A Clarion Call or a Call of the Clarions

“Epidemiological Quad: Microbiome, the fourth dimension,” A timely editorial to highlight one of the most researched and discussed topic, its importance to our profession and most likely the future of medicine as we learn more about our genetic code, the role of cellular proteins with respect to health and disease. Agarwal et al. describe an Epidemiological Quad to extend our concept of host, pathogen, and environment regulating our health.[1] The original concept of milieu interieur as researched and promulgated by the physiological experiments of Claude Bernard extending the work of Charles Robin, this was in parallel to Virchow’s focus on the cell, von Rokitansky and Eppinger’s work on microcirculation followed by Alfred Pischinger description of the extracellular matrix, role of hormonal and autonomic nervous systems forming a complex system of regulation for the body as a whole and for cellular functioning. In the words of Claude Bernard, “the stability of the internal environment is the condition for the free and independent life.”[2] This concept was the basis of medical teaching and the goal to be achieved. The concept received a jolt with the use of a long forgotten concept dating back to 4th century China when “yellow soup” was used to treat severe diarrhea and food poisoning, documented again in the 16th century by Li Shizhen, a Chinese medical expert. This forgotten concept resurfaced in modern medicine when Dr. Ben Eiseman (1958) used fecal microbiota transplantation (FMT) to successfully treat patients with Clostridium difficile diarrheal infections. In the 2000s, the rise of antibiotic-resistant infections, FMT gained the recognition as a highly effective treatment for recurrent C. Diff infections. In 2013, the FDA classified FMT as an investigational therapy, prompting an increase in clinical, basic science research, with FMT evolving into gut microbiome transplants, giving us advanced donor screening, capsule-based delivery, and microbiome engineering. Research, exploring the finer details and isolation of healthy bacteria, which may help us customize gut microbiota to treat specific diseases. The list of applications has gone from treatment of recurrent resistant C. Difficile diarrhea to treatment of IBD, IBS, autoimmune disorders, obesity and metabolic syndrome, and even neurological disorders from autism, Parkinson’s, and depression. The field has exploded as the microbiota has proven to be an ally. Back to the future, the discovery of an old Chinese experiment has given birth to a new industry of studies, research, and application; the microbiota or the microbiome. What did we miss or where did we go wrong is the question to the whole scientific community. We focused all our research and energy on reestablishing the “milieu interior” using our biochemical information and the bright lights of the OR, the exhilaration of changing anatomy with advances in anesthesia as the anthem of medical healing. We forgot the basic knowledge of embryology, physiology, and immunology. We forgot the human body is a tube within a tube with the endoderm (inner) and ectoderm (outer) representing the two surfaces within which our organs reside: these surfaces are our first line of defense against the ravages of disease. We forgot physiology as we advanced in surgical techniques, micro dissection and less invasive surgery thru scopes and help of robots, that once the human/robotic hand altered the anatomy it changed the native physiology (the human body never being the same) and we finally never completely understood and applied the knowledge of our most complex system; the largest immune organ which controlled how we trained our lymphocytes, how we monitored both regenerative and noxious proteins, how we absorbed our nutrients and altered our receptors and what it took to maintain the health of this most delicate barrier and line of defense. We forgot our co-inhabitants; the families of bacteria that we now call THE BIOME, that resides with in us but still outside. The last few decades have witnessed an implosion in studying the biome, how to keep it healthy, how to replace it in sickness, and how to normalize it pre- and postoperatively as the altered anatomy and physiology ravage the healthy and promote the unwanted. We are re-learning the advantages of low-grade infections, maintaining a healthy immune system in the gut, and preventing transmigration of infection. How the dysregulation of the GI biome by highly processed foods, microplastics, antibiotics, chemotherapy, targeted immunotherapy, altered anatomy, and motility results in poor outcomes despite our best efforts. Similarly, the exposure of chemicals in the form of soaps, oils cosmetics have altered the ectodermal microbiome, which needs to be protected not just for good surgical outcomes but also to minimize the burden of dermatological pathology. We have come to the simple conclusion: we are wholesome when we respect our co-inhabitants. How do we achieve that? Dr. Agarwal et al.[3] point to the age-old foods and basic skin care to maximize our health and outcomes of care. Currently progress in civilized society leads to the consumption of foods proving to be unhealthy in salt, sugars, cereal and unhealthy fats (shelf life), hence the epidemic of obesity globally; now considered a chronic inflammatory condition, resulting in dysregulation of the gut immune system with activating the Th 1 response, experimental infection with low dose helminthic load, activates the Th 2 response dampening the Th 1 activity, renormalizing the altered Th 1-induced insulin signaling and associated resistance as discussed by Giocomin (Annual review of Immunology 2021). This points us to the future of therapies and recognition finally of the importance of the ectodermal and endodermal biome. The complexity of the research is in the simplicity of the recognition of our embryology and our interface with nature and nutrition. Yes, it is a clarion call; the war for our health has changed direction. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.