Ayurgenomics: A Novel Integrative Research Framework of Ayurveda and Genomics towards P5 Medicine

K Sangeetha; Bhavana Prasher

doi:10.4103/jras.jras_109_23

MANN KI BAAT - SPL. ISSUE - SECTION 2: SCIENCE & EVIDENCE

Year : 2023 | Volume : 7 | Issue : 5 | Page : 13-18

Ayurgenomics: A Novel Integrative Research Framework of Ayurveda and Genomics towards P5 Medicine

K Sangeetha, Bhavana Prasher
Centre of Excellence for Applied Development of Ayurveda Prakriti and Genomics, Genomics & Molecular Medicine, CSIR-Institute of Genomics & Integrative Biology, Delhi, India; Academy of Scientific and Innovative Research, Ghaziabad, Uttar Pradesh, India

Date of Submission	18-Apr-2023
Date of Acceptance	18-Apr-2023
Date of Web Publication	28-Apr-2023

Correspondence Address:
Dr. Bhavana Prasher
Centre of Excellence for Applied Development of Ayurveda Prakriti and Genomics, Genomics & Molecular Medicine, CSIR‐Institute of Genomics & Integrative Biology, Delhi
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jras.jras_109_23

How to cite this article:
Sangeetha K, Prasher B. Ayurgenomics: A Novel Integrative Research Framework of Ayurveda and Genomics towards P5 Medicine. J Res Ayurvedic Sci 2023;7, Suppl S1:13-8

How to cite this URL:
Sangeetha K, Prasher B. Ayurgenomics: A Novel Integrative Research Framework of Ayurveda and Genomics towards P5 Medicine. J Res Ayurvedic Sci [serial online] 2023 [cited 2023 Jun 8];7, Suppl S1:13-8. Available from: http://www.jrasccras.com/text.asp?2023/7/5/13/374505

Background

Ayurgenomics, an evidence-based approach to personalized medicine that combines traditional Ayurveda and modern genomics and molecular biological techniques, has gained importance in recent years. Our Hon’ble Prime Minister, Shri Narendra Modi has also highlighted the importance of evidence-based research in Ayurveda and understanding apart from explaining the traditional medicine concepts in modern language in many of his “Mann Ki Baat” addresses to the nation. The rising incidence of diseases in the current times and the inter-individual variability in presentation and progression of disease, including drug response, has posed a challenge to the medical field. Importance of preventive and personalized medicine has been greatly realized. Ayurveda’s basic tenet of predictive, preventive, promotive, participatory and personalised approach (P5) towards health and disease could provide methods for addressing these issues. Ayurgenomics an integrative approach of Ayurveda with modern genomics and biology could provide potential solutions through the development of novel predictive biomarkers as well as therapeutics for unmet medical needs.

Prakriti, an individual’s body constitution that defines basal health status and to a large extent determines susceptibility to diseases and response to drugs diet and environment, has been explored in depth through multi-omic analysis by CSIR-IGIB and other groups since 2002. This has led to the modern scientific understanding of fundamental principles and practices of Ayurveda, the findings of which are published in the international peer-reviewed journals such as Proceedings of the National Academy of Sciences (PNAS USA) and the Nature group of journals.

Since the development of the Ministry of Ayush in 2014, many such basic science related initiatives have been commenced. Ayurgenomics at IGIB has also received further support in the form of a Centre of Excellence. This has enabled continued integration into various research and education initiatives as well as crosstalk between Ayurveda medicine, modern medicine, and modern science and technology experts. Additionally, the Ministry of Ayush has also integrated Prakriti in Ayush Health and Wellness Centres under the aegis of Ayushman Bharat scheme, with IGIB as the training partner. Overall, Ayurgenomics presents a promising approach to personalized medicine and preventive health measures, with significant potential for future research and development.

Introduction

Ayurveda, India’s traditional system of medicine, has gained global attention in recent pandemic times for its potential in enhancing immunity and preventing diseases. In many of his Mann ki Baat addresses, Prime Minister Modi has emphasized the importance of Ayurveda and the need for evidence-based research in the field. He has pointed out that despite the growing global interest in India’s Ayurveda and Yoga practices, we have not fully acknowledged our own strengths and traditions. PM Modi has also stressed the need for adopting preventive methods and lifestyle modifications to boost immunity, especially in light of the ongoing pandemic. Moreover, he has highlighted the unmet medical conditions still prevalent in the nation that traditional medicine can address.

His words “Just as the world has happily accepted Yoga, the world will surely also accept our age-old Ayurvedic principles. Of course, the youth will have to resolve to do this and explain these principles to the world in a scientific language, so that they understand it.” encourages the younger generation to embrace the challenge of conducting research in Ayurveda and communicating the findings and interpretations using a universal scientific language. With these thrust areas in mind, this article delves into the emerging field of Ayurgenomics and its potential to revolutionize the practice of Ayurveda.

