Epidemiological Quad: Microbiome, the Fourth Dimension
Year: 2025
Type: article
Abstract: “Medical science has made such tremendous progress that there is hardly a healthy human left.” — Aldous Huxley.[1] The current practice of medicine is being navigated by an abundance of information, data, evidence, and their applications—often aided or abetted by artificial intelligence.[2] Successful treatment is incumbent upon defining the aetiopathogenesis of the presenting illness. Traditionally, the epidemiological triad (ET) has been the its foundation. The concept of ET, a bedrock of medical practice, enunciated by Stevens RB, a plant pathologist, was applied to human disease by Wade Hampton Frost.[3,4] There is an additional dimension to the Host, Pathogen, and Environment arms of ET: the environment we carry on our body and the environment within our body, thus forming an Epidemiological Quad (EQ). This fourth dimension of EQ consists of a diverse ecosystem of microorganisms, the microbiome. The microbiome numbers overwhelm the number of our own cells, by manyfold. The microbiome’s genomic content is a further multiple of our total genomic material. This diverse microbiome makes us a ‘superorganism’.[5] The microbiome of our existence as a superorganism has been primarily studied through our gut microbiota. Identification of the diverse microorganism species was previously limited by laboratory-based sampling, culture, and identification techniques. This process has been expedited by sequencing of PCR-amplified 16S ribosomal mRNA, used for phylogenetic classification of bacteria.[6] Our microbiome, acquired by us as a fetus, evolves to stabilize by the age of 3 years.[7] Initially thought to be acquired at birth, it has been reported to colonize during gestation and is living in spaces considered sterile, such as the kidneys.[8,9] Integrity of a stable microbiome ecosystem is essential for health. Any disturbance in the microbiome, known as dysbiosis has been implicated in disease states, ranging from behavioural disorders and personality to a plethora of benign and malignant diseases. It has been found to have defined molecular pathways for inflammatory and immunologic responses.[10,11] These pathways have been shown to modulate sterile inflammatory responses, communicate with distant organs via molecular signals, communicate across the gut via the Vagus nerve, modulate cytokines, help produce hormones, maintain immune competence, and act as internal pharmacies for essential peptides and oncoprophylactic molecules.[12,13] Prof. Stig Bengmark, in 1993, working at the University of Lund, cultured microbiota from human faeces, the strains of the cultured species, that could colonize our intestines. He coined them as probiotics and linked them to post-surgical sequelae including postoperative adhesions. He reported the importance of microbiome-friendly/rich enteral feeds necessary before surgery and as early as possible after surgery.[14] The first probiotics were associated with natural fermented foods like Dahee (Indian fermented milk preparation) and were not viewed as medicines until defined by the World Health Organization as “Live microorganisms, which when administered in adequate amount confer a health benefit on the host.”[15] The use of probiotics in abdominal and colorectal surgeries has added to the benefits of the ERAS (Enhanced Recovery After Surgery) doctrine. Probiotics including those from traditional Indian diets, have been shown to improve convalescence, patient-reported outcomes, early recovery from paralytic ileus, reduce surgical site infections, anastomotic leaks, and antibiotic-associated diarrhea.[16–20] The lead taken by surgeons in studying and applying the benefits of the microbiome is a testament to surgeons being role models and leaders of innovation and social change.[21,22] The symbiosis of these microbes defining our superorganism’s state in disease or health, is an example of health being related to nature. It goes beyond the frontiers of climate control and conservation of Earth’s resources. Human civilization has evolved over millennia with accumulation of wisdom towards progressively improving ecosystems. The oldest records of human civilization encapsulate the wisdom about human interaction with the environment, around, on and within us, in prayers called Shanti Mantra.[23] It reads as follows:Om Dyauh Shaantir-Antarikssam Shaantih Let there be peaceful coexistence in the environment, peaceful coexistence in the cosmos.Prithivi Shaantir-Aapah Shaantir-Oshadhayah Shaantih | Vanaspatayah Shaantir Peace on Earth, peace in waters, peace among flora and fauna.Vishvedevaah Shaantir-Brahma Shaantih Peace among the powerful, peace among innovators and researchers.Sarvam Shaantih Shaantir-Eva Shaantih Saa Maa Shaantir-Edhi Peace everywhere; peace and only peace—bestow peace upon all.Om Shaantih Shaantih Shaantih Bestow, hail peace—only peace and holistic peace. Science has progressed at an inspirational pace, yet much remains unknown or not understood despite being within the realms of our everyday experience and observation. Simple acts of fellow living beings like locomotion in insects and birds, sonars of bats and dolphins, or energy-matter interchangeability amongst in living plants etc. evades our best efforts to reproduce them with equal efficiency.[24] Indian civilization believes in the universal connection of everything, living and non-living, with everything existing, being essential for existence. It revers the elements like air, water, and earth as living beings with voices of their own. Science is taking cognisance of this belief. We are now studying the pulse, the beat, the message that Mother Earth is sending us every 26 seconds. The message first recorded in the 1960s continues to test the best scientific brains.