Abstract
We humans have been explorers for a long time. We have always been looking to explore new places & civilisations, but we never felt a need to understand the deep rooted ecosystem of organisms living on & inside of our body-trillions of microbes.
These groups of microbes, also referred to as microbiota, are similar to us in many ways. They grow like we do, food we eat is a fuel for them that gives them energy & they interact the way we do.
During millions of years of evolution inside our body, they have found a fascinating way to communicate with us through multitude of biochemical signals that has shaped our biology for good or worse.
These trillion microbes have co-existed with us & transformed our approach towards nutrition, medicine, hygiene & environment. Epigenetically our body’s ability is limited to perform all biological functions & therefore our body has outsourced a number of biological functions to these microbes
Right from metabolizing food, giving us nutrients, producing neurotransmitters & hormones, training our immune system to differentiate between friend or foe, communicating with our brain, neutralizing pathogens, regulating satiety & blood sugar & more, microbes living at different sites inside our body does all & holds key to our health.
Like a good leader, microbes let us believe that we are taking all the biological decisions, however it is these microbes who are pulling all the strings.
Transformation of human biology landscape
We have been nomads moving in small groups & hardly came in contact with each other. Therefore microbes inside of us were living in heaven. Then three major changes- agriculture, urbanisation & globalization changed entire human biology landscape for worse.
- Agriculture-With agriculture, livestock became domesticated & crop cycle became predictable. We became permanent settlers & started coming in contact with each other more frequently. As a result we started sharing microbes with each other & even started consuming animal protein. This changed the entire ecosystem of the human microbiome.
- Urbanization:This led to more interconnection between the people & exchange of microorganisms & pathogens & we started developing infections. As a result, scientists & doctors developed antibiotics to fend off these infections. Although these antibiotics were effective in killing off infections, it also disturbed & imbalanced the entire human microbiome, thereby making us develop chronic diseases. Type 2 diabetes, which was a rare phenomenon, became a regular affair. The solution for infections was the root cause of development of most, if not all, chronic diseases. Demand for more urbanization led to a shortfall of areas for agriculture production. This posed challenges with regards to procurement of food & led to major social & environmental shifts.
- Globalization: This environmental shift was met by Globalization. This increased the mobility & we could move from one country to another in a space of a few hours. This led to further exchange of microorganisms through trade & travel.
Shortage of agriculture production led to corporatisation of the food system with increased supply of empty calorie foods. In order to reduce cost & meet increasing demand, there was an endless supply of foods laden with sugar, salt, artificial sweeteners, hydrogenated oil & harmful chemicals. These harmful ingredients started killing our microbes & the number of people developing chronic diseases accelerated.
The flaw in the current healthcare system
Our current healthcare system as we see today is the best we have when it comes to infectious & episodic diseases &/or trauma. If someone has an infection, he/she can get antibiotics to get rid of them. But the system was never designed to address chronic diseases. Medical schools never included microbiome & nutrition as part of their curriculum & best doctors can do is to marry symptoms with drugs which is just a way of managing symptoms of chronic diseases but not preventing or curing them.
The healthcare system has built a number of standard of care plasma level diagnostic tests that gives a simplistic view of post mortem or executive summary of various biological processes & deregulation in terms of multiple biomarkers but fails to find out the root cause & cannot measure changes in biology & chemistry before & during the disease onset. Besides, these tests never take into account the functions of trillions of micro-organisms living in the gut, mouth, vagina, skin & more, representing 99% of biology.
The last few decades have seen advancement in technology. Human Genome was sequenced two decades ago in US & it started in 2020 in India, we have built supercomputers that could process petabytes of data & have seen advent of new age wearables that uses advanced sensor to track various health parameters such as Blood Glucose Level, Heart Rate, Sleep & more but still we are dealing with epidemic of chronic diseases. Some facts & figures.
