Published On: 31st March, 2024
ABSTRACT
As more and more studies emerge in the field of personalized medicine it is important to understand its current frontier, i.e., the human microbiome. The association between the human microbiome and personalized medicine is undeniably one of the most intriguing areas of research. The treatment of many diseases, including cancer, heavily relies upon these studies.
In this article, we try to understand the human microbiome and dig deep into its contribution to personalized medicine and how it is truly revolutionary for the field of human medicine.
KEYWORDS – Human microbiome, Precision medicine, Gut microbiota, personalized drugs, future aspect of personalized medicine.
INTRODUCTION – WHAT IS HUMAN MICROBIOME?
Over the years scientists have given various definitions of the human microbiome. In 2003, when the human genome project was completed many were disappointed to find out that there were only 20,000 coding genes in the human genome, but from a broader view, if all the genomes of the microorganisms residing in the human body are taken into consideration this number increases dramatically. Citing a paper from 2007[1], “If we consider ourselves to be a composite of microbial and human species, our genetic landscape a summation of the genes embedded in our human
genome and microbiome, and our metabolic features a coalescence of human and microbial traits, the self-portrait that emerges is one of a ‘human supraorganism’.”
Many researchers often confuse the human microbiome with the human microbiota, the basic
difference between the two is that microbiota also called microflora are the microbial communities, including bacteria, archaea, fungi, etc. living in the human body while microbiome is the genes
encoded by them. Healthy individuals have a microbiome that is characterized by a great variety of microorganisms, most of which are beneficial. These microbes can endure the alterations that occur during physiological stress, whereas the microbiota that is associated with diseases is less varied, containing a smaller number of beneficial bacteria and often results in diseases around areas of inflammation.
The Diversity in Human Microbiome
The core human microbiome (orange part) is the common shared set of genes for all humans in a particular region or habitat while the surrounding blue part represents the variable genes that vary from individual to individual in that population.
This variation could be due to various reasons like lifestyle, dietary habits, environment of
the workplace, or living conditions. Figure[1] – The concept of a core human microbi
MAIN (body)
ASSOCIATION BETWEEN HUMAN MICROBIOME AND PERSONALIZED MEDICINE
Many recent papers [2][3] portray the human microbiome as the new frontier of personalized medicine for various hard-to-treat diseases like cancer. But before going deeper into that let us have a better understanding of what personalized medicine is and how it operates.
A simple definition of personalized/precision medicine can be stated as an innovative approach that utilizes a patient’s genetic profile to make informed decisions related to the prevention, diagnosis, and treatment of diseases. By analyzing a patient’s genetic makeup, healthcare professionals can select the most appropriate medication or therapy, and administer it with the right dosage and schedule. This personalized approach to healthcare holds great promise for improving mortality rates and reducing the occurrence of adverse reactions to treatments. [4][5]
Figure[6] – The relationship between inflammation, cancer, and microbiome
THE GUT MICROBIOTA
The gut microbiota is the most novel and vast in the human body, it makes up for the maximum percentage of the human microbiome.
The human gut contains 50 different microbial phyla but only 2 of those dominate the gut microbiota: the Bacteroidetes and the Firmicutes.[7] The number of bacterial species present in the human gut varies widely among studies, but it is generally accepted that each individual carries more than 1000 microbial, species-level phylotypes.
The main function of the gut microbiota is to assist the digestive juices in digestion. The gut bacteria can produce a variety of vitamins, synthesize all essential and nonessential amino acids, and carry out biotransformation of bile. In addition, the microbiome provides the vital biochemical pathways for the metabolism of non-digestible carbohydrates, which include large polysaccharides, such as
resistant starches, cellulose, hemicellulose, pectin, and gums; some oligosaccharides that escape digestion; unabsorbed sugars and alcohols from the diet; and host-derived mucins.[8]
According to the same above-mentioned research[8] associations between the gut microbiota and several diseases and syndromes have been found lately by researchers. It discusses the relation of these 2 categories of diseases linked with intestinal microbiota, chronic gastrointestinal diseases like IBS and IBD, and systematic metabolic diseases like type 2 diabetes and obesity.
THE SCREENING AND SEQUENCING OF MICROBIOTA
A range of tactics are used to define the microbiome, with the most basic one being the employment of a marker gene that utilizes variable regions present within the highly conserved 16S rRNA gene.
This approach is valuable in assessing alterations in microbial community structure but is unable to provide resolution at species or strain level and fails to provide sufficient functional insight into the community.
Complimentary approaches[2]
Metagenomics: The study of all genomes in an ecosystem.
Metatranscriptomics: Characterization of gene expression from all microbes in an ecosystem
Metabolomics: Characterization of all small molecule metabolites in an ecosystem
Metaproteomics: Characterization of all proteins in an ecosystem
These methods help understand the therapeutic implications of the microbiome by providing greater insight into the functional potential and expression of microbiome-derived bioactive molecules.
PAST EXAMPLES OF PERSONALIZED MEDICINE[10]
For any drug to function efficiently it should mark up to two main criteria – first, the body must respond to the drug, and second, the drug must be absorbed and transported throughout the body or the target site. These processes are studied under Pharmokinetics[9] which can be defined as the study of drug absorption, distribution, metabolism, and excretion. To produce a successful personalized medication, emphasis on the efficacy of the drug is required, this can be calculated by clinically testing the ‘pharmacodynamic properties’ of the drug.
Warfarin is a medication used in the prophylaxis and treatment of venous thrombosis and
thromboembolic events. It is in the anticoagulant class of drugs. It targets a particular gene, VKORC1, and is metabolized in part by the gene CYP2C9. Naturally occurring genetic variation in both the VKORC1 and CYP2C9 genes leads to variation in the pharmacodynamic and pharmacokinetic properties of Warfarin across individuals, ultimately creating variation in individuals’ responses to warfarin.
