Published On: 14th January, 2024
ABSTRACT
The human microbiome, comprising trillions of microorganisms inhabiting the human body, plays a pivotal role in maintaining health and impacting the development of diseases. This article explores the complicated relationship between the human microbiome and the framework of personalized medicine. The human microbiome, with its unique composition and functionality, is a potential resource for personalized medical interventions. By understanding how individual microbiomes influence drug metabolism, diagnostic approaches, and disease susceptibility, we can pave the way for a new era in healthcare. This article delves into the definition and composition of the human microbiome, its role in health and disease, the evolution of personalized medicine, and the promising union of these fields. Challenges and ethical considerations are also addressed, highlighting the need for careful navigation through these significant changes. As we unravel the mysteries of the microbiome, personalized medicine stands to benefit immensely from tailor-made treatments to the unique microbial fingerprint of each individual.
Keywords: human microbiome, personalized medicine, microbiota, biomarker
INTRODUCTION
The microbiome is a collection of microorganisms such as bacteria, viruses, and fungi that exist and thrive in specific environments. The human body also contains these microorganisms that live on or inside the body like on the skin or in the digestive system (Microbiome, n.d.).
The microbiome population or microbiota serves to help human health in various ways.
They benefit several vital functions in the human body like regulation of the immune system, digestion of food, production of vitamins such as B12 and K, metabolization of xenobiotic materials, etc. There are a lot of factors that affect the human microbiome, such as diet, medicines including antibiotics, relationships with the environment, pregnancy, and age. The lack of these microorganisms may contribute to many diseases like type I diabetes (autoimmune disease), rheumatism, muscular dystrophy, problems in blood coagulation due to lack of vitamin K, and disturbances in the transfer of nerve cells due to lack of vitamin B12. The absence of microbiota may also lead to conditions such as cancer, memory disorders, depression, stress, autism, and Alzheimer’s disease (Altveş et al., 2020).
Personalized medicine is an emerging field in science that makes use of a person’s genetic makeup to drive the decision-making process in the prevention, diagnosis, and treatment of diseases (Personalized Medicine, n.d.). We can say that it is a better approach to healthcare as opposed to the ‘one size fits all’ system. The treatments can be tailored as per the individual’s disease based on the person’s genetic profile.
Personalized medicine has the potential to offer improved medication selection and targeted therapy, reduce adverse effects, increase patient compliance, shift the goal of medicine from reaction to prevention, improve cost-effectiveness, and increase patient confidence post-marketing by approving novel therapeutic strategies, and alter the perception of medicine in the healthcare system (Mathur & Sutton, 2017).
UNDERSTANDING THE HUMAN MICROBIOME DEFINITION AND COMPOSITION
The term “human microbiome” refers to the genetic material of microorganisms (microbiota) that live at a specific location within the human body. It comprises bacteria, archaea, viruses, and eukaryotes which reside within and outside our bodies. These microorganisms colonize various anatomical body sites such as the skin, the mucosa, the gastrointestinal tract, the respiratory tract, the urogenital tract, and the mammary gland, with the majority of the microbiota living in the gut, predominantly in the large intestine (Ogunrinola et al., 2020).
The human body is mostly composed of microbes. There are roughly over 100 trillion of them, outnumbering the human cells by about ten to one. The number of genes in all the microbes in one person’s microbiome is approximately 200 times the number of genes in the human genome. The total microbiome genomic content in a person may weigh as much as five pounds (Hair & Sharpe, 2014).
There is a varied range of microorganisms present in each part of the human body. This is known as microbial diversity (see Appendix A for a list of the various organisms that reside in the gut, mouth, penis, vagina, uterus, skin, eyes, and lungs).
The human microbiota performs essential functions that define and contribute to the physiology of the host, sharing a unique biological relationship termed symbiosis (Eloe-Fadrosh & Rasko, 2013). This symbiotic relationship between humans and their microbiota is extremely important in maintaining homeostasis in the human body. These symbiotic microbes provide several health benefits to the human body such as host immunity, preventing the colonization and survival of invading pathogens, etc. This relationship is mutually beneficial. One such example is the gut environment and its symbionts. The human gut supplies nourishment to the flora that live there. These microorganisms help with food digestion and absorption, manufacture vitamins like biotin and vitamin K, control immune system activity, and prevent the growth of harmful microbes (Curtis & Sperandio, 2011).
