Techniques for microfloral and associated metabolic studies in relation to the absorption and enterohepatic circulation of drugs

Illing, H. Paul A.

doi:10.3109/00498258109045319

Cited by 29 publications

(9 citation statements)

References 50 publications

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“…Back et al [56,57] showed that enterohepatic circulation of norethisterone glucuronide and sulfate conjugates was strongly reduced in rats after treatment with ampicillin, eliminating the anaerobic flora. Studies before 1980 dealing with the role of the microflora in the absorption and enterohepatic circulation of drugs were critically reviewed by Illing [58].…”

Section: Discussionmentioning

confidence: 99%

Hydrolysis of iodothyronine conjugates by intestinal bacteria

Hazenberg¹,

Herder

Visser

1988

FEMS Microbiology Letters

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Glucuronide and sulfate conjugation are important pathways in the peripheral metabolism of thyroid hormone. These reactions occur predominantly in the liver, and especially the glucuronides are excreted in the bile. Although an enterohepatic circulation after intestinal hydrolysis of iodothyronine conjugates is suggested by several authors, substantial proof has not been presented so far. In the present paper experimental work from our group is reviewed. The studies showed that fecal suspensions of human or rat origin hydrolysed iodothyronine conjugates, whereas oral administration of antibiotics to rats strongly reduced this capacity. Obligately anaerobic intestinal bacteria were found to be responsible for the hydrolysis and several species belonging to the major residents of the intestinal flora of man and rat could be isolated and identified. Recent studies with conventional and decontaminated rats produced strong support for the existence of an enterohepatic circulation of thyroid hormone. Our findings are discussed in connection with other relevant studies on this subject.

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Section: Discussionmentioning

confidence: 99%

Hydrolysis of iodothyronine conjugates by intestinal bacteria

Hazenberg¹,

Herder

Visser

1988

FEMS Microbiology Letters

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“…However, for the drug metabolism and toxicology communities, despite many early studies showing its importance in some instances of xenobiotic biotransformation (e.g., see refs4,5), the gut microbiota have not been a focus. Nevertheless, increased awareness is important not only because the microbiota perform a range of important metabolic reactions but because the gut microbiome also represents a source of physiological variability between both individuals and populations.…”

Section: Introductionmentioning

confidence: 99%

Gut microbiome interactions with drug metabolism, efficacy, and toxicity

Wilson

Nicholson

2017

Translational Research

486

327

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The gut microbiota have both direct and indirect effects on drug and xenobiotic metabolism and this can have consequences for both efficacy and toxicity. Indeed microbiome-driven drug metabolism is essential for the activation of certain prodrugs such as e.g., azo drugs such as prontosil and neoprontosil resulting in the release of sulphanilamide. In addition to providing a major source of reductive metabolizing capability the gut microbiota provide a suite of additional reactions including acetylation/deacylation decarboxylation, dehydroxylation, demethylation, dehalogenation and importantly, in the context of certain types of drug-related toxicity, conjugate hydrolysis reactions. In addition to direct effects the gut microbiota can affect drug metabolism and toxicity indirectly via e.g., the modulation of host drug metabolism and disposition and competition of bacterial-derived metabolites for xenobiotic metabolism pathways. And, of course, the therapeutic drugs themselves can have effects, both intended and unwanted, which can impact on the health and composition of the gut microbiota with unforeseen consequences.

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“…The role of the gut microbiota in modulating the response of humans and animals to drugs was once an active field of research (e.g., see [3][4][5][6][7][8][9]) but this topic has been somewhat neglected in recent years, by both academia and the pharmaceutical industry, though interestingly not by food scientists and those interested in the effects of pharmacologically-active dietary constituents. However, for the drug metabolism community it is arguable that the gut microbiota of animals and man represents a largely forgotten organ of drug metabolism and disposition.…”

Section: Introductionmentioning

confidence: 99%

The Role of Gut Microbiota in Drug Response

Wilson¹,

Nicholson²

2009

CPD

104

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Higher organisms such as mammals exist in a symbiotic relationship with their gut microbiota, formed from a diverse and highly metabolically active consortium of species. The gut microbiota, in addition to their ability to process dietary derived material, are also capable of performing a range of biotransformations on xenobiotics, such as drugs and their metabolites, in ways that can affect absorption and bioavailability. The potential for the gut microflora to influence drug metabolism and toxicity in unexpected ways is discussed.

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Techniques for microfloral and associated metabolic studies in relation to the absorption and enterohepatic circulation of drugs

Cited by 29 publications

References 50 publications

Hydrolysis of iodothyronine conjugates by intestinal bacteria

Hydrolysis of iodothyronine conjugates by intestinal bacteria

Gut microbiome interactions with drug metabolism, efficacy, and toxicity

The Role of Gut Microbiota in Drug Response

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