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Microbiome plays vital role in health and wellbeing
Our Bureau , Mumbai | Thursday, July 9, 2015, 08:00 Hrs  [IST]

The microbiome, the vast population of microbes that live within all of us play a vital role in our health and well-being.

Although microbiologists have known for many decades that everyone hosts resident bacteria, beneficial and malign, their diversity and biological significance are only now becoming clear as scientists deploy new techniques of molecular biology to probe the microbiome.

For centuries, it was thought that bacteria could only be harmful to us. But recent research has yielded insights into the microbiome's role in everything from our immune system to our metabolism.

Last decade, the National Institutes of Health began the Human Microbiome Project to study those trillions of bugs and their implications for human health—as it turns out, microbes make up the majority of cells on our bodies, outnumbering human cells 10 to 1. The average 200-pound person is covered in 2 to 6 pounds of micro-organisms, according to the NIH.

A healthy adult is made up of about 10 trillion human cells; microbial cells are smaller but there are 10 times more of them, weighing in at 3lb in total, roughly the same as the brain. The revelation that each of us depends on our individual living world, with far more inhabitants than there are people on earth, is surely sensational.

Boom in research
In recent years, there’s been a boom in research on the human microbiome as scientists uncover its importance for our health.

Recent research shows that the hundreds of microbial species populating this teeming inner world play essential roles in the most fundamental processes of our lives, from digestion to immune response and even behaviour. Imbalances in the microbiome, caused by aspects of the modern lifestyle such as medication, sanitation and diet, have been linked with diseases from obesity and diabetes to asthma and eczema.

An imbalance in the composition of microbes in our guts is now believed to play a role in a staggering array of ailments and disorders, from allergies to autism, obesity and depression. It’s a paradigm shift that has sparked the hope of thwarting or treating such conditions by zooming in on our microbial inhabitants and figuring out what they do.

Yet making sense of the health claims is no easy endeavour. Scientists are still in the early stages of figuring out what bugs exist in our systems, never mind which we need for optimal health. And with few exceptions, the ability to fight or ward off disease with the right mix of microbes – or with the molecular compounds they produce – is still largely out of reach.

“Is there a perfect gut microbiome? … And can you improve it by taking probiotics? Those are questions that are being very definitely asked, and there is no final answer as of yet,” says Dr. John Bienenstock, a distinguished professor of pathology and molecular medicine at McMaster University.

Bienenstock is one of the several international scientists who contributed to a recent paper, published in the Annals of Medicine, that suggests our modern, urban lifestyle may be limiting our environmental exposure to an important diversity of micro-organisms. They believe the kinds of microbes we come in contact with, as early as in the womb and into our first years of life, are critical for normal immune development.

A variety of factors tied to modernity – including Caesarean births, formula-feeding, a lack of green space in cities, inadequate physical activity and the use of antibiotics – mean many of us aren’t coming in contact with the broad spectrum of micro-organisms that previous generations did. This could explain the rise of chronic inflammatory disorders in urbanized parts of the world, the paper says.

The solution, however, is more complicated than simply identifying “beneficial” bugs and re-introducing them into our lives. Researchers are long past viewing micro-organisms as “good guys and bad guys,” Bienenstock says. Rather, the microbiome is now understood to be a complex and bustling community, where even potentially disease-causing strains can be useful neighbours and friendly ones can turn against us.

“It’s the diversity that counts. The more different types of bugs that live together happily and communicate, the healthier you are,” he says.

Moreover, it appears the human microbiome is pretty much set by the age of two or three. That would mean, even though you can temporarily introduce new yeast and bacteria through your diet or reduce your existing microbial population with antibiotics, your microbiome will likely bounce back to its set profile. To achieve long-term benefits for chronic conditions, adults would likely need to constantly replenish their guts with the relevant missing microbes.

And while scientists have made strides in recognizing various strains of gut microbes by identifying their molecular DNA signature, they still have a long way to go to determine what each does and how each functions, Bienenstock says.

That hasn’t stopped people from making ambitious promises that leap ahead of the science. Products and advice abound, with claims about how to modify your microbiome for everything from achieving a glowing complexion and losing weight to reducing anxiety and preventing dementia. And people are taking steps beyond popping probiotic pills or eating yoghurt and fermented foods.