The human microbiome consists of microbes that are both helpful and potentially harmful. The majority are symbiotic—beneficial to both the human body and the microbiota—while a smaller percentage are pathogenic—they encourage disease. But in a healthy body, both pathogenic and symbiotic microbiota coexist without any problems unless a disturbance is caused in that equilibrium due to infections, certain diets, overuse, or prolonged use of antibiotics. In such cases, dysbiosis occurs (opposite of symbiosis), and the normal interactions between the human body and its microbes cease to exist. Therefore, the human body becomes more susceptible to disease (The Microbiome, 2022). Hence, it is important to maintain a balanced environment for a symbiotic relationship between the human body and its microbiota.
Role in Health
The human microbiome plays a significant role in the maintenance and development of the human body. These organisms are responsible for various functions, such as host nutrition, maintenance of homeostasis, colonization resistance, and development of the immune system (Ogunrinola et al., 2020). Two of the important functions, host nutrition, and immunity, are discussed below:
One of the most significant tasks the microbes do for the human body is aid in digestion.
The gut microbiota helps in the metabolism of nutrients and other food components. They produce enzymes to perform functions like the breakdown of polysaccharides, and polyphenols and the synthesis of vitamins. These enzymes are not encoded by the human genome. A major catalytic function of the microbiota is carbohydrate metabolism and transport. They are also involved in the metabolism of other dietary macromolecules, such as proteins (Rowland et al., 2017).
Because of their ability to interact with each other and with human cells, the microbiota releases several cellular substances that majorly influence human nutrition and metabolism (Ramakrishna, 2013).
The host immune system’s induction, training, and operation are significantly influenced by the microbiota. In turn, the immune system strives to maintain a symbiotic relationship with these highly diverse and evolving microbes. The immune system – microbiota induce protective responses to pathogens, maintain regulatory pathways, and provide the ability to tolerate harmless antigens (Belkaid & Hand, 2014). Immune system health primarily depends on the gut microbiota (also known as ‘gut flora’). Optimal microbiota composition helps boost immune defenses in a human host, by acting as a shield against dangerous microbes that could invade the digestive tract, and by also participating in the production of molecules that regulate the immune response (Bioscience, 2020).
So far, we know that optimal microbiota composition contributes to a person’s good health. However, the concept of a healthy microbiome cannot be established without more research. This is majorly due to the sheer volume of microbes present in the human body and the genetic material they contain. Another obstacle is the amount of variability in the composition of the microbiome between individuals is huge and is not completely understood by scientists and researchers. This variability may be due to reasons like hereditary, environmental, and lifestyle factors (Morton, 2022). While there is more research required to understand the concept of a healthy microbiome, a few lifestyle changes have been proven to help in promoting microbiota health. A wholesome diet, and the use of probiotics, prebiotics, and symbiotics are a few such examples that have been known to enrich the gut flora with “good” bacteria (Bioscience, 2020).
Dysbiosis and Disease
Dysbiosis is defined as the imbalance of microbial species and a reduction in microbial diversity in the microbiomes present in certain parts of the human body. This results in the reduction of “good” bacteria, whereas there may be an increase in harmful bacteria. Dysbiosis is mainly caused due to impaired gut barrier function and immune-mediated inflammation, which is a result of excessive immune response. Hence, we can say that there is a potential association between intestinal dysbiosis and certain conditions, including inflammatory bowel disease (IBD), diabetes mellitus, and colorectal cancer.
(Armata, n.d.).
Personalized Medicine
Definition and Evolution
Personalized medicine may be defined as the practice of medicine that uses an individual’s genetic profile to guide decisions made regarding the prevention, diagnosis, and treatment of disease (Personalized Medicine, n.d.).
The phrase ‘personalized medicine’ was first introduced to the general public during the late 1990s. However, the concept of individualized pharmacotherapy was on the agenda of healthcare providers years or decades before that. The principles of individualized pharmacotherapy were essentially based on the premise that individual patients should receive medications appropriate to their clinical needs to optimize the benefits and minimize harm. The same principles are applied in personalized medicine today but with one major difference, which is the increase in molecular understanding of the pathophysiology and the mechanisms of action of drugs, which is essential to the implementation of both individualized pharmacotherapy and personalized medicine (Jørgensen, 2019).