Example 2 – PRIMAQUINE[10][13]
Primaquine is in a class of medications called antimalarials. It works by killing the organisms that cause malaria. It is only given to those with a specific genetic makeup. Military doctors observed when this drug was given to soldiers to treat malaria, they became anemic and jaundiced and it ultimately caused AHA. It was later shown that the individuals exhibiting AHA after PQ administration carried variants in the G6PD gene.
Imatinib is in the tyrosine-kinase inhibitors class of drugs. It is a 2-phenylamino-pyrimidine derivative protein that is a medication used to manage and treat chronic myelogenous leukemia, gastrointestinal stromal tumors, and other malignancies.
THE FUTURE OF PERSONALIZED MEDICINE
Personalized medicine is a branch of pharma science that carries considerable potential, it represents a great opportunity to improve the future of medicine and healthcare across the globe.
The International Consortium for Personalised Medicine (ICPerMed) believes that the advancement of the biomedical, social, and economic sciences, together with technological development, is the
driving force for PM.[16]
Figure [16] – Vision of ICPerMed by 2030
With the rapid growth in technology and new AI applications, many unexpected opportunities have originated, the use of AI in the healthcare and medicine industry is very promising and carries encouraging prospects.
Three main principles for the successful adoption of AI in health care include data and security, analytics and insights, and shared expertise.[17]
Figure[17] – Synergy between AI and precision medicine.
CONCLUSION & DISCUSSION
The human microbiome, still not completely understood, is a very intriguing topic and shows promise in research work. Its association with personalized medicine is very close and helpful in the production of drugs for cancer, diabetes, gastric syndromes, etc. We can quote that “Personalized medicine or the method of treating individuals based on their genomic makeup and response to a procedure is a necessity.”
Although the technological knowledge and equipment might not be efficient enough to draw out the full potential in this genre in the current scenario, with tech advancements happening so quickly it might not be far when a 100% use of personalized medicine becomes the thing of the present.
ABBREVIATIONS
IBS – irritable bowel syndrome
IBD – Inflammatory bowel disease
AHA – Acute haemolytic anaemia
ICPerMed – International Consortium for Personalised Medicine
AI – Artificial Intelligence
PM – Personalized Medicine
REFERENCES
- Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon The human microbiome projects. Nature. 2007 Oct 18;1. Priority04-10. doi: 10.1038/nature06244. PMID: 17943116; PMCID: PMC3709439.
- Kashyap PC, Chia N, Nelson H, Segal E, Elinav E. Microbiome at the Frontier of Personalized Mayo Clin Proc. 2017 Dec;91. priority.10.004. PMID: 29202942; PMCID: PMC5730337.
- Poroyko V, Manuel ER, and Ilina E (2022) Editorial: The human microbiome: A new frontier in personalized cancer therapy. Cell. Infect. Microbiol. 12:1028120. doi: 10.3389/fcimb.2022.1028120
- https://www.genome.gov/genetics-glossary/Personalized-Medicine
- https://www.cancer.gov/espanol/publicaciones/diccionarios/diccionario-cancer/def/medicina- personalizada
- Behrouzi A, Nafari AH, Siadat The significance of microbiome in personalized medicine. Clin Transl Med. 2019 May 13;8(1):16. doi: 10.1186/s40169-019-0232-y. PMID: 31081530; PMCID: PMC6512898.
- Schloss PD, Handelsman Status of the microbial census. Microbiol Mol Biol Rev. 2004;68(4):686–691.
- Bull MJ, Plummer Part 1: The Human Gut Microbiome in Health and Disease. Integr-Med (Encinitas). 2014 Dec;13(6):17-22. PMID: 26770121; PMCID: PMC4566439.
- Ratain MJ, Plunkett WK Principles of Pharmacokinetics. In: Kufe DW, Pollock RE, Weichselbaum RR, et al., editors. Holland-Frei Cancer Medicine. 6th edition. Hamilton (ON): BC Decker; 2003.
- Goetz LH, Schork Personalized medicine: motivation, challenges, and progress. Fertil Steril. 2018 Jun;109(6):952-963. doi: 10.1016/j.fertnstert.2018.05.006. PMID: 29935653; PMCID: PMC6366451.
- Lee MT, Klein Pharmacogenetics of warfarin: challenges and opportunities. J Hum Genet. 2013;58(6):334–8. doi: 10.1038/jhg.2013.40.
- Patel S, Singh R, Preuss CV, et Warfarin. [Updated 2023 Mar 24]. In: StatPearls [Internet].
Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from
- Galappaththy GN, Tharyan P, Kirubakaran Primaquine for preventing relapse in people with Plasmodium vivax malaria treated with chloroquine. Cochrane Database Syst Rev. 2013 Oct 26;2013(10):CD004389. doi: 10.1002/14651858.CD004389.pub3. PMID: 24163057; PMCID: PMC6532739.
- Flynn JP, Gerriets Imatinib. [Updated 2023 Jun 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan
- O’Dwyer ME, Druker Status of bcr-abl tyrosine kinase inhibitors in chronic myelogenous leukemia. Curr Opin Oncol. 2000;12(6):594–7
- Vicente, M., Ballensiefen, W. & Jönsson, JI. How personalised medicine will transform healthcare by 2030: the ICPerMed vision. J Transl Med 18, 180 (2020).
- Johnson KB, Wei WQ, Weeraratne D, Frisse ME, Misulis K, Rhee K, Zhao J, Snowdon Precision Medicine, AI, and the Future of Personalized Health Care. Clin Transl Sci. 2021 Jan;14(1):86-93. doi: 10.1111/cts.12884. Epub 2020 Oct 12. PMID: 32961010; PMCID: PMC7877825.