Enormous potential
Some have dubbed the microbiome a newly discovered organ, others an ecosystem. The potential for using the microbiome is enormous. It's long been known that micro-organisms populate the skin and gut, and that digestion requires them.

The microbiome interfaces between the human body and the outside world in complex ways, but the gist is that human DNA has evolved in cooperation with microbial DNA. This fact is more important than the interactions that cause diseases created by invading bacteria and viruses.

The organelles in our cells that provide energy like a battery, called mitochondria, were once bacteria inhabiting our cells and were adapted for use by them. Mitochondria actually have their own genomes inherited from the mother without change.

Some of the most archaic micro-organisms on Earth survive today in our microbiome. The microbiome has a major impact on every person's state of disease and wellness.

A poor microbiome seems to be implicated in a wide range of disorders. Some of these, such as chronic obesity and various gastrointestinal disorders, seem to be directly connected to the micro-organisms in the gut. But other connections are not so self-evident, such as how the microbiome may affect autoimmune disorders, asthma, eczema, type 1 diabetes, certain cancers, and even depression and anxiety.

The first stage of exploring this connection involves DNA sequencing of the microbiome, identifying the population of micro-organisms, and studying their chemical output in relation to health and disease. Research is flourishing at this stage, thanks to quicker and cheaper genome typing.

The second stage is to understand the differences in the microbiome that are associated with each disease and conversely, to identify what makes for an optimal healthy microbiome. Rapid progress is being made in determining which microbes contribute to obesity. Some researchers feel that modern diets, polluted air and water, and environmental chemicals have distorted the microbiomes of many populations around the world.

The third stage consists of treatments, both on the disease side and the side of well-being. Probiotics--supplements that improve the state of a person's microbiome--open up a huge area of potential benefits, from increased immunity to disease to slowing down or reversing the ageing process. Another growing area involves fecal micro-biota transplantation (or stool transplant), in which fecal bacteria from a healthy individual are transplanted into an infirm recipient. This has been used, for example, on patients with severe gastrointestinal infections that are resistant to antibiotics, e.g. C. difficile. This technique is also being tried on ulcerative colitis.

 According to some experts, Fecal Micro-biota Transplantation (FMT) works very quickly. For the most part patients start to feel better within the next 24 hours after the procedure.

FMTs are some of the earliest ways medicine is employing a growing understanding of what's known as the microbiome.

Some of the experts compare it with ripping out a weed-infested lawn and laying down fresh turf, is to have a faecal or stool transplant from someone with a healthy microbiome. This procedure has proven remarkably successful in curing people who are seriously ill with Clostridium difficile infection and have very abnormal gut microbes. Research is now under way to extend faecal transplants to other disorders.

The fast emerging science of microbiome
It's not just start-ups pursuing the microbiome. Health giant Johnson & Johnson in February established a microbiome institute, which partners with academic researchers and biotech companies working in the space.

"The science around the microbiome is very quickly emerging, but at the same time is demonstrating some very essential links with some specific diseases such as autoimmune diseases, cancer, diabetes," said Dirk Gevers, global head of the project at J&J. "At the same time it's also opening up an entirely new way of looking at drug development."

A better understanding of the root cause of diseases may enable an approach, through the microbiome, to prevent them. He cited the potential to monitor development of the microbiome in newborn babies, "so when you see the microbiome going off track, you actually are in a position then to intercept and change the microbiome to put it back toward a healthy track. Diabetes and allergy are potential targets for that kind of disease interception.

Sue Dillon, J&J's global therapeutic head for immunology, listed conditions from autoimmune diseases including plaque psoriasis and rheumatoid arthritis, to inflammatory bowel diseases like Crohn's and ulcerative colitis, asthma, diabetes and even cancer as potential targets for microbiome therapeutics.

J&J has partnered with companies Vedanta Biosciences and Second Genome, as well as the Icahn School of Medicine at Mount Sinai in New York and others.

Companies are also mining the microbiome for uses beyond therapeutic ones. Cambridge, Massachusetts-based AOBiome is pursuing a consumer route, having developed a live bacterial spray it says can help users cut back on deodorant and soap. The product, AO+ Mist, contains ammonia oxidizing bacteria that the company calls AOBs.

The company has thousands of customers using the product, said Jasmina Aganovic, general manager of consumer products. It was back-ordered for several months after The New York Times magazine featured a story about it on its cover in May 2014.

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