Intestinal flora effects drug response

August 12, 2016

Intestinal flora has multiple influences on human health, but researchers have revealed that it is also likely to have an effect on the body's response to drugs. Recent research from Kumamoto University in Japan strongly suggests that changes in the intestinal flora, caused by antibacterial and antibiotic drugs or individual differences between people, may have an effect on a person's response to drugs including side effects. The research focused on the changes in proteins due to the condition of intestinal flora that affect the response to drugs in the liver and kidneys.

Antibacterial and antibiotic drugs are often prescribed for the treatment and prevention of bacterial infections and are often taken with therapeutic drugs to prevent recurrence of infection during treatment. Unfortunately, the drugs affect not only harmful bacteria, but also the naturally occurring bacteria within the intestine. To determine the effects of this influence on drug efficacy, Kumamoto University researchers investigated protein changes in the liver and kidney. Changes in these proteins have a great influence on drug efficacy and side effects since they are responsible for the metabolism and transport of many drugs, and are also affected by changes in the intestinal flora.

The research was conducted using three different groups of mice, an experimental group of germ-free mice which were free of intestinal bacteria since birth, a group of mice that had received antibacterial drugs for 5 consecutive days, and a control group of mice with naturally occurring intestinal flora. Researchers used proteomics, a large-scale analysis of proteins, to clarify changes in the amount of the proteins involved in drug metabolism and transport in the liver and kidney of the two experimental mouse groups.

"The most significant drug-metabolizing enzyme that decreased was cytochrome P450 2b10 (Cyp2b10)," said Professor Ohtsuki, who lead the research project. "Not only was the amount of the enzyme reduced nearly 96%, but the metabolic capacity of the drug in the liver was also reduced by approximately 82%. Cyp3a11, a similar type of enzyme was also reduced by about 88%. The human enzymes corresponding to these 2 enzymes, CYP2B6 and CYP3A4 are reported to be related to the metabolism of more than half of the pharmaceuticals on the market."

Additionally, the breast cancer resistance protein (Bcrp1), a protein that transports many kinds of cancer drugs, was reduced by more than 50% in the livers of both experimental groups. Antibacterial drugs are sometimes prescribed to treat and prevent infection caused by bone marrow suppression, a side effect of cancer drugs.

"The results of this study show that many drugs may be affected by changes in the intestinal flora," said Professor Ohtsuki. "In the future, if it is confirmed that similar mechanisms exist in humans, we expect our research to lead to optimal dosing and a reduction in drug side effects."

This finding was posted on Molecular Pharmaceutics, on July 5th, 2016.
-end-
[Citation]
Effect of Intestinal Flora on Protein Expression of Drug-Metabolizing Enzymes and Transporters in the Liver and Kidney of Germ-Free and Antibiotics-Treated Mice
Takuya Kuno, Mio Hirayama-Kurogi, Shingo Ito, and Sumio Ohtsuki
Molecular Pharmaceutics 2016 13 (8), 2691-2701
DOI: 10.1021/acs.molpharmaceut.6b00259

Kumamoto University

Related Metabolism Articles from Brightsurf:

Early trauma influences metabolism across generations
A study by the Brain Research Institute at UZH reveals that early trauma leads to changes in blood metabolites - similarly in mice and humans.

Cannabinoids decrease the metabolism of glucose in the brain
What happens when THC acts on the glial cells named astrocytes ?

New role of arginine metabolism in plant morphogenesis identified
A research team led by ExCELLS/NIBB found that arginine metabolism has a vital role in regulating gametophore shoot formation in the moss Physcomitrium patens.

Watching changes in plant metabolism -- live
Almost all life on Earth, e.g. our food and health, depend on metabolism in plants.

redHUMAN: Deciphering links between genes and metabolism
Scientists at EPFL have developed a new method that simplifies the processing of genetic-metabolic data by picking up changes in metabolism, a hallmark of numerous diseases like cancer and Alzheimer's.

Lipid metabolism controls brain development
A lipid metabolism enzyme controls brain stem cell activity and lifelong brain development.

Inhibition of sphingolipid metabolism and neurodegenerative diseases
Disrupting the production of a class of lipids known as sphingolipids in neurons improved symptoms of neurodegeneration and increased survival in a mouse model.

Viruses don't have a metabolism; but some have the building blocks for one
'Giant viruses' are many times larger than typical viruses and have more complex genomes.

New metabolism discovered in bacteria
Microbiologists at Goethe University Frankfurt have discovered how the bacterium Acetobacterium woodii uses hydrogen in a kind of cycle to conserve energy.

Protein controls fat metabolism
A protein in the cell envelope influences the rate of fatty acid uptake in cells.

Read More: Metabolism News and Metabolism Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.