Genomic insights into ayurvedic and western approaches to personalized medicine

Ayurveda, an ancient Indian system of medicine documented and practised since 1500 B.C., follows a systems approach that has interesting parallels with contemporary personalized genomic medicine approaches to the understanding and management of health and disease. It is based on the trisutra, which are the three aspects of causes, features and therapeutics that are interconnected through a common organizing principle termed ‘tridosha’. Tridosha comprise three ascertainable physiological entities; vata (kinetic), pitta (metabolic) and kapha (potential) that are pervasive across systems, work in conjunction with each other, respond to the external environment and maintain homeostasis. Each individual is born with a specific proportion of tridosha that are not only genetically determined but also influenced by the environment during foetal development. Jointly they determine a person’s basic constitution, which is termed their ‘prakriti’. Development and progression of different diseases with their subtypes are thought to depend on the origin and mechanism of perturbation of the doshas, and the aim of therapeutic practice is to ensure that the doshas retain their homeostatic state. Similarly, western systems biology epitomized by translational P4 medicine envisages the integration of multiscalar genetic, cellular, physiological and environmental networks to predict phenotypic outcomes of perturbations. In this perspective article, we aim to outline the shape of a unifying scaffold that may allow the two intellectual traditions to enhance one another. Specifically, we illustrate how a unique integrative ‘Ayurgenomics’ approach can be used to integrate the trisutra concept of Ayurveda with genomics. We observe biochemical and molecular correlates of prakriti and show how these differ significantly in processes that are linked to intermediate patho-phenotypes, known to take different course in diseases. We also observe a significant enrichment of the highly connected hub genes which could explain differences in prakriti, focussing on EGLN1, a key oxygen sensor that differs between prakriti types and is linked to high altitude adaptation. Integrating our observation with the current literature, we demonstrate how EGLN1 could qualify as a molecular equivalent of tridosha that can modulate different phenotypic outcomes, where hypoxia is a cause or a consequence both during health and diseased states. Our studies affirm that integration of the trisutra framework through Ayurgenomics can guide the identification of predisposed groups of individuals and enable discovery of actionable therapeutic points in an individualized manner

Population history and genome wide association studies of birth weight in a native high altitude Ladakhi population

Pathological low birth weight due to fetal growth restriction (FGR) is an important predictor of adverse obstetric and neonatal outcomes. It is more common amongst native lowlanders when gestating in the hypoxic environment of high altitude, whilst populations who have resided at high altitude for many generations are relatively protected. Genetic study of pregnant populations at high altitude permits exploration of the role of hypoxia in FGR pathogenesis, and perhaps of FGR pathogenesis more broadly. We studied the umbilical cord blood DNA of 316 neonates born to pregnant women managed at the Sonam Norboo Memorial Hospital, Ladakh (altitude 3540m) between February 2017 and January 2019. Principal component, admixture and genome wide association studies (GWAS) were applied to dense single nucleotide polymorphism (SNP) genetic data, to explore ancestry and genetic predictors of low birth weight. Our findings support Tibetan ancestry in the Ladakhi population, with subsequent admixture with neighboring Indo-Aryan populations. Fetal growth protection was evident in Ladakhi neonates. Although no variants achieved genome wide significance, we observed nominal association of seven variants across genes (ZBTB38, ZFP36L2, HMGA2, CDKAL1, PLCG1) previously associated with birthweight

Whole genome expression and biochemical correlates of extreme constitutional types defined in Ayurveda

<p>Abstract</p> <p>Background</p> <p>Ayurveda is an ancient system of personalized medicine documented and practiced in India since 1500 B.C. According to this system an individual's basic constitution to a large extent determines predisposition and prognosis to diseases as well as therapy and life-style regime. Ayurveda describes seven broad constitution types (<it>Prakriti</it>s) each with a varying degree of predisposition to different diseases. Amongst these, three most contrasting types, <it>Vata</it>, <it>Pitta</it>, <it>Kapha</it>, are the most vulnerable to diseases. In the realm of modern predictive medicine, efforts are being directed towards capturing disease phenotypes with greater precision for successful identification of markers for prospective disease conditions. In this study, we explore whether the different constitution types as described in Ayurveda has molecular correlates.</p> <p>Methods</p> <p>Normal individuals of the three most contrasting constitutional types were identified following phenotyping criteria described in Ayurveda in Indian population of Indo-European origin. The peripheral blood samples of these individuals were analysed for genome wide expression levels, biochemical and hematological parameters. Gene Ontology (GO) and pathway based analysis was carried out on differentially expressed genes to explore if there were significant enrichments of functional categories among <it>Prakriti </it>types.</p> <p>Results</p> <p>Individuals from the three most contrasting constitutional types exhibit striking differences with respect to biochemical and hematological parameters and at genome wide expression levels. Biochemical profiles like liver function tests, lipid profiles, and hematological parameters like haemoglobin exhibited differences between <it>Prakriti </it>types. Functional categories of genes showing differential expression among <it>Prakriti </it>types were significantly enriched in core biological processes like transport, regulation of cyclin dependent protein kinase activity, immune response and regulation of blood coagulation. A significant enrichment of housekeeping, disease related and hub genes were observed in these extreme constitution types.</p> <p>Conclusion</p> <p>Ayurveda based method of phenotypic classification of extreme constitutional types allows us to uncover genes that may contribute to system level differences in normal individuals which could lead to differential disease predisposition. This is a first attempt towards unraveling the clinical phenotyping principle of a traditional system of medicine in terms of modern biology. An integration of Ayurveda with genomics holds potential and promise for future predictive medicine.</p