[25] Julian Treasure, a top-rated communication trainer, reminds us: “The Hindus say ‘Nada Brahma,’ which means ‘The world is sound’ and it’s true because everything is vibrating.” Accumulated civilizational wisdom, available to us for eons, could not be studied for wider scientific application, due to barriers like language, geopolitics frontiers, and cultural crossroads. The knowledge has been lost in translation, interpretation, or dialects. Translation of such ancient knowledge demands being agnostic to existing biases, logical or methodological, semantics, ontological or epistemological. Simple literal translations change the meanings, message and matter completely. “Poetry is what gets lost in translation”, is an apt reminder from Robert Frost. George Eliot said, “All meanings depend on the key of interpretation”. Friedrich Nietzsche reinforced the need for an holistic and objective equipoise in evaluating divergent interpretations “All things are subject to interpretation. Whichever interpretation prevails at a given time is a function of power and not truth.” We, have an opportunity to study our heritage with current methodologies, and integrate the time tested wisdom for the best results in our practice. Surgeons have been known as “Imagineers”—imagination-driven engineers working on fellow beings, amidst constantly evolving machines and AI systems, which at times pose a challenge to the inherent human interaction involved in “informed consent.”[26–28] We owe it to our civilizational mentors, to translate the wisdom for the benefit of mankind apart from getting credit back to its rightful person. Otherwise, science will suffer the guidance of figures like Andreas Vesalius, Michael Servetus, Ignaz Semmelweis, Erich Muhe, and Indian greats like Sushruta, Charaka, Aryabhatta, and Bhaskaracharya.[22] The world will continue to believe that Vasco da Gama discovered the sea route to India, unless we translate and publish his own diary, which records a ship thrice the size of his ship, guiding him, which belonged to an Indian spice merchant named Chandan.[29,30] We possess a treasure trove of literature which science is beginning to explore and understand now. Indian cuisine and kitchen practices have a menu of naturally fermented foods. Understanding the fourth dimension of EQ is validating the microbiome diversity in our meal ingredients like spices, curry and snacks like Pani-Poori, Dahee etc. We must apply our heritage based science for improving outcomes in our surgical practice with due scientific and hygiene diligence. We have always been keenest observers of nature, students of nature, and dutifully grateful to nature in our Vedic prayers. As the western intellectual and comedian, Stephen Fry reminds us: “If you look out of the window and find nothing man-made there, the view will always be unconditionally beautiful.” Let us complete the understanding of health and disease states, by applying the science behind the fourth dimension of EQ, the Epidemiological Quad. Our endeavours should work towards aligning the practice of medicine to nature. Aligning the nature to superorganism state of an individual by respecting their eating habits, lifestyle, culture, and cuisine. Let us not dictate their food and kitchen choices as most of modern medical dietary advice is based upon understanding of Western climate, diet, cuisine and lifestyle. Resurgence of faith in Desi Ghee (clarified butter) is a testimony of same, as to a largely vegetarian population, Desi Ghee and milk products are the solitary source of animal fat and its microconstituents. Dahee, fermented rice, and sambar are better for our geography as compared to necessities of west, recommending pre-operative ‘high-carbohydrate,’ drinks or probiotics in various forms. Modern medical practice is facing another challenge from the increasing number of patients presenting with multi-system health complaints. Current practices based on education programmes and literature, mostly provided by industry, result in patients visiting battery of specialist receiving a cocktail of medicines. Many of these patients needing optimisation of their superorganism status are veered to seek pharmacotherapy, to finally being labelled as “nut cases” or psychiatrically disordered. As Genius critiques: “A practice long on style but short on science by erudite medicos, imbued with wisdom of vino and abusing patients by calling them nuts.”[31] This is a reminder to civilizations as ours, to share all its wisdom, conviction in universal coexistence being paramount. The superorganism with the fourth dimension of EQ disturbed, suffers from compartmentalisation of pursuit of healthy existence, into conservation of resources, climate literacy, care of plants, water bodies and now the big ticket darling of industry “probiotics.” Indian civilisation practiced the human being being a superorganism in perfect harmony with cosmos, all living beings, environment as well as the fourth dimension of EQ (4dEQ), the environment on and within ourselves. This is the essence of everything, being connected, the universal consciousness, the universal soul, the mantra of universal coexistence, the 4dEQ. Microbiome is the currency of same for practitioner of medicine. Healthcare should incorporate the understanding about not only chromosome but exposome as well —the Fourth Dimension of the Epidemiological Quad, 4dEQ. The use of probiotics based on Microbiome studies is an evolving science. It should be used with caution and better be avoided in vulnerable populations like newborns, pregnant women, and immunocompromised or people on immunosuppression.[32] This vulnerability reinforces the harmlessness of probiotics in our culture and cuisine. We have had encouraging experience in recommending sweet Dahee and Pani-Poori drink as a substitute for the recommended high carbohydrate drinks pre-operatively. Natural kitchen ingredients and foods have a transgenerational test of their harmlessness among families. We should incorporate them before pushing industry advocated concoctions specially for the vulnerable populations. Our social accountability demands that as a minimum from us.[33] Respect to an individual patient’s culture and cuisine in our practice, goes a long way not only in social accountability but in enhancing goals of ERAS. Incorporation of 4dEQ based benefits in respecting so will be a good beginning to reap more benefits as our understanding of microbiome and superorganism evolves.
Authors: Brij B. Agarwal, Palak Nayan Agarwal, Siddharth Glida, S. Sarvesh, Vasu Vashishtha
Institution: Sir Ganga Ram Hospital
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4410852858