Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (769 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Xenobiotic.
Where it fits in the MeSH classification
- Broader topics
- Pharmaceutical Preparations
Research landscape
PubMed indexes 8,350 records tagged with the MeSH heading “Xenobiotics” (counts retrieved 2026-10-31). 1,124 of them (13.5%) were published from 2020 onward, and the busiest period so far is 2000-2009 with 3,014 records.
Reviews account for 2,748 records (32.9%) and meta-analyses for 16. Randomized controlled trials number 9 (0.1%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 1,767 |
| 2000-2009 | 3,014 |
| 2010-2019 | 2,445 |
| 2020 onward | 1,124 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 2,748 | 32.9% |
| Meta-analyses | 16 | 0.2% |
| Randomized controlled trials | 9 | 0.1% |
Method: PubMed query "Xenobiotics"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Comparative Toxicogenomics Database (CTD): update 2021 | 2021 | Research article Design not recorded in structured metadata | 829 | cc by PMID 33068428 · DOI · PMC7779006 |
| Chemical transformation of xenobiotics by the human gut microbiota | 2017 | Review article Design not recorded in structured metadata | 795 | cc by PMID 28642381 · DOI · PMC5534341 |
| Cytochrome P450 Enzymes and Drug Metabolism in Humans | 2021 | Review article Design not recorded in structured metadata | 671 | cc by PMID 34884615 · DOI · PMC8657965 |
| Nutrient environment improves drug metabolic activity in human iPSC-derived hepatocytes and HepG2 | 2025 | Research article Design not recorded in structured metadata | 13 | cc by PMID 40794106 · DOI · PMC12477091 |
Comparative Toxicogenomics Database (CTD): update 2021 [1]
Abstract reading summary — source excerpts
- Opening excerpt
- The public Comparative Toxicogenomics Database (CTD; http://ctdbase.
- Closing excerpt
- Together, these updates continue to augment CTD as a powerful resource for generating testable hypotheses about the etiologies and molecular mechanisms underlying environmentally influenced diseases.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (200 words)
The public Comparative Toxicogenomics Database (CTD; http://ctdbase.org/) is an innovative digital ecosystem that relates toxicological information for chemicals, genes, phenotypes, diseases, and exposures to advance understanding about human health. Literature-based, manually curated interactions are integrated to create a knowledgebase that harmonizes cross-species heterogeneous data for chemical exposures and their biological repercussions. In this biennial update, we report a 20% increase in CTD curated content and now provide 45 million toxicogenomic relationships for over 16 300 chemicals, 51 300 genes, 5500 phenotypes, 7200 diseases and 163 000 exposure events, from 600 comparative species. Furthermore, we increase the functionality of chemical-phenotype content with new data-tabs on CTD Disease pages (to help fill in knowledge gaps for environmental health) and new phenotype search parameters (for Batch Query and Venn analysis tools). As well, we introduce new CTD Anatomy pages that allow users to uniquely explore and analyze chemical-phenotype interactions from an anatomical perspective. Finally, we have enhanced CTD Chemical pages with new literature-based chemical synonyms (to improve querying) and added 1600 amino acid-based compounds (to increase chemical landscape). Together, these updates continue to augment CTD as a powerful resource for generating testable hypotheses about the etiologies and molecular mechanisms underlying environmentally influenced diseases.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 33068428 · DOI · PMC7779006
Chemical transformation of xenobiotics by the human gut microbiota [2]
Abstract reading summary — source excerpts
- Opening excerpt
- The human gut microbiota makes key contributions to the metabolism of ingested compounds (xenobiotics), transforming hundreds of dietary components, industrial chemicals, and pharmaceuticals into metabolites with altered activities, toxicities, and lifetimes within the body.
- Closing excerpt
- Ultimately, a molecular understanding of gut microbial xenobiotic metabolism will guide personalized medicine and nutrition, inform toxicology risk assessment, and improve drug discovery and development.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (124 words)
The human gut microbiota makes key contributions to the metabolism of ingested compounds (xenobiotics), transforming hundreds of dietary components, industrial chemicals, and pharmaceuticals into metabolites with altered activities, toxicities, and lifetimes within the body. The chemistry of gut microbial xenobiotic metabolism is often distinct from that of host enzymes. Despite their important consequences for human biology, the gut microbes, genes, and enzymes involved in xenobiotic metabolism are poorly understood. Linking these microbial transformations to enzymes and elucidating their biological effects is undoubtedly challenging. However, recent studies demonstrate that integrating traditional and emerging technologies can enable progress toward this goal. Ultimately, a molecular understanding of gut microbial xenobiotic metabolism will guide personalized medicine and nutrition, inform toxicology risk assessment, and improve drug discovery and development.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 28642381 · DOI · PMC5534341
Cytochrome P450 Enzymes and Drug Metabolism in Humans [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Human cytochrome P450 (CYP) enzymes, as membrane-bound hemoproteins, play important roles in the detoxification of drugs, cellular metabolism, and homeostasis.