Various technological advancements have facilitated the rise of personalized medicine. One such example is the development of next-generation sequencing (NGS) technology, which enables rapid and cost-effective analysis of an individual’s entire genome. NGS has revolutionized genetic testing by allowing healthcare professionals to identify genetic variations more efficiently. This has not only helped scientists and researchers better understand the genetic basis of diseases but has also paved the way for healthcare professionals to look into personalized treatment approaches. There are also other technological innovations, such as artificial intelligence and machine learning algorithms, that have contributed to the growth of personalized medicine. These tools are capable of analyzing large datasets and identifying patterns that may not be apparent to the human eye, enabling more accurate diagnoses and treatment recommendations (Brains, 2023).
The Promise of Personalized Medicine
Personalized medicine is about tailoring a medical treatment to an individual’s genetic makeup. The treatment will be as individualized as the disease. Personalized medicine increases the ability to predict which medical treatments will be safe and effective for an individual, and which ones will not be, based on the patient’s unique genetic profile, as opposed to the traditional ‘one-size-fits-all’ approach. It potentially reduces the expense of time and money and increases the quality of life. Personalized medicine mostly focuses on taking preventative measures, aiding healthcare professionals to make proactive decisions rather than reactive (Mathur & Sutton, 2017).
One of the successful applications of personalized medicine is the discovery of the anticancer drug ‘imatinib’, which is tailored to patients with chronic myelogenous leukemia who carry an enzyme called BCR-ABL tyrosine kinase, a protein produced in individuals with a cytogenetic abnormality known as the Philadelphia chromosome. Imatinib blocks the proliferation of these cancer cells that possess the mutated kinase, effectively reversing the cancerous effects caused due to this specific abnormality.
Another successful application is the use of genotyping to identify variations in enzymes that alter a patient’s sensitivity to the commonly prescribed anticoagulant drug ‘warfarin’.
Information about variations in such enzymes can be used to help guide decisions about the amount of drug that a patient needs to receive to achieve the desired effect (Rogers, 2023).
The focus of personalized medicine has mostly been on cancer treatment. The table below outlines other successful examples of treatment-biomarker combinations in different types of cancers:
|
Biomarker |
Drug name |
Cancer |
|
HER-2/neu receptor |
Herceptin (trastuzumab) |
Breast cancer |
|
BCR-ABL |
Gleevec (Imatinib mesylate) |
Chronic myeloid leukemia |
|
BRAFV600E |
Zelboraf (Vemurafenib) |
Melanoma |
|
EFGR |
Erbitux |
Colon cancer |
|
ALK |
Xalkori |
Lung cancer |
(Cutter & Liu, 2012).
Challenges and Ethical Considerations
Despite the many advantages of personalized medicine, several challenges have cropped up, including ethical, legal, and social concerns. Legal issues begin with obtaining approval of drugs for routine use from various regulatory agencies. There is also a social issue concerning the broad acceptance of personalized medicines by different healthcare stakeholders, such as physicians, insurance companies, and patients (Goetz & Schork, 2018). There is a host of ethical issues raised by personalized medicine related to data privacy, control of data, allocation of healthcare resources, perceptions of different social groups, discrimination, and more (Chadwick, 2013).
There is a need for important guidelines and regulations in personalized medicine to protect the interests of patients, industries, and scientific research without hindering the advancement of this tremendous field (see Appendix B for a complete overview of the challenges impacting the progress of personalized medicine and the required regulatory guidelines to overcome these issues).
The intersection of Human Microbiome and Personalized Medicine Microbiome’s Influence on Drug Metabolism
The human microbiome plays an important role in drug metabolism and efficacy. The variety of microbial species present in the gut metabolize many drugs leading to altered bioavailability, toxicity, and adverse drug reactions affecting the therapeutic efficacy referred to as microbiome-derived metabolism. The gut microbiota affects drug metabolism either by direct interaction or indirect action by interfering with the host metabolism.
The drugs metabolized by microbes can have a different potency than parent drugs or, in some cases, even a toxic potential, hence causing deviations from the expected therapeutic outcomes of the drug. Integrating experimental, computational, and multi-omic approaches will help researchers better understand the gut microbial composition and recognize gut microbiota-mediated drug metabolism. Evaluation of drug metabolism by gut microbiota in drug discovery and development is better for safe and effective drug therapy. The investigation of the host-microbiota symbiotic relationship will aid in the development of more effective and customized pharmacological therapies with the least amount of toxicological side effects and maximal therapeutic advantages after the involvement of gut microorganisms in drug metabolism is confirmed (Dhurjad et al., 2021).
