The grand Indian plan that could change all things medical4 months, 14 days ago
India is getting ready for a project that is as small as it gets — and as big. The Human Microbiome Project (HMP) will map trillions upon trillions of microbes — bacteria, fungi, viruses, archaea — that are found in Indians. On their skin. In the dark depths of their guts. Swarming on every inch of their body.In a one-of-a-kind project in the country, researchers will take skin and oral swabs and collect blood and faecal samples from 20,600 individuals who belong to 103 endogamous communities (which marry within the group). These will include 32 tribes as well — from Changpa in Ladkah to Warli in Maharashtra and Mankidia in Odisha, and from Ao in Nagaland to Koya in Telangana. After collecting the samples, scientists will sequence the genome of these microorganisms.
(These microbes are called human microbiota and their genetic material are collectively referred to as the human microbiome.) The Union government-funded, Rs 150 crore project could get underway in the next few months, once the Department of Biotechnology gives it the nod. It wants to map the microbiome composition of India’s different communities — and how genetics, diet and environment impact it differently.The ambitious project aims, at the end of it, to generate the baseline microbiome data of Indians. It will also define the core microbiome of tribal populations that are unaffected by modern lifestyle. It will even help us understand the links between microbial composition and disease risks and also create a repository of microbial samples from healthy individuals to help develop probiotic-like solutions.
The HMP is a collaborative effort between 11 research institutes and universities across the country, both public and private, including the All India Institute of Medical Sciences in New Delhi, the Insitute of Advanced Study in Science and Technology in Guwahati and Symbiosis International University in Pune. The study is being led by Pune’s National Centre for Microbial Resource (NCMR), which is part of the National Centre for Cell Science.“It’s a three-year project, but its repercussions will be there for many years to come,” says Yogesh Shouche, principal investigator at NCMR, in his office in Pune. Shouche, who has researched microbes for two decades, says this project is more challenging than similar projects in the West — for instance, in the US, Britain and European Union. “Unlike in India, microbiome projects in the West work with genetically more homogenous populations whose dietary patterns are more or less uniform.” India’s diversity is staggering on many counts.According to a study by the National Institute of Biomedical Genomics in Kalyani, near Kolkata, which is also involved in HMP, modern mainland Indians have descended from four ancestral populations — Indo-European, Dravidian, Tibeto-Burman and Austro-Asiatic — and not two as earlier estimated. Indians’ diets also vary. For instance, according to a 2014 Union government survey, nearly 99% of Telangana’s population eat meat, while only a quarter of those in Rajasthan do so. A comparison of urban and rural populations in HMP will also yield insights into changes in microbiota, if any, from consumption of processed foods, which is higher in cities.“It will be interesting to study the links between microbiota and environment and diets,” says Rakesh Sharma, senior principal scientist at the New Delhi-based Institute of Genomics and Integrative Biology.Gut InstinctsIt is the microbe that could unlock our understanding of diseases, disorders and differences but there is no definitive figure for the total number of microbes in a human body. We know that dominant among them are bacteria, a majority of which are found in the gut, especially the large intestine or colon.One estimate by researchers at Israel’s Weizmann Institute of Science and the Hospital for Sick Children in Toronto, Canada, pegs the total number of bacteria in a human body at 40 trillion, compared with 37 trillion human cells. The total number of bacterial genes in the gut outnumber human genes by at least 30:1. Gut bacteria, which are the most extensively studied among human microbiota, help in breaking down undigested nutrients, producing vitamins and controlling disease-causing bacteria.India is already quite late to the microbiome research race. The Human MetaGenome Consortium Japan began in 2005 and the US Human Microbiome Project two years later. The US also announced a National Microbiome Initiative in 2016, committing a government investment of $121 million for two years and private investments of $400 million over an unspecified period. Similar initiatives can also be found in Canada and the European Union.
There are also projects like the American Gut project and, its offshoot, the British Gut project. They have received $2.5 million in individual contributions (as of May 2018) and crowdsourced samples from over 11,000 people (as of mid-2017). Among the observations made by American Gut were that those who had more than 30 plant types a week had more diverse gut microbiomes and fewer antibioticresistance genes than those who had 10 or fewer a week. Moreover, those who had antibiotics in the past one month had less diverse microbiota than those who had not had antibiotics for a year.Antibiotic use is one of the causes, along with staying in a healthcare facility, of Clostridium difficile (C diff ) infections, whose symptoms include diarrhoea, nausea, fever and dehydration which could be life-threatening. Antibiotics kill both good and bad bacteria, but if they kill more of the good bacteria, it could aid the growth of bacteria like C. diff. The study of gut microbe, for instance, has had interesting results. The first randomised controlled trial in C diff infection, published in 2013, showed the efficacy of faecal microbiota transplant (FMT), in which faecal bacteria from a healthy donor is transferred to a patient, usually through colonoscopy.Bhabatosh Das, assistant professor at the Translational Health Science and Technology Institute, Faridabad, believes people living in rural areas make for ideal donors. “Their guts have very diverse bacteria, while in urban areas fast food and antibiotics result in reduced diversity.”
There are attempts being made to use FMT for obesity too. Dysbiosis, or an imbalance in the gut microbial composition, has been associated with obesity. According to a study published in Nature magazine in October 2018, FMT from mice, that were fed a normal-fat diet, to mice that were given a highfat diet resulted in beneficial effects usually caused by diet and exercise. Another study, also published in Nature, in April 2018, found that mice that were given chemotherapy and anitbiotic treatment regained their pre-treatment microbial composition after being given FMT.In another study from 2017, 34 pairs of twins were assessed, in which only one of every pair had multiple sclerosis. More of the mice which were given gut microbes from the twin with MS developed a disease similar to MS than those which got microbes from the healthy twin. Poor microbial diversity has also been linked to inflammatory bowel disease and Type 1 diabetes. But there are still questions. “We can’t say whether diabetes is driving gut microbes or vice versa,” says Dr CS Yajnik, a diabetologist in Pune.Mind & MicrobeThe other area where a lot of research is focused is the relationship between microbiome and mental health. In a 2013 study by scientists from the California Institute of Technology and Baylor College of Medicine, Houston, they found that when mice with symptoms similar to autism were given the bacterium Bacteroides fragilis, their microbiomes changed and they became more communicative and less anxious.The American Gut project also observed that some types of bacteria may be more common in people suffering from depression than those who are not. It also found in an assessment of the gut microbiomes of 125 people — who claimed to have a mental health disorder, like depression, post-traumatic stress disorder, schizophrenia or bipolar disorder — that their microbiomes had more in common with each than with that with someone of the same age, gender, country and body mass index.
Moreover, babies born through natural birth tend to pick up microbes from the mother’s vagina and bowel, which could make them less likely to develop asthma, Type 1 diabetes, obesity and allergies. Similarly, breast milk is crucial to the microbial composition in kids’ guts. While the human microbiome is getting a lot of attention these days, with reports of studies uncovering the relationship between the microbiome and a disease or disorder. But there are some who sound a word of caution and believe that the significance of the microbiome may be overstated.“The hypothesis that variation in the gut microbiota can explain or be used to predict obesity status has received considerable attention and is frequently mentioned as an example of the role of the microbiome in human health…(but) we found that although there is an association, it is smaller than can be detected by most microbiome studies,” said a metastudy of 10 papers, published in August 2016 in mBio, a journal published by the American Society of Microbiology.It is quite possible that some of the recent findings about the role of microbes in our health may be disputed by future research. But a project of the scale and scope of the Human Microbiome Project could definitely advance our understanding of the complex world of human microbiota and what we do to each other.
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