- Closing excerpt
- Additionally, genetic and epigenetic factors, as well as several intrinsic and extrinsic factors that contribute to interindividual variation in drug response are also reviewed, to reveal the multifarious and important roles of CYP-mediated metabolism and elimination in drug therapy.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (196 words)
Human cytochrome P450 (CYP) enzymes, as membrane-bound hemoproteins, play important roles in the detoxification of drugs, cellular metabolism, and homeostasis. In humans, almost 80% of oxidative metabolism and approximately 50% of the overall elimination of common clinical drugs can be attributed to one or more of the various CYPs, from the CYP families 1-3. In addition to the basic metabolic effects for elimination, CYPs are also capable of affecting drug responses by influencing drug action, safety, bioavailability, and drug resistance through metabolism, in both metabolic organs and local sites of action. Structures of CYPs have recently provided new insights into both understanding the mechanisms of drug metabolism and exploiting CYPs as drug targets. Genetic polymorphisms and epigenetic changes in CYP genes and environmental factors may be responsible for interethnic and interindividual variations in the therapeutic efficacy of drugs. In this review, we summarize and highlight the structural knowledge about CYPs and the major CYPs in drug metabolism. Additionally, genetic and epigenetic factors, as well as several intrinsic and extrinsic factors that contribute to interindividual variation in drug response are also reviewed, to reveal the multifarious and important roles of CYP-mediated metabolism and elimination in drug therapy.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 34884615 · DOI · PMC8657965
Nutrient environment improves drug metabolic activity in human iPSC-derived hepatocytes and HepG2 [4]
Abstract reading summary — source excerpts
- Opening excerpt
- Induced pluripotent stem cells (iPSCs) have emerged as a transformative tool in regenerative medicine, in liver research.
- Closing excerpt
- Likewise, HLCs hold the widest CYP coverage at the transcript level and were able to cope with a wide variety of chemical insults, making them a promising model for personalized metabolic studies.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (249 words)
Induced pluripotent stem cells (iPSCs) have emerged as a transformative tool in regenerative medicine, in liver research. The perspective of a stable and functional source of hepatocytes has led to developing protocols for human iPSC-derived hepatocytes-like cells (HLCs). Yet, hepatic models remain one of most challenging systems to functionally reproduce with iPSCs, due to its resulting limited metabolic function. Using an adapted nutrient regimen, two human hepatocyte models were characterized: HLCs (derived from iPSCs) and metabolically active HepG2 (mHepG2, derived from the cell line HepG2), for their drug metabolism activity. In these cell systems, the transcriptome, proteome, and metabolome of 11 drug-relevant cytochrome P450 (CYP) isoenzymes were studied. A liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach, using model drugs as isoenzyme reporters, was applied, achieving a comprehensive overview of mHepG2 and HLCs drug metabolism. Drugs used in this study to characterize xenobiotic machinery were: bupropion (25 µM), phenacetin (30 µM), rosiglitazone (10 µM), diclofenac (75 µM), dextromethorphan (15 µM), chlorzoxazone (60 µM), midazolam (15 µM), benzydamine (15 µM), coumarin (250 µM) and 7-ethoxycoumarin (60 µM). Being HepG2 notorious for its limited metabolic capacity, our study raises mHepG2 as a highly performant cell model, with activity on 8 drug-metabolizing CYPs. Modulation by nutrient environment in improving metabolic function of in vitro models is here proven as a key determinant. Likewise, HLCs hold the widest CYP coverage at the transcript level and were able to cope with a wide variety of chemical insults, making them a promising model for personalized metabolic studies.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40794106 · DOI · PMC12477091
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Cytochrome P450 Structure, Function and Clinical Significance: A Review [5]
- Research article The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism [6]
- Research article Therapeutic and toxic blood concentrations of nearly 1,000 drugs and other xenobiotics [7]
- Research article Survey of Human Oxidoreductases and Cytochrome P450 Enzymes Involved in the Metabolism of Xenobiotic and Natural Chemicals [8]
- Research article Inhibition and induction of CYP enzymes in humans: an update [9]
- Research article Liver hypertrophy: a review of adaptive (adverse and non-adverse) changes--conclusions from the 3rd International ESTP Expert Workshop [10]
References
- Davis AP, Grondin CJ, Johnson RJ, Sciaky D, Wiegers J, Wiegers TC, et al.. Comparative Toxicogenomics Database (CTD): update 2021. . 2021. PMID 33068428 · DOI · PMC7779006
- Koppel N, Maini Rekdal V, Balskus EP. Chemical transformation of xenobiotics by the human gut microbiota. . 2017. PMID 28642381 · DOI · PMC5534341
- Zhao M, Ma J, Li M, Zhang Y, Jiang B, Zhao X, et al.. Cytochrome P450 Enzymes and Drug Metabolism in Humans. . 2021. PMID 34884615 · DOI · PMC8657965
- Pozo Garcia V, Çobanoğlu TS, Hammer HS, Carlota R, Holm K, Verfaillie C, et al.. Nutrient environment improves drug metabolic activity in human iPSC-derived hepatocytes and HepG2. . 2025. PMID 40794106 · DOI · PMC12477091
- Manikandan P, Nagini S. Cytochrome P450 Structure, Function and Clinical Significance: A Review. Curr Drug Targets. 2018. PMID 28124606 · DOI
- Spanogiannopoulos P, Bess EN, Carmody RN, Turnbaugh PJ. The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism. Nat Rev Microbiol. 2016. PMID 26972811 · DOI · PMC5243131
- Schulz M, Iwersen-Bergmann S, Andresen H, Schmoldt A. Therapeutic and toxic blood concentrations of nearly 1,000 drugs and other xenobiotics. Crit Care. 2012. PMID 22835221 · DOI · PMC3580721
- Rendic S, Guengerich FP. Survey of Human Oxidoreductases and Cytochrome P450 Enzymes Involved in the Metabolism of Xenobiotic and Natural Chemicals. Chem Res Toxicol. 2015. PMID 25485457 · DOI · PMC4303333
- Hakkola J, Hukkanen J, Turpeinen M, Pelkonen O. Inhibition and induction of CYP enzymes in humans: an update. Arch Toxicol. 2020. PMID 33111191 · DOI · PMC7603454
- Hall AP, Elcombe CR, Foster JR, Harada T, Kaufmann W, Knippel A, et al.. Liver hypertrophy: a review of adaptive (adverse and non-adverse) changes--conclusions from the 3rd International ESTP Expert Workshop. Toxicol Pathol. 2012. PMID 22723046 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.