Colonization by non-pathogenic bacteria alters mRNA expression of cytochromes P450 in originally germ-free mice
Abstract
Gut microbiota provides a wide range of beneficial function for the host and has an immense effect on the host's health state. It has also been shown that gut microbiome is often involved in the biotransformation of xenobiotics; however, the molecular mechanisms of the interaction between the gut bacteria and the metabolism of drugs by the host are still unclear. To investigate the effect of microbial colonization on messenger RNA (mRNA) expression of liver cytochromes P450 (CYPs), the main drug-metabolizing enzymes, we used germ-free (GF) mice, lacking the intestinal flora and mice monocolonized by non-pathogenic bacteria Lactobacillus plantarum NIZO2877 or probiotic bacteria Escherichia coli Nissle 1917 compared to specific pathogen-free (SPF) mice. Our results show that the mRNA expression of Cyp1a2 and Cyp2e1 was significantly increased, while the expression of Cyp3a11 mRNA was decreased under GF conditions compared to the SPF mice. The both bacteria L. plantarum NIZO2877 and E. coli Nissle 1917 given to the GF mice decreased the level of Cyp1a2 mRNA and normalized it to the control level. On the other hand, the colonization by these bacteria had no effect on the expression of Cyp3a11 mRNA in the liver of the GF mice (which remained decreased). Surprisingly, monocolonization with chosen bacterial strains has shown a different effect on the expression of Cyp2e1 mRNA in GF mice. Increased level of Cyp2e1 expression observed in the GF mice was found also in mice colonized by L. plantarum NIZO2877; however, the colonization with probiotic E. coli Nissle 1917 caused a decrease in Cyp2e1 expression and partially restored the SPF mice conditions.
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Colonization effects are likely strain specific because monoassociation of germ-free mice with both Lactobacillus plantarum Nizo2877 and Escherichia coli Nissle 1917 decreased the expression of Cyp1a2 mRNA to conventional levels but did not act to restore the decreased expression of Cyp3a11 mRNA.
“Colonization effects are likely strain specific because monoassociation of germ-free mice with both Lactobacillus plantarum Nizo2877 and Escherichia coli Nissle 1917 decreased the expression of Cyp1a2 mRNA to conventional levels but did not act to restore the decreased expression of Cyp3a11 mRNA.”
From Gut reactions: Breaking down xenobiotic–microbiome interactions (2019) · cites this paper as Jourova et al., 2017
Differential effects for these strains were noted with increased expression of hepatic Cyp2e1 following monoassociation with L. plantarum Nizo2877 but decreased expression following colonization of E. coli Nissle 1917.
“Differential effects for these strains were also noted with increased expression of hepatic Cyp2e1 following monoassociation with L. plantarum Nizo2877 but decreased expression following colonization of E. coli Nissle 1917(Jourova et al., 2017).”
From Gut reactions: Breaking down xenobiotic–microbiome interactions (2019) · cites this paper as Jourova et al., 2017
In germ-free mice, Cyp1a2 mRNA is increased.
“| Cyp1a2 (mice) | Increased mRNA | Largest effects seen at 90 days | Selwyn et al., 2015a |”
From Gut reactions: Breaking down xenobiotic–microbiome interactions (2019) · cites this paper as Jourova et al., 2017
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Gut reactions: Breaking down xenobiotic–microbiome interactions
Clarke, G., Sandhu, K. V., Griffin, B. T., Dinan, T. G., Cryan, J. F., & Hyland, N. P. (2019) · Pharmacological Reviews · doi:10.1124/pr.118.015768 · Cited by 319 · see citing works
- Authors
- Jourová, L., Anzenbacher, P., Lišková, B., Matušková, Z., Hermanová, P., Hudcovic, T., Kozáková, H., Hrnčířová, L., & Anzenbacherová, E.
- Affiliations
- Palacký University Olomouc (CZ)
- Institute of Molecular and Translational Medicine (CZ)
- Czech Academy of Sciences (CZ)
- Corresponding author
- Anzenbacherová, E.
- Venue
- Folia Microbiologica
- Published
- 2017-03-23
- Volume
- 62
- Issue
- 6
- Pages
- 463-469
- ISSN
- 0015-5632 (ISSN-L)
- 1874-9356
- OpenAlex
- W2600843347
- Cited by
- 26
- References
- 38
- Citations by year
- 2026: 4 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 4 · 2019: 2 · 2018: 2
- FWCI
- 2.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Folia Microbiologica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Grantová Agentura České Republiky (P303/12/0535, 15-07268S)
- Univerzita Palackého v Olomouci (LF_2016_012)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- gut microbiota, microbial colonization, cytochrome P450, CYP1A2, CYP2E1, CYP3A11, drug metabolism, xenobiotic metabolism, Lactobacillus plantarum, Escherichia coli Nissle 1917, probiotics, germ-free mice, hepatic gene expression
- MeSH terms
- Gastrointestinal Microbiome, Animals, Cytochrome P-450 Enzyme System, Escherichia coli, Female, Germ-Free Life, Lactobacillus, Liver, Male, Mice, Inbred BALB C, RNA, Messenger, Mice
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