The Influence of the Microbiome on Drug Action

The advancements in genome sequence technologies and metagenomic analysis have paved the way for scientists to explore the human microbiome. The human microbiome can be described as the genomic sequence of all microbes residing inside the human body.

Human Microbiome

Human Microbiome. Image Credit: Design_Cells/Shutterstock.com

Scientists have approximately estimated around 100 trillion microbes in humans and the bulk of these live in the gut. Microbiome research has enabled scientists to comprehend the microbiome-host interaction mechanism in normal and diseased conditions. It also helps understand the influence of the microbiome in drug action.

In 2018, around 1000 commonly available drugs for various ailments were tested against 40 strains of human gut bacteria. Researchers reported that approximately one-quarter of the studied drugs revealed antibiotic effect although these were not sold as antibiotics.

A similar study, conducted in 2019, revealed that among the 271 drugs that were exposed to the gut microbes, 176 underwent rapid metabolization such that the level of the drug decreased by more than 20 percent. Bacteria influences different drugs differently. This article discusses the effect of the microbiome on different types of drugs.

Effect of Microbiome on Psychotropic Drugs

A study was conducted to explore the effect of the microbiome on mental health, and its influence on psychotropic drugs. Researchers have found that a small group of gut microbes is associated with mental health conditions (e.g., schizophrenia).

Scientists at APC Microbiome Ireland have successfully transplanted a mood disorder in rats. Such a mood transplant involved the removal of gut microbes with antibiotic treatment and subsequent introduction of gut bacteria from patients suffering from depression. The change in behavior of the treated rats indicates that the microbiome can affect mental health.

Scientists have also reported that some bacteria (e.g., bifidobacteria) can synthesize neurotransmitters, such as dopamine and acetylcholine. They can also produce chemical precursors like tryptophan, which is used to develop serotonin, a mood-regulating chemical. This finding indicates that physicians should consider the gut microbiome before prescribing psychotropic drugs.

Effect of Microbiome on Drugs for Nervous System Disorders

Enterococcus faecalis and Eggerthela lenta are two common gut bacteria that can metabolize the drug l-DOPA. These drugs are generally used to treat Parkinson’s disease. It is known that drugs often undergo degradation owing to the enzymes produced by the host.

Therefore, physicians typically prescribe a second drug alongside l-DOPA to partially counteract the breakdown.

Effect of Microbiome on Cholesterol-lowering Drugs

Sony Tuteja, a pharmacogeneticist at the University of Pennsylvania, studied how gut bacteria influence the action of cholesterol-lowering drugs. Her research involved increasing the growth of gut bacteria that produce bile salt hydrolase enzyme. The main function of this enzyme is to breakdown the bile acids used to digest fatty foods. The hepatocyte cells of the liver produce bile salts from cholesterol.

Therefore, when bile acids are broken down, the hepatocyte cells utilize more cholesterol to replace it. Hence, the level of cholesterol decreases in the blood. However, certain bacterial strains are unable to produce a substantial amount of hydrolase. Owing to this reason, statins are less effective in some people.

The Effect of Microbiome on Cancer Drugs

Scientists have reported that gut microbes can modulate the immune system. This observation explains the influence of the microbiome on cancer immunotherapy. Thomas Gajewski, an immunotherapy researcher at the University of Chicago, and colleagues have researched to understand the effect of the gut microbiome on cancer drugs. They collected fecal samples from patients with melanoma.

The sample was collected before administration of anti-PD-1 checkpoint inhibitor. The function of this drug is to block the T cell receptor (PD-1) which is used by cancer cells to evade host immunity.

Gajewski’s team reported Bifidobacterium longum, Collinsella aerofaciens, and Enterococcus faecium are abundantly present in the gut of the patients for whom immunotherapy was successful. Other scientists have also reported similar results where the microbiome showed a positive effect on the cancer drugs, but the bacterial composition in the gut was different.

Bacteria belonging to the Ruminococcaceae family, Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, and Holdemania filiformis have also shown a positive response to various cancer drugs such as anti-PD-1 CPI and a different type of CPI for patients with metastatic melanoma.

Another gut bacterium, namely, Akkermansia muciniphila has also been identified to have a positive response on patients who are suffering from lung, renal, or urothelial carcinoma and have undergone anti-PD-1 immunotherapy.

Challenges in Studying the Complex Interaction Between Drugs and the Microbiome

One of the main challenges in the study of the gut microbiome is the presence of innumerous species of bacteria in the human gut that have 150 times more genes than the human genome. Additionally, the microbiome profile of every individual varies. This implies that the study of every gene and correlating it with metabolism is an enormous task.

Another limitation is the fact that microbiomes also vary from region to region. Such variation could have a different consequence on drug treatment. For instance, positive drug treatment in America might not show a similar result in other parts of the world. Further, the microbiome interacts with drugs utilizing different mechanisms. To tackle this problem, scientists have studied the effect of individual drugs on gut bacteria by administering them one by one and categorizing the bacteria with regards to their response to the drugs.

Conclusion

Scientists believe that understanding the interaction between microbes and drugs could lead to the development of many novel therapies. It could also promote a change in the process of application of drugs and, thereby, enhance their efficacy.

Modifications in the food habits and antibiotics could bring about a change in an individual's gut microbiome which would, in turn, alter the efficacy of various drugs.

Sources:

  • Savage, N. (2020). The complex relationship between drugs and the microbiome. Nature.  577, S10-S11. doi: https://doi.org/10.1038/d41586-020-00196-0
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  • Matson, V. et al., (2018). The commensal microbiome is associated with anti–PD-1 efficacy in metastatic melanoma patients. Science. 359, pp.104-8
  • Gopalakrishnan, V. et al. (2018). Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients. Science. 359, pp.97-103.
  • Kessel, van S.P. et al. (2019). Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson’s disease.  Nat Commun. 10, pp. 310.
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Further Reading

Last Updated: Mar 17, 2021

Dr. Priyom Bose

Written by

Dr. Priyom Bose

Priyom holds a Ph.D. in Plant Biology and Biotechnology from the University of Madras, India. She is an active researcher and an experienced science writer. Priyom has also co-authored several original research articles that have been published in reputed peer-reviewed journals. She is also an avid reader and an amateur photographer.

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