he human body that we see is composed of trillions of cells. It is fascinating to note that not all cells in our body are of human origin but they include tiny microorganisms as well. We have a good number of these little creatures in our gastrointestinal tract (gut) that together are known as the gut microbiota. Besides genetic and environmental factors, this consortium has a crucial role in maintaining human health and in governing the direction of progress and sometimes the treatment of different diseases. For this reason, the gut microbiota is rightly called a ‘metabolic organ’. Advancements in pharmacology have revealed that the interaction between gut microbiota and drugs is a two-way situation, i.e. drugs affect microbiota and vice versa.
While these are microscopic organisms, their effect on the body is anything but minuscule. Yes, they can change the way certain medicines work in the body. With advancement in genomics, microbiology and pharmacology, a new term “pharmacomicrobiomics” has been coined that is defined as the effect of the microbiota on drug disposition, action and toxicity. Variation in microbiota (presence or absence) can control the availability of the active component of the drug (bioavailability) and unwanted and harmful effects of the drug (toxicity and adverse drug reactions) in the body.
Effect of microbiota on drugs
Whenever we pop a medicine, it exerts its effect on the target organ. While doing so it comes in contact with thousands of microorganisms. Like our body synthesizes enzymes to catalyze all sorts of reactions taking place in our body, so do these tiny beings. As a result, the medicines we take are activated or inactivated due to interactions with the body’s enzymes and the enzymes produced by the gut bacteria. So far, more than 180 drugs have been recognized as substrates for gut bacteria. This means that gut microbiota has the potential to decrease or increase the bioavailability or the intended activity of these drugs.
Let us understand this by the simplest of examples. Digoxin is used for treating chronic heart failure. However, in 10 per cent of patients, it is found that the medicine does not show the intended result. Research showed that the key player behind this ineffectiveness of the drug is a bacteria called Eggerthella lenta that is found in the gut. This bacteria could modify the structure of digoxin molecules, thus making the medicine less effective than is intended. Further, taking digoxin along with an antibiotic that would remove this bacteria enhanced the efficacy of the drug as it should have been. This is one of the countless examples demonstrating the effect of gut microbiota on the treatment, explaining that ‘one size fits all’ can not be applied in therapeutics.
Effect of drugs on microbiota
Most of us have heard of the drug metformin. It is one of the most widely recommended drugs for managing blood sugar levels in type-2 diabetes. Research has identified that one of the key reasons metformin is successful in controlling blood sugar is that its mode of action is microbially mediated. It has been found that metformin has a positive effect on the growth of a gut bacteria called Akkermansia muciniphila. These bacteria help to strengthen the lining of our intestines. It’s like adding a protective layer to the walls of our gut. This is essential because a strong and healthy gut lining can prevent harmful substances from leaking into our body and causing inflammation, which leads to the development of diabetes and its complications. Moreover, this microorganism has also been found to improve how our body utilises glucose. It helps the body become more sensitive to insulin. This in turn can better control the amount of sugar in the blood, keeping it within a healthy range.
Gut knowledge is paramount to personalized medicine
Personalized or precision medicine recognizes the importance of differences in the makeup of populations for different treatment outcomes. While this approach has been gaining popularity these days, it is important to understand that knowledge of gut microbiota should be an indispensable component of personalised medicine. Normalizing utilizing a gut microbiome test when conducting clinical trials is one way this can be done.
The relationship between gut microbiota and drugs is an emerging field to improve the efficiency of personalized medicine. Microbes in our gut affect the working of drugs and the same is true the other way round. Understanding the interaction between drugs and gut flora may offer significant guidance for the advancement of precision medicine. Knowing the unique gut microbiota of a patient for personalised medicine is thus the need of the hour.
The author is Co-founder & Director, Leucine Rich Bio Pvt. Ltd. Views expressed in the above piece are personal and solely that of the author. They do not necessarily reflect Firstpost’s views.