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What is a microbiome?
The microbiome consists of about 100 trillion microbes (microbiota) and their genomes that inhabit the human body. These include bacteriophages (viruses infecting bacteria), fungi, bacteria, protozoa (single-cell eukaryote), and viruses in the human body.
These populations are very important for maintaining health as well as for metabolizing drugs and foreign substances (xenobiotics). The latter is now important in the development of new drugs.
Gut microbiome helps control intestinal digestion and the immune system. Illustration Credit: nobeastsofierce / Shutterstock
Importance of the microbiota
Many drugs need to be converted into their active forms within the body before being able to produce a clinical response. Activation occurs within tissues such as the liver.
The mechanism and metabolism of approved drugs are thoroughly investigated. However, the metabolism by microbiota is an unexplored but important field of study in pharmacology as well as in toxicology.
The diversity and the number of microbiota as well as their ability to metabolize xenobiotics shows how important they are in terms of metabolizing drugs as well as toxic substances. The microbiota are known for altering the pharmacokinetics of a drug, which include the absorption, distribution, metabolism and elimination to enhance the clinical response.
Oral drugs are always a challenge to develop as they must resist adverse gastrointestinal conditions and be properly absorbed to distribute within the body a produce a clinical response.
Although many drugs are now gastrointestinal resistant, it has been reported that microbiota can interfere with the drugs as soon as in the small intestine. This would lead to a change of the drugs pharmacokinetics very early on and could result in less favoured clinical response.
Gut microbiota have been known to interact with drugs for many years. Their importance in health and drug metabolism are now being investigated. A minimum of 2,000 different species can be found within the gut.
The effects of microbiota on drug metabolism
A study by Kang et al. in 2013 explored the xenobiotic (foreign substance) metabolism of natural and synthetic drugs by intestinal microbiota.
The study concluded that the microbiota metabolized the drug differently than did body organs such as the liver; this difference could lead to either activation or inactivation of the substance.
Hence, it would remain unknown if a clinical response can be achieved if drugs are metabolized by microbiota only. Therefore, these researchers suggested further studies to explore this issue, especially during the development of new drugs as well as in comparison with normal metabolism by the tissues of the body.
Another study by Das et al. in 2016 researched the type of bacteria in the gastrointestinal tract in 397 people of different ages and nationalities. They were able to identify 850 different bacteria that could potentially metabolize one or more xenobiotics, which include drugs. However, they also demonstrated their ability to metabolize environmental substances such as gases from fossil fuels. Again, this study shows the important role of the microbiome for drug metabolism and well as for maintaining health by metabolizing toxic gases and fumes from the environment.
A review by Swanson in 2015 evaluated further important roles of intestinal microbiota for health maintenance. The review pointed out that the gut microbiota is vital for the metabolism of bile acid which helps to maintain the health of the host due to its impact on the absorption of lipids and lipid-soluble vitamins as well as maintaining the intestinal barrier function.
As the liver is the main producer of bile acid, the microbiome synthesizes secondary bile acid. Nonetheless, intestinal microbiota actively determine the bioavailability, efficacy, and side effects of drugs, xenobiotics and dietary substances.
Although the outcomes of the review are in line with previous research, it concluded that additional experimental approaches need to be developed to fully understand the impact of the microbiome upon the patients’ response as well the interaction between the host and the microbiome. This could help researchers to predict responses to drugs individually as well as to develop effective and safer therapies.
In a further study by Zimmermann et al. from 2019, 76 human gut bacteria were used to evaluate their metabolic effects on 271 orally administered drugs using mass spectrometry. Around 75% of those drugs were modified by the intestinal bacteria in some way, proving their significant role in drug metabolism.
The future of microbiota
All studies and recent findings demonstrated the importance of the microbiome. Researchers only recently started to investigate in this field. Every study pointed out the important health impact the microbiota has in terms of drug metabolism as well as the metabolism of harmful environmental gases and fumes.
As the microbiome consists of over 100 trillion microbes, the investigation of this research field will always be ongoing towards new approaches and new discoveries which will be beneficial for the future of drug development.
Further Reading
Doxycycline increases antimicrobial resistance in the gut without disrupting microbiome diversity