Importance of the concept of Prakriti and the need for research

Prakriti is a fundamental concept in Ayurveda, representing an individual’s unique physical, physiological, and mental constitution, determined by the relative proportion and interaction of the three Dosha - Vata, Pitta, and Kapha. It remains stable throughout life and governs baseline physiological functions at different levels. Recent research suggests Prakriti can be a potential tool for disease prevention, prediction, and personalized medicine administration. Researchers have identified several biomarkers associated with specific Dosha imbalances, such as cytokine profiles, gene expression patterns, and metabolite levels. These biomarkers can help predict the onset of certain diseases and monitor the progress of treatment. Further research is needed to fully understand the relationship between Prakriti and health, including investigating the correlation between Prakriti and Dosha imbalances that lead to disease, and the impact of environmental and lifestyle factors on Prakriti.

Ayurgenomics: A novel integrative framework

Ayurgenomics seeks to integrate the traditional knowledge of Ayurveda with modern advances in genomics, in order to develop personalized medicine that can improve health outcomes for individuals. By analyzing an individual’s phenotypes at structural and functional patterns, as well as analysing their genetic makeup, researchers can identify genetic variations that may increase the risk of certain diseases, and Ayurvedic principles can be used to develop targeted treatments that promote balance and reduce the risk of disease.

The origins of Ayurgenomics can be traced back to the era of Genomics in the 1990s, when the Human Genome Project^[1] was launched to map the entire human genome. The project was completed in 2003, and since then, researchers have been exploring the relationship between genes and health. In the early 2000s, researchers began to investigate the role of Ayurveda in personalized medicine, and the field of Ayurgenomics was born. Today, Ayurgenomics is a rapidly growing field with the potential to transform healthcare by providing personalized, holistic treatments that are tailored to individual needs.

Major research findings till date

The concept of Prakriti, has brought to light the intricate interindividual variability that exists even among those who are considered healthy. This realization has prompted scientists to delve deeper into the baseline heterogeneity between individuals of different Prakriti classifications. By investigating these variations, researchers hope to gain a better understanding of health states, the unique biological and physiological characteristics that underlie variability in health and disease susceptibility. Ultimately, this may lead to the development of more personalized and effective treatments that account for these inherent differences.

In the first study conducted at CSIR-IGIB, healthy individuals of Delhi-NCR region, age and gender matched were classified into seven Prakriti types. Three extreme Prakriti types were further analysed in detail for biochemical and genome-wide gene expression variations. Distinct patterns of gene expression and differences in metabolites and hematological profiles were found amongst three extreme Prakriti.^[2] The research identified key genes and pathways that were differentially expressed among Prakriti. EGLN1, a key oxygen sensor gene was amongst several genes that differed significantly between Pitta and Kapha Prakriti individuals dwelling at sea level. It was hypothesized that the genetic variations responsible for the differential expression that correlates with Prakriti phenotypes may serve as potential indicators for comprehending systems level variability in baseline and in adaption to external surroundings. Hence this led the researchers to look into the genetic variations in these genes. It was found that there were variations at single nucleotide polymorphisms (SNP) in EGLN1^[3] gene that correlated with expression levels in Prakriti specific manner and also associated with high altitude and hypoxia responsiveness in global and Indian populations. This led to the discovery of novel predictive markers through the Ayurgenomics approach and the findings was published in the Proceedings of National Academy of Sciences, USA. Further to this researchers also identified SNP in a few other genes including VWF^[4] genes, which is a platelet glycoprotein, known to take part in blood clotting, to be differing between Kapha and Pitta Prakriti. These findings not only provide insights into the genetic basis of Prakriti but also their importance in predicting outcomes in hypoxic environment and explaining the basis for personalized recommendations for health and treatments. Researchers from Pune have also been able to find correlations between Prakriti and human leucocyte antigen (HLA)DRB1 types. If validated, this hypothesis would have implications for pharmacogenomics, genetics, human health, and Ayurveda.^[5]

Another exploratory study from Delhi University tested whether Prakriti-based subgrouping can overcome phenotypic heterogeneity in genetic association studies for RA. Results suggest that different pathways underlie the disease in different subgroups based on Prakriti. Inflammatory genes were observed to be the determinants in Vata, while oxidative stress pathway genes are observed in Pitta and Kapha subgroups.^[6] This validates the concepts of Prakriti and personalized medicine in Ayurveda.

Researchers from Ayurveda biology initiative found 52 SNPs that were significantly different between Prakritis.^[7] PCA of these SNPs classified 262 individuals into their respective groups. They found that PGM1 correlates with the phenotype of Pitta as described in Caraka Samhita. This suggests that the phenotypic classification of India’s traditional medicine has a definitive genetic basis.

