Clinical Cosmos

Pharmacomicrobiomics: The Impact of the Microbiome on Drug Therapy Efficiency

The variability in individuals’ response to medications is a serious issue impacting patient health and generating substantial burdens in both clinical and financial realms. This diversity in response to a drug is caused by several factors, such as the simultaneous use of multiple medications, the patient’s health condition, concurrent intake of food and medications, consumption of substances like alcohol or herbs, and the unique genetics of each individual, the latter recently termed pharmacogenetics (1).

In addition to the previously mentioned factors, it has recently been proposed that the microorganisms comprising the microbiome could also modify drug responses. As a result, the concept of pharmacomicrobiomics has emerged to describe the microbiome’s effects on drug absorption, activity, and toxicity. Within pharmacomicrobiomics, terms such as toxicomicrobiomics and pharmacoecology have been introduced. The former refers to the study of how microbiome variations affect

the metabolism and modify the toxicity of xenobiotics, including drugs. Meanwhile, the latter term is used to conceptualize changes in microbial taxa or specific functions of the microbiome resulting from the administration of a drug with either microbicidal or promicrobial activity (2).

Although pharmacomicrobiomics focuses on the microbiome, the set of organisms that share a symbiotic relationship with humans, by studying their genome and their interaction with the host genome, most studies in this field have focused solely on the gut microbiota (2,3). This trend is not surprising, considering that about 90% of medicines consumed worldwide are administered orally and that the gut microbiota exhibits the greatest diversity among microbiota in the human body (4,5).

Currently, it’s been proposed that the intestinal microbiota significantly influences the processes of drug absorption, distribution, metabolism, excretion, and potential toxic effects, primarily through two fundamental mechanisms: drug accumulation and metabolism by the microbiota. Accumulation involves bacteria’s capability to store drugs within their cells without altering their chemical structure, resulting in two outcomes: a reduction in drug availability and changes in the microbial community’s composition. Regarding drug metabolism, intestinal microorganisms have been observed to modify drugs through processes such as oxidation, reduction, acetylation, deamination, hydrolysis, among others (6,7).

Despite a remarkable increase in the number of publications on pharmacomicrobiomics in recent years, understanding of the relationship between the microbiome and the host remains limited. A suggestive 2018 study compares microbiome research to the growth of a child, indicating that it is transitioning from infancy to learning to walk, but has yet to mature to fully understand its environment (8). Throughout history, humans have maintained an intimate relationship with the microbial world. Many microorganisms operate in symbiosis and are essential for human health and well-being. The study of this relationship between microorganisms and humans has sparked significant interest within the scientific community, showcasing a promising field for exploration.

In conclusion, the variability in drug response poses a complex challenge. Pharmacomicrobiomics stands out as a promising field, especially in exploring the intestinal microbiota and its critical processes of drug accumulation and metabolism. Despite the growing research interest, our understanding of the relationship between the microbiome and the host remains limited. Nevertheless, this field presents vast opportunities for future research and groundbreaking discoveries.

Itzae Adonai Gutierrez Hurtado, PhD

Professor and researcher at the Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara; PhD in Human Genetics

References

[1] S. Rai, G., J. Rozario, C. (2023). Mechanisms of drug interactions II: pharmacokinetics and pharmacodynamics. Anaesthesia & Intensive Care Medicine (4):217–20.

[2] Torres C. N., Martínez, L. E., Torres, C, N., López, Q. A., Moreno, O. J., González, M. A.,etal. (2023). Pharmacomicrobiomics and Drug–Infection Interactions: The Impact of Commensal, Symbiotic and Pathogenic Microorganisms on a Host Response to Drug Therapy. Int J Mol Sci. 24(23):17100.

[3] Perez N., B., Dorsen C., Squires, A. (2020) Dysbiosis of the Gut Microbiome: A Concept Analysis. Journal ofHolistic Nursing 38(2):223–32.

[4] Peretti S, Torracchi S, Russo E, Bonomi F, Fiorentini E, Aoufy K El, et al. (2022). The Yin-Yang Pharmacomicrobiomics on Treatment Response in Inflammatory Arthritides: ANarrative Review. Genes (Basel);14(1):89.

[5] Alqahtani, M. S., Kazi, M., Alsenaidy, M. A., Ahmad, M. Z. (2021). Advances in Oral Drug Delivery. Front Pharmacol; 12.

[6] Jourova, L., Anzenbacher, P., Anzenbacherova, E. (2016). Human gut microbiota plays a role in the metabolism of drugs. Biomedical Papers; 160(3):317–26.

[7] Klünemann, M., Andrejev, S., Blasche, S., Mateus, A., Phapale, P., Devendran, S., et al. (2021) Bioaccumulation of therapeutic drugs by human gut bacteria. Nature; 597(7877):533–8.

[8] Staley, C., Kaiser, T., Khoruts, A. (2018). Clinician Guide to Microbiome Testing. Dig Dis Sci.; 63(12):3167–77.