- Globally, 41 million people die of chronic diseases every year
- > 55 million people suffer from dementia worldwide
- Global incidence of Non- Alcoholic Fatty Liver Disease(NAFLD) is 47 for every 1000 people
- 100 million plus Indians are either prediabetic or suffering from type 2 diabetes
- 13% of Indian population have high risk of cancer
- 10% of Indian population suffers from chronic kidney disease; Renal failure is detected at a late stage & most of the patients end up in dialysis with no curtative solution
- Diseases such as NAFLD, Oral & Throat Cancer & Dementia are hard to detect & the list goes on.
Millions of dollars have been spent on making pharmaceutical drugs to manage the diseases but not on the application of science & technology, which we already have at our disposal, to understand the pathogenic processes involved in onset & progression of chronic diseases & cancer.
In order to place chronic diseases as a chapter in history books, we have to just put our resources in adopting altogether a different approach in practicing science & technology.
The gap in the current scientific approach
Since the human genome project was completed followed by the Genome India Project which started in 2020, scientists have focussed on human gene studies. However, it is yet to churn out any preventive or curative solutions to pressing chronic health issues. This is not astonishing as chronic diseases are not related to genetic codes. Even if genotype indicates risk of a particular disease, it is an external trigger- either nutrition,stress or the environment that leads to disease onset, remission or relapse. DNA has a miniscule role to play in chronic diseases.
Similar logic applies to microbiome DNA & taxonomy. Human body is a sack of thousands of biochemical reactions. Name of a bacteria, fungi, yeast, protozoa or virus does not say anything about the source code of chronic diseases. The functions performed by these microbes & genes they express are a better indicator of the underlying cause of chronic diseases. For Instance, Porphyromonas gingivalis is one of oral microbes implicated in the onset of periodontal disease. However this microbe lives inside our mouth as commensals & 88% of adults have this microbe in their mouth. However not everyone has periodontal disease. It is an external trigger that triggers expression of virulence genes coded by this microbe & makes it pathogenic. To really decode the impact of microbiome on our health, we have to move away from taxonomy /microbial DNA & focus on their functions & genes expression levels. Unfortunately, the most widely used sequencing method-16S rRNA gene sequencing has a number of biases & poor resolution in microbially expressed functions & taxonomy.
The present practice of clinical research is research grade & lacks vigor in collecting & analyzing the right data sets. There are a number of biases in collecting data sets & chances of false positive or negative cannot be ignored.Besides, these clinical research projects are restricted to individual biological parameters- a single gene or protein, restricting research to one hypothesis. These research practices does not consider entire human body as one single constituent
There is a need to move away from hypothesis driven approach
New approach to health & disease- System biology focussed on blend of scientific discovery & technology rather than research publications only
In order to understand the mechanics of chronic diseases, we need to transform the entire healthcare system from symptoms management to preventative & personalized care. To achieve this feat, we really need to apply science & technology to measure the changes in the web of molecular pathways including microbial, metabolic & immunologic that trigger onset & progression of chronic diseases & cancer.
In order to truly understand disease progression, the following novel scientific approach should be adopted
- We should move away from both human DNA & microbial taxonomy & rather focus on downstream functions by measuring RNA, metabolites( produced by microbiome) or proteins.
- A comprehensive blend of measuring human genes expression & microbial genes expression is the way forward as each of these aspects contributes towards illness. A System biology approach that considers each of these parameters & their interaction with the environment is the way forward.
- We should strive to collect huge molecular data sets from broader population covering human & microbial genes expression using next multi omics technology, process them using cloud computing based advanced bioinformatics tools & analyze & compress them into various molecular pathways using machine learning to compute precision nutrition /therapeutics interventions to eliminate the pre-disease molecules so that disease do not occur in the first place.
Citations
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4841510/
https://pubmed.ncbi.nlm.nih.gov/31322753/
https://gut.bmj.com/content/66/12/2087.citation-tools
https://www.nature.com/articles/s41467-019-12476-z
https://pubmed.ncbi.nlm.nih.gov/19234110/
https://www.nature.com/articles/s41579-018-0029-9
https://pubmed.ncbi.nlm.nih.gov/33692356/
