Role of gut bacteria in human toxicology and pharmacology

Cover Page......Page 1
Title Page......Page 3
ISBN 0748401105......Page 4
1. The normal gut bacterial flora......Page 5
3. The use of gnotobiotic animals in studies of toxicology......Page 6
5 Nitrate pharmacology and toxicology......Page 7
7 Metabolism of nitrogen compounds: miscellaneous compounds......Page 8
9 Toxicology of butyrate and short-chain fatty acids......Page 9
11 Interactions between fat substitutes and gut bacteria......Page 10
13. Sulphate-reducing bacteria (SRB)......Page 11
15. Vitamin K and selected water-soluble vitamins: roles of the gut bacteria in nutrition and pharmacology......Page 12
16. Factors governing biliary excretion......Page 13
18. Influence of the probiotics, lactobacilli and bifidobacteria on gastrointestinal disorders in adults......Page 14
Index......Page 15
Introduction......Page 16
References......Page 17
D.C.Ellwood......Page 18
B.J.Moran......Page 19
T.G.Schlagheck......Page 20
J.H.P.Watson......Page 21
Section 1 Gut bacteriology......Page 22
1.2.1 Sampling problems......Page 23
1.2.2 Cultivation problems......Page 24
1.3.2 Flora of the stomach......Page 25
1.3.4 Flora of the lower ileum......Page 29
1.3.6 The colonic mucosal flora......Page 30
1.4 Factors controlling the gut flora composition......Page 31
1.4.1 pH......Page 32
1.4.2 Nutrient supply......Page 33
1.4.5 Facultative anaerobes......Page 34
1.4.8 Relevance to the human gut......Page 35
1.5.1 Bacteriophage......Page 36
1.6.1 Lysozyme......Page 37
References......Page 38
2.2.1 Methods of assay—pure strains versus caecal contents......Page 40
2.2.2 Methods of expressing the data......Page 41
2.3 Effect of diet on faecal enzyme activity......Page 42
2.3.2 Specific substrate supply......Page 43
2.3.3 Induction of specific enzymes......Page 44
2.4 Relevance to toxicological studies......Page 45
References......Page 46
3.1 Introduction......Page 47
3.2.2 Characteristics of germ-free animals......Page 48
3.3.1 Metabolism of xenobiotics......Page 49
3.3.2 Secondary effects of the presence of the flora......Page 51
3.4 The human-flora-associated (HFA) rat......Page 52
3.5 Comments and conclusions......Page 53
References......Page 54
Section 2 Nitrogen metabolism......Page 58
4.1 Introduction......Page 59
4.1.1 Nitrogen as an element essential for life......Page 60
4.2 Nitrogen balance, amino acid flux and protein turnover......Page 61
4.3 Urea hydrolysis......Page 64
4.4 Role of microflora......Page 66
4.5 Colonic nitrogen metabolism......Page 67
4.5.1 Source of colonic urea......Page 69
4.6 Destiny of hydrolyzed urea nitrogen in the colon......Page 70
4.7 Adaptation to suboptimal protein intakes is dependent on an intact urea-nitrogen salvage mechanism......Page 71
4.8 Clinical implications of the salvage of urea nitrogen......Page 72
4.9 Conclusion......Page 74
References......Page 75
5.2 Pharmacology......Page 80
5.3.1 Short-term/acute effects......Page 81
5.3.2 Long-term/chronic effects......Page 82
5.4.1 Nitrate metabolism......Page 83
5.4.2 Nitrite metabolism......Page 84
References......Page 85
6.1 Introduction......Page 90
6.3 N-nitrosation involving gaseous nitrogen oxides......Page 92
6.4 N-nitrosation involving bacterial enzyme systems......Page 93
6.5 N-nitrosation involving mammalian enzyme systems......Page 96
References......Page 97
7.2.1 Introduction......Page 101
7.2.2 Bacterial azoreductase......Page 103
7.2.3 Factors affecting in vivo activity......Page 104
7.2.4 Toxicological consequences......Page 105
7.3.2 Gut bacterial nitro reductase......Page 106
7.3.3 Reduction of environmental contaminants......Page 107
7.4.2 Amino acid decarboxylase......Page 108
7.4.3 Toxicological significance......Page 109
7.5.3 Pharmacological significance......Page 110
7.6.2 Tyrosine metabolism......Page 111
7.6.3 Tryptophan metabolism......Page 112
References......Page 113
Section 3 Carbohydrate metabolism......Page 116
8.2 Monosaccharide metabolism......Page 117
8.3 Glycosidases......Page 118
8.3.2 β-glucosidase......Page 119
8.4 Polysaccharide breakdown......Page 121
8.4.2 Dietary fibre......Page 122
8.5 Toxicological importance of polysaccharide degradation......Page 124
References......Page 125
9.2 Butyrate as both metabolic fuel and inducer of differentiation......Page 127
9.4 Acetylation neutralizes positive charges at the N-terminal domains of core histones......Page 130
9.5 The impact of the butyrate signal on chromatin structure......Page 131
9.6 Hyperacetylation and arrest of the cell cycle......Page 134
9.7 Butyrate and activation of gene expression......Page 136
9.8 Butyrate and inhibition of gene expression......Page 137
9.9 Butyrate and human colon cancer cell lines......Page 139