In another study, next-generation sequencing based analysis of healthy individuals of extreme Prakriti types from two cohorts (Northern and western Indian)was carried out at IGIB.^[8] The study primarily aimed to identify functional variations associated with Prakriti types by performing exome sequencing on healthy individuals stratified by Prakriti methods. The study revealed differential risk for diseases/traits like metabolic disorders, liver diseases, and body and hematological measurements amongst healthy individuals of extreme Prakriti types. A core set of 115 single nucleotide polymorphisms were found to replicate with exact patterns of allele frequency differences amongst Prakriti groups in both cohorts despite differences in genetic background. From this set, novel leads in IFIT5 and SERPINA10 genes were found that could explain differential immune response, bleeding- thrombosis outcomes in disease trajectories in Prakriti.^[8]

Researchers have also explored the relationship between Prakriti types and the genetic polymorphism of the CYP2C19 gene. The study found that the gene variation was associated with metabolic variability among the groups.^[9] Another study also provides analysis of genetic variability in FDA approved pharmacogenomics genes/SNPs in healthy individuals of extreme Prakriti types in a North Indian Cohort.^[10] These studies highlight the potential of integrating traditional medicine with modern pharmacogenomics for discovery of markers for personalized medicine.

In addition to host genome, the human system is home to diversified microbial components. The establishment and colonization of the human microbiome is an outcome of collective host-microbiome and microbe-microbe interactions, and forms the crucial basis for human health and disorders. Metagenomic studies are thus a thrust area in Genomics. Many phenotypic attributes that differ between Prakriti types influence the gut microbiota in an individual. A study found that Bacteroidetes and Firmicutes were major gut microbial components in varying composition across Prakriti.^[11] Multiple species of the core microbiome showed differential abundance within Prakriti types, with gender-specific signature taxons. Significant overabundance of P. copri, among female Kapha individuals which is known to be associated with RA and insulin resistance phenotypes was another major finding. Despite an overall uniform composition of gut microbial community, healthy individuals belonging to different Prakriti groups have enrichment of specific bacteria that are reported to be associated with different health outcomes.

These studies established the corelation between Ayurveda’s concept of dosha and Prakriti with modern biology and further exploration of molecular mechanism of dosha-specific therapeutic interventions have led to validation of these and provided repurposing opportunities of Aushadha axis of Trisutra Ayurveda as follows.

In the Trisutra paradigm of Ayurveda, the Dosha-aushadha axis assumes a pivotal role in the identification and selection of suitable pharmacological interventions for the treatment of specific pathological conditions. Mechanistic studies undertaken on the Dosha-aushadha axis with diverse herbs to further elucidate their mechanisms of action and therapeutic efficacy in various pathological conditions. Adhatoda Vasica or “Vasa” which is Pitta-Kapha balancing herb, has been described in Ayurveda for treatment of various respiratory disorders including asthma (Tamaka Shwasa), fevers (Jwara) and tuberculosis (Kshaya). Researchers at IGIB investigated the potential therapeutic effects of Adhatoda vasica, on acute and severe asthmatic mice “https://paperpile.com/c/2UfzWK/q25R”^[12] and found that it significantly improved the respiratory function of asthmatic mice by reducing inflammation, airway hyper responsiveness and cellular hypoxic response and in the lung tissue. Study further suggested that Adhatoda vasica may have therapeutic potential for treating acute and severe asthma by modulating cellular hypoxic response and mitochondrial dysfunction. During the course of investigation into the medicinal properties of this herb, coinciding with the onset of the COVID-19 pandemic, the research team was also intrigued by the presence of bioactive compounds within the plant that have the potential to mitigate host response in terms of reversing the inflammation and hypoxia- thrombosis outcomes, both of which have been linked with the manifestation of severe COVID-19 symptoms “https://paperpile.com/c/2UfzWK/tnXP”^[13]. More in-depth studies on this also showed its potential in viral inhibition as well. The findings suggest that the plant may have a role in mitigating the adverse effects associated with COVID-19, such as Acute respiratory distress syndrome (ARDS) and cytokine storm syndrome. Overall, the study provides promising evidence for repurposing of Adhatoda Vasica as a potential therapeutic intervention for COVID-19.

