injected with DMH and fed cyclically with yoghurt presented lower enzymes activities than the tumour control group. Feeding yoghurt decreased procarcinogenic enzyme levels in the large intestine contents of mice bearing colon tumour. The results of this study provide another mechanism by which yoghurt starter bacteria interact with the large intestine of the mice and prevent colon cancer.
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PMID:Reduction of beta-glucuronidase and nitroreductase activity by yoghurt in a murine colon cancer model. 1595 63

beta-Glucuronidase activity (encoded by the gus gene) has been characterized for the first time from Ruminococcus gnavus E1, an anaerobic bacterium belonging to the dominant human gut microbiota. beta-Glucuronidase activity plays a major role in the generation of toxic and carcinogenic metabolites in the large intestine, as well as in the absorption and enterohepatic circulation of many aglycone residues with protective effects, such as lignans, flavonoids, ceramide and glycyrrhetinic acid, that are liberated by the hydrolysis of the corresponding glucuronides. The complete nucleotide sequence of a 4537 bp DNA fragment containing the beta-glucuronidase locus from R. gnavus E1 was determined. Five ORFs were detected on this fragment: three complete ORFs (ORF2, gus and ORF3) and two partial ORFs (ORF4 and ORF5). The products of ORF2 and ORF3 show strong similarities with many beta-glucoside permeases of the phosphoenolpyruvate : beta-glucoside phosphotransferase systems (PTSs), such as Escherichia coli BglC, Bacillus subtilis BglP and Bacillus halodurans PTS Enzyme II. The product of ORF5 presents strong similarities with the amino-terminal domain of Clostridium acetobutylicum beta-glucosidase (bglA). The gus gene product presents similarities with several known beta-glucuronidase enzymes, including those of Lactobacillus gasseri (69%), E. coli (61%), Clostridium perfringens (59%) and Staphylococcus aureus (58%). By complementing an E. coli strain in which the uidA gene encoding the enzyme was deleted, it was confirmed that the R. gnavus gus gene encodes the beta-glucuronidase enzyme. Moreover, it was found that the gus gene was transcribed as part of an operon that includes ORF2, ORF3 and ORF5.
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PMID:Genetic characterization of the beta-glucuronidase enzyme from a human intestinal bacterium, Ruminococcus gnavus. 1600 Jul 22

Butyrivibrio fibrisolvens, a butyrate-producing ruminal bacterium, was evaluated for use as a probiotic to prevent colorectal cancer. Oral administration to Jcl:ICR mice of a new strain of B. fibrisolvens (MDT-1) that produces butyrate at a high rate (10(9) cfu/dose) increased the rate of butyrate production by fecal microbes, suggesting that MDT-1 can grow in the gut. The number of colorectal aberrant crypt foci (ACF), putative preneoplastic lesions induced by 1,2-dimethylhydrazine, was reduced after MDT-1 administration (10(9) cfu/dose, 3 times/wk for 4 wk). The number of aberrant crypts (ACs), number of foci having 3 or 4 ACs per focus, and the percentage of mice having 3 or 4 ACs per focus were also reduced, suggesting that the progress of lesions was suppressed by MDT-1. Interestingly, the MDT-1 cell homogenate did not have a similar beneficial effect. MDT-1 had low beta-glucuronidase activity, and administration of MDT-1 reduced the beta-glucuronidase activity in the colorectal contents. The numbers of natural killer (NK) and NKT cells in the spleen were markedly enhanced in response to MDT-1. Decreased beta-glucuronidase activity and increased numbers of NK and NKT cells and butyrate production may explain in part why MDT-1 administration suppressed ACF formation. These results suggest that colorectal cancer may be prevented or suppressed by the utilization of MDT-1 as a probiotic. Administration of MDT-1 had no harmful effect on the health of mice at least for 3 mo.
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PMID:Oral administration of butyrivibrio fibrisolvens, a butyrate-producing bacterium, decreases the formation of aberrant crypt foci in the colon and rectum of mice. 1631 36

The safety assessment of Bifidobacterium longum SPM1205 isolated from healthy Koreans and this strain's inhibitory effects on fecal harmful enzymes of intestinal microflora were investigated. The overall safety of this strain was investigated during a feeding trial. Groups of SD rats were orally administered a test strain or commercial reference strain B. longum 1 x 10(9) CFU/kg body weight/day for four weeks. Throughout this time, their feed intake, water intake and live body weight were monitored. Fecal samples were periodically collected to test harmful enzyme activities of intestinal microflora. At the end of the four-week observation period, samples of blood, liver, spleen, kidney, and gut tissues were collected to determine for hematological parameters and histological differences. The results obtained in this experiment demonstrated that four weeks of consumption of this Bifidobacterium strain had no adverse effects on rat's general health status, blood biochemical parameters or histology. Therefore, it is likely to be safe for human use. Fecal harmful enzymes such as beta-glucosidase, beta-glucuronidase, tryptophanase and urease, were effectively inhibited during the administration of the B. longum SPM1205. These results suggested that this B. longum SPM 1205 could be used for humans as a probiotic strain.
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PMID:Safety assessment of potential lactic acid bacteria Bifidobacterium longum SPM1205 isolated from healthy Koreans. 1641 Jul 64

Due to its low digestibility in the small intestine, a major fraction of the polyol isomalt reaches the colon. However, little is known about effects on the intestinal microflora. During two 4-week periods in a double-blind, placebo-controlled, cross-over design, nineteen healthy volunteers consumed a controlled basal diet enriched with either 30 g isomalt or 30 g sucrose daily. Stools were collected at the end of each test phase and various microbiological and luminal markers were analysed. Fermentation characteristics of isomalt were also investigated in vitro. Microbiological analyses of faecal samples indicated a shift of the gut flora towards an increase of bifidobacteria following consumption of the isomalt diet compared with the sucrose diet (P<0.05). During the isomalt phase, the activity of bacterial beta-glucosidase decreased (P<0.05) whereas beta-glucuronidase, sulfatase, nitroreductase and urease remained unchanged. Faecal polyamines were not different between test periods with the exception of cadaverine, which showed a trend towards a lower concentration following isomalt (P=0.055). Faecal SCFA, lactate, bile acids, neutral sterols, N, NH3, phenol and p-cresol were not affected by isomalt consumption. In vitro, isomalt was metabolized in several bifidobacteria strains and yielded high butyrate concentrations. Isomalt, which is used widely as a low-glycaemic and low-energy sweetener, has to be considered a prebiotic carbohydrate that might contribute to a healthy luminal environment of the colonic mucosa.
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PMID:Effect of isomalt consumption on faecal microflora and colonic metabolism in healthy volunteers. 1644 15


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