9.10 Butyrate and various other transformed cell lines......Page 140
9.12 Butyrate and cancerogenesis in vivo......Page 142
9.13 Butyrate and intestinal cells in vivo......Page 143
9.14 Short-chain fatty acids and human diseases other than cancer......Page 144
References......Page 145
Section 4 Fat metabolism......Page 150
10.1 Introduction......Page 151
10.2 Fat digestion......Page 152
10.2.1 Metabolism of fats and phospholipids......Page 153
10.4 Bacterial metabolism of bile salts......Page 155
10.4.1 Cholylglycine hydrolase......Page 156
10.4.2 7-Dehydroxylase......Page 157
10.4.3 Hydroxysteroid dehydrogenases......Page 159
10.4.4 Toxicological consequences of bile acid metabolism......Page 160
References......Page 161
11.1 Fat substitutes......Page 163
11.2.2 Metabolism of fat substitutes......Page 164
11.2.3 Effects on normal microflora function and activity......Page 165
11.3.1 Approaches for assessing the microbial metabolism of fat substitutes......Page 166
11.3.2 Definitive studies on the metabolism of olestra......Page 167
11.4 Effect of fat substitutes on microbial metabolism......Page 168
11.5.1 Microbial fermentation......Page 169
11.5.2 Microbial bioconversions......Page 170
11.7 Metabolism of enterohepatically circulating steroid hormones......Page 173
11.7.2 Microbial metabolism of xenobiotics......Page 174
11.9 Faecal microflora composition......Page 175
References......Page 176
Section 5 Sulphur metabolism......Page 179
12.2 Delivery of the sulphur compound to the intestinal bacteria......Page 180
12.2.1 Oral delivery......Page 182
12.2.3 Secretion into the gut lumen......Page 183
12.3.1 Reduction reactions......Page 185
12.3.2 Hydrolysis reactions......Page 190
References......Page 198
13.1 Introduction......Page 206
13.3 Presence of SRB in human faeces......Page 207
13.4 SRB and heavy metal pharmacology......Page 210
References......Page 211
Section 6 Metabolism of miscellaneous compounds......Page 213
14.2 Effect of iron on the intestinal microflora......Page 214
14.3 Role of the gut flora in the metabolism of toxic metals......Page 215
14.4.2 In vitro metabolism of arsenicals by the gut flora......Page 216
14.4.4 Microbial metabolism of other arsenicals......Page 217
14.5.1 Chemical forms, exposure and toxic effects......Page 218
14.5.2 Metabolism of mercury compounds by gut bacteria......Page 219
14.5.4 Implications of bacterial demethylation of MeHg......Page 223
14.6 Conclusions......Page 225
References......Page 226
15.1 Introduction......Page 230
15.2 Vitamin K......Page 231
15.2.1 Gut bacteria as a source of vitamin K......Page 232
15.2.2 Vitamin K absorption......Page 233
15.2.3 Human infants......Page 235
15.2.4 Effects of drugs and vitamin K nutrition......Page 236
15.3 Biotin......Page 237
15.3.1 Gut bacteria and biotin supply......Page 238
15.4 Vitamin B12......Page 239
15.5 Folic acid......Page 240
15.6.1 Gut bacteria and riboflavin supply......Page 241
References......Page 242
Section 7 Biliary excretion and enterohepatic circulation......Page 246
16.1 General aspects of bile formation and enterohepatic cycling......Page 247
16.3 Composition of bile......Page 248
16.4 Generation of bile flow......Page 249
16.5 Experimental procedures for studying bile formation......Page 250
16.7 Sinusoidal uptake......Page 251
16.8 Intracellular movements and metabolism......Page 252
16.9 Canalicular secretory processes......Page 254
16.10 Retention of components in the biliary tree: biliary versus renal excretion......Page 255
16.12 Conjugation of native or biotransformed molecules as a determinant of biliary secretion: biliary versus renal excretion......Page 256
Acknowledgements......Page 257
References......Page 258
17.2 Role of microfloral metabolism in EHC and species differences......Page 260
17.3 The influence of EHC on pharmacokinetics and persistence......Page 264
17.5 Influence of EHC on toxicity......Page 267
17.6 Influence of EHC on carcinogenesis......Page 268
Acknowledgements......Page 270
References......Page 271
Section 8 Probiotics......Page 276
18.1 Introduction......Page 277
18.3 Bifidobacteria......Page 278
18.5 Survival of ingested probiotics in the gastrointestinal tract......Page 279
18.6.1 Disturbances in the protective flora......Page 280
18.7.2 Attempts to re-establish the microflora, after treatment with antimicrobial agents......Page 281
18.7.3 Clostridium difficile diarrhoea and pseudomembranous colitis......Page 283
18.7.5 Enteritis......Page 284
18.7.8 Radiation therapy......Page 285
18.7.11 Lactose intolerance......Page 286
18.7.12 Antimutagenic and anticarcinogenic effects......Page 287
18.7.13 Liver cirrhosis and hepatic encephalopathy......Page 290
References......Page 291
Index......Page 298