**Author details**

*Human Microbiome*

genome; therefore, enzymes of these microbes are involved in many biochemical processes, i.e., metabolism of xenobiotics (compounds not produced in human host, e.g., drugs and pollutants) and dietary sources. Metabolites produced by gut microbiome play significant roles in human health and diseases; these metabolites include short-chain fatty acids such as butyrate (**11**), as well as other metabolites, e.g., nicotinamide (**12**), 5-aminovaleric acid (**14**), and taurine (**15**) (see Section 2). Since gut microbiome and its metabolites substantially contribute to human health and diseases, a therapy by intervention strategies using gut microbiota can potentially be useful for some diseases, for example, metabolic disorders, cardiovascular disease, food allergy, and neurological disorders. Supplementation with probiotics or certain gut bacteria, as well as their metabolites, may be a new therapeutic method in the future. Fecal microbiota transplantation, e.g., transferring gut bacteria from healthy

individuals into patients, is a challenging research study in the near future.

Gut microbiome can metabolite commonly used drugs and natural products. Drug metabolism by gut microorganisms decreases the levels of drugs in serum, thus disturbing the drug pharmacokinetics, which can lead to alteration of therapeutic efficiency. Moreover, metabolites produced by the drug metabolism of gut microbiome contribute considerably to the drug efficacy. For example, the levels of the drug L-dopa (**56**) are substantially reduced by the metabolic activity of gut microbiome, and this results in the requirement of higher doses for the Parkinson's patients with gut microbiome that has high metabolic activity toward the drug L-dopa (**56**) (see Section 3.1). This example well demonstrates the role of gut microorganisms on treatment outcomes of the commonly used drugs. Gut microbiome could improve many drug therapies, for example, cancer immunotherapy targeting CTLA-4 blockade and immune checkpoint inhibitor via the PD-1/PD-L1 pathway. Moreover, the metabolism of gut microbiome improves drug efficacy because it assists the bioconversion of some drugs into their active forms, for example, a biotransformation of lovastatin (**98**) to its active form, hydroxy acid-lovastatin (**101**), and a bioconversion of aspirin (**70**) to salicylic acid (**71**) that actively reduces pain. Interestingly, gut microbiome involves in a biotransformation of an alkaloid natural product berberine (**78**) to an absorbable form, dihydroberberine (**80**), which is absorbed at the intestine system (see Section 3.2). This result demonstrates that gut microbiome facilitates drug delivery of berberine (**78**) that has poor solubility by a biotransformation to an absorbable form, dihydroberberine (**80**), which is in turn converted to its active form berberine (**78**) in the human body. Since gut microbiome plays many important roles in drugs and natural products, the metabolism of natural products and drug candidates by gut microbiome should therefore be studied, and it should be a part of the drug development process. Gut microbiome can potentially play a crucial role for the improvement of

The author thanks the Center of Excellence on Environmental Health and

Development Office (PERDO), Ministry of Education, for the support of research

Toxicology, Science & Technology Postgraduate Education and Research

The author declares no competing interests or no conflict of interest.

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drug safety and efficacy.

**Acknowledgements**

**Conflict of interest**

that leads to this book chapter.

Prasat Kittakoop1,2,3

1 Chulabhorn Graduate Institute, Program in Chemical Sciences, Chulabhorn Royal Academy, Bangkok, Thailand

2 Chulabhorn Research Institute, Bangkok, Thailand

3 Center of Excellence on Environmental Health and Toxicology (EHT), CHE, Ministry of Education, Thailand

\*Address all correspondence to: prasat@cri.or.th

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