The effect of individual microbiome variations on the disposition and drug/xenobiotic response is termed as pharmacomicrobiomics. Here are a few examples of the most common drugs that are broken down by the gut microbiota: digoxin, amygdalin, ginsenoside, irinotecan, genistein, lovastatin, glycyrrhizin, prontosil, simvastatin, and baicalein (see Appendix C for an overview of the different types of drugs metabolized by gut microbiota). Research shows that antibiotic drugs have the most effect on gut microbiota when compared to non-antibiotic drugs. They are known to negatively affect the gut microbiota diversity, as well as reduce microbiota enzyme function. Eventually, most drugs and xenobiotics disturb the gut microbiota composition and diversity leading to dysbiosis which can cause the development of several diseases and health concerns. More research is required to understand the interactions between the human microbiome and drug metabolism and to also be used as an effective strategy in drug design and personalized medicine (Dikeocha et al., 2022).
Microbiome as a Diagnostic Tool
The human microbiome consists of more than three million genes as opposed to 23000 human genes. This is one of the main reasons why the human microbiota has huge potential as a diagnostic tool for predicting disease susceptibility and treatment response. Studies have shown that the human microbiome and microbiota metabolites can be used as potential diagnostic biomarkers for multiple diseases, including cancer, as well as inflammatory, neurological, and metabolic diseases (see Appendix D for a series of recent studies completed in this area) (Hajjo et al., 2022).
Future Directions
Present-day high-throughput sequencing methods offer valuable insights into the structure and operations of the gut microbiome. However, to improve the efficiency and quality of microbiome research, emerging technologies, like, engineered organoids derived from human stem cells, high-throughput culturing, and microfluidics assays are required that allow the introduction of novel approaches by integrating multiple branches of biology and engineering.
There is a wealth of untapped information within the human microbiome. With faster and more cost-effective sequencing platforms and data analysis pipelines, the concept of using microbiome content as a biomarker for disease is rapidly becoming a possibility. The emerging technologies in various scientific fields will provide the tools needed to further unlock the potential of the human microbiome as a target for personalized medicine (Arnold et al., 2016).
Conclusion
In conclusion, studying how our body’s microorganisms work with personalized medicine is changing how we think about healthcare. Understanding the workings of the microbiome’s influence on drug metabolism, its potential as a diagnostic tool, and its role in disease susceptibility may create opportunities for targeted and effective interventions. Despite the promises, challenges such as ethical considerations and regulatory frameworks must be addressed to ensure the responsible integration of microbiome data and personalized medicine.
As technology advances and more research is done on the subject, the future holds exciting possibilities for harnessing the power of the microbiome to revolutionize healthcare, ushering in an era where treatments are not only tailored to an individual’s genetic makeup but also to the unique microbial biodiversity within. The symbiotic relationship between the human body and its microbiome may indeed unlock the door to a new era of personalized medicine.
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Appendices
Appendix A
Human microbiota: The microorganisms that make us their home https://www.medicalnewstoday.com/articles/human-microbiota-the-microorganisms-that-make-
Appendix B
The path of personalized medicine: regulatory perspective https://www.researchgate.net/publication/326597288_THE_PATH_OF_PERSONALIZED_ME
Appendix C
Pharmacomicrobiomics: Influence of gut microbiota on drug and xenobiotic metabolism https://faseb.onlinelibrary.wiley.com/doi/full/10.1096/fj.202101986R
Appendix D
Gut Microbiome: A Promising Biomarker for Immunotherapy in Colorectal Cancer https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747470
Potential of the Microbiome as a Biomarker for Early Diagnosis and Prognosis of Breast Cancer https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779729
Oral Microbiome: A New Biomarker Reservoir for Oral and Oropharyngeal Cancers https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695015
Microbiome-Based Biomarkers for IBD https://academic.oup.com/ibdjournal/article/26/10/1463/5822885
Applications of Machine Learning in Human Microbiome Studies: A Review on Feature Selection, Biomarker Identification, Disease Prediction and Treatment https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962872