Western Indian Rural Gut Microbial Diversity in Extreme Prakriti Endo-Phenotypes Reveals Signature Microbes

Heterogeneity amidst healthy individuals at genomic level is being widely acknowledged. This, in turn, is modulated by differential response to environmental cues and treatment regimens, necessitating the need for stratified/personalized therapy. We intend to understand the molecular determinants of Ayurvedic way (ancient Indian system of medicine) of endo-phenotyping individuals into distinct constitution types termed “Prakriti,” which forms the basis of personalized treatment. In this study, we explored and analyzed the healthy human gut microbiome structure within three predominant Prakriti groups from a genetically homogenous cohort to discover differentially abundant taxa, using 16S rRNA gene based microbial community profiling. We found Bacteroidetes and Firmicutes as major gut microbial components in varying composition, albeit with similar trend across Prakriti. Multiple species of the core microbiome showed differential abundance within Prakriti types, with gender specific signature taxons. Our study reveals that despite overall uniform composition of gut microbial community, healthy individuals belonging to different Prakriti groups have enrichment of specific bacteria. It highlights the importance of Prakriti based endo-phenotypes to explain the variability amongst healthy individuals in gut microbial flora that have important consequences for an individual's health, disease and treatment

Konservasi Tanaman Lada (Piper Nigrum L.) Secara in Vitro

In vitro conservation of black pepper (Piper nigrum L.)Black pepper (Piper nigrum L.) is one of the economically im¬ potant spices. The major constraint in black pepper cultivation and conservation in ield is foot rot disease caused by Phytopthora capsici which could cause plants die. Conservation of black pepper germplasms as living collections in ield is risky due to pests and natural disaster. The experiment on in vitro cop ervation of black pepper var. LDL was conducted al the laboratory of Plant Genetic Resources and Breeding, Research Institute for Spice and Medicinal Crops (RISMC) Bogor from April 1998 to Maret 1999. Single node cuttings from sterile culture were used as explains. The explains were cultured on Murashige and Skoog (MS) medium on full and half strength concentration supplemented with paclobutrazol (paclo) (0, 1, 3 and 5 mg/1). The experiment was performed in a randomized complete block design arranged factorially with 10 replications. The result showed that the medium supplemented with paclo on both full MS and MS A medium could suppress vegetative growth until 12 months. There was no signiicant interaction between medium and paclo on shoot initiation. The effect was signiicant on shoot height, number of leaves and culture performances. Increasing paclo concen¬ tration caused higher suppression of plant growth. MS A medium supplemented with paclo 5 mg/1 showed the slowest growth with shool height 2.10 cm and number of leaves 9. Culture performance was fresh, with green leaves and vigorous. Advcntive shoots were able to regenerate on the medium supplemented with BA 0.3 mg/1. In vitro conservation of black pepper with paclo did not change plant regeneration ability. Therefore, this technique may be used as an altenative method for black pepper conservation

Additional file 5: of Combined genetic effects of EGLN1 and VWF modulate thrombotic outcome in hypoxia revealed by Ayurgenomics approach

Allele frequency differences between Prakriti types and IE pool

Additional file 3: of Combined genetic effects of EGLN1 and VWF modulate thrombotic outcome in hypoxia revealed by Ayurgenomics approach

Total scores of protective alleles in combined genotypes of VWF and EGLN1 in high altitude and a genetically related low altitude population in India

Additional file 6: of Combined genetic effects of EGLN1 and VWF modulate thrombotic outcome in hypoxia revealed by Ayurgenomics approach

Association of SNPs varying between Prakriti with selection pressures such as climatic conditions, mode of subsistence, pathogen pressure and cultural practices (source: http://genapps2.uchicago.edu:8081/dbcline/ )

Heart rate variability during head‐up tilt shows inter‐individual differences among healthy individuals of extreme Prakriti types

Abstract Autonomic modulation is critical during various physiological activities, including orthostatic stimuli and primarily evaluated by heart rate variability (HRV). Orthostatic stress affects people differently suggesting the possibility of identification of predisposed groups to autonomic dysfunction‐related disorders in a healthy state. One way to understand this kind of variability is by using Ayurvedic approach that classifies healthy individuals into Prakriti types based on clinical phenotypes. To this end, we explored the differential response to orthostatic stress in different Prakriti types using HRV. HRV was measured in 379 subjects(Vata = 97, Pitta = 68, Kapha = 68, and Mixed Prakriti = 146) from two geographical regions(Vadu and Delhi NCR) for 5 min supine (baseline), 3 min head‐up‐tilt (HUT) at 60°, and 5 min resupine. We observed that Kapha group had lower baseline HRV than other two groups, although not statistically significant. The relative change (%Δ1&2) in various HRV parameters in response to HUT was although minimal in Kapha group. Kapha also had significantly lower change in HR, LF (nu), HF (nu), and LF/HF than Pitta in response to HUT. The relative change (%Δ1) in HR and parasympathetic parameters (RMSSD, HF, SD1) was significantly greater in the Vata than in the Kapha. Thus, the low baseline and lower response to HUT in Kapha and the maximum drop in parasympathetic activity of Vata may indicate a predisposition to early autonomic dysfunction and associated conditions. It emphasizes the critical role of Prakriti‐based phenotyping in stratifying the differential responses of cardiac autonomic modulation in various postures among healthy individuals across different populations