Along the similar lines, another herb, Cissampelos pareira L. (CIPA) that has been documented to be useful for diverse conditions such as female hormone disorders (Stanya Shodhana) and fever (Jwaraghna), was found to have molecular links to viral inhibitors identified through transcriptomic studies of cell lines treated with CIPA extract “https://paperpile.com/c/2UfzWK/zXjF”^[14]. Further analysis showed that extract from this plant can modulate the expression of estrogen receptor and also exhibit anti-viral activity. This also highlights the potential of uncovering novel biological links between diseases and treatments through systematic exploration of Aushadha axis. Subsequent studies also suggest that CIPA may have potential therapeutic applications in the treatment of SARS CoV2.^[15]

Another study on Tinospora cordifolia extract conducted on T-cell assays followed by transcriptomic analysis showed that it downregulated the expression of genes associated with Th17 cells proliferation and differentiation leading to reduced production of inflammatory cytokines “https://paperpile.com/c/2UfzWK/1w4g”^[16]. These findings explain its mechanism and potential for use as a therapeutic agent in autoimmune and inflammatory diseases.

Hence, deconvolution of Ayurvedic concepts and mechanism of action of medicines into modern language has the potential to enable the repurposing of drugs for various pathologies with shared molecular pathophenotypes. This approach could lead to not only the development of more effective treatments for a wide range of diseases, but also the discovery of new therapeutic targets.

An individual’s tendency to respond to external environment is hardwired in their Prakriti. Environmental stressors can impact an individual’s health in a Prakriti specific manner. Response to stressors can vary among individuals with different Prakriti types. Studying the effects of stressors on individuals with different Prakriti is essential for personalised medicine. A recent Ayurgenomics study reports inter-individual differences in heart rate variability during head-up tilt among healthy individuals of extreme Prakriti types.^[17] These findings suggest that an individual’s Prakriti type may influence their response to orthostatic stress and could be considered when assessing cardiovascular health.

Conducting experiments on human subjects for stressors like Heat shock or U.V is challenging. Researchers often turn to in-vitro cell line models to study the impact of stressors. These models allow scientists to study cellular responses to stress in a controlled environment and measure their effect at phenotype, cellular process, as well as at molecular level including alterations in gene expression, protein synthesis, and signalling pathways. At CSIR-IGIB a unique resource in terms of Prakriti specific lymphoblastoid cell lines (LCLs) has been created to understand the baseline variability that could exist among different Prakriti types. Lymphoblastoid cell lines were derived from peripheral blood samples and the proliferation rates and response to UV exposure were measured and compared between the Prakriti types.^[18] The results showed that the baseline proliferation rates and response to UV exposure differed significantly between the constitution types, with Vata Prakriti had higher rates of cell proliferation at baseline compared to kapha. In response to UV, Vata shows higher cell death but recovers its numbers due to an inherent higher rates of proliferation. This study highlighted the importance of understanding baseline differences underlying Prakriti for better interpretation of the outcomes of stress response which could have implications for disease risk, prevention and treatment outcomes.

The future implications

The emergence of studies in the area of Ayurgenomics and Prakriti has significant implications for public health, preventive and personalized medicine. The combination of ancient Ayurvedic knowledge and modern genomic technology can lead to a personalized approach to healthcare.^[19] The findings of such studies can help in identifying an individual’s unique genetic makeup, predispositions, and susceptibilities to various diseases. This, in turn, can help healthcare professionals tailor personalized treatment plans, optimize drug therapies, and even prevent diseases before they occur.

Moreover, by using Ayurvedic knowledge to subgroup individuals based on their Prakriti, researchers can overcome the limitation of phenotypic heterogeneity commonly encountered in case-control based genetic association studies. Using the wealth of knowledge elaborated in the ancient texts and testing it in the modern scientific & research framework will also enable crosstalk between sciences. The results coming out of such integrative studies will benefit and add on to the existing knowledge as well as enabling the repurposing of the findings in other related or novel thrust areas.

In the current scenario, Ministry of Ayush has undertaken a very large-scale initiative of implementation of personalised and Holistic Health approach at public health settings, under AYUSHMAN Bharat yojana. Prakriti based preventive health and wellness programmes has been introduced for personalised health & lifestyle recommendations at AYUSH Health and wellness centres across the country. CoE on Ayurgenomics CSIR-IGIB is privileged to be training partner. Such initiatives could provide impetus to other countries in adopting their respective, well accepted TM concepts and practices for primary prevention and wellness as new pathways to accelerate SDG3 by 2030.

Hence, in the future, the integration of Ayurgenomics and Prakriti in healthcare can lead to a more efficient, effective, and patient-centered healthcare system. By utilizing this knowledge, healthcare providers can reduce the burden of chronic diseases and provide cost-effective treatment options, reduce risk of adverse drug reactions, and improve health outcomes. Overall, the impact of Ayurgenomics and Prakriti on public health and personalized medicine is promising and offers a new direction for healthcare.

Acknowledgments

Authors acknowledge M/o Ayush and CSIR for funding to conduct Ayurgenomics studies and IGIB for opportunity, ecosystem, infrastructure and administrative support. The authors would also like to acknowledge the Trisutra Ayurgenomics collaborative network of scientists and students including study participants.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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