SEQUENCING your genome is so 2017. With personalised health becoming a booming industry, several start-ups are now offering to sequence the DNA of all the microbes living in your gut as well.
Emerging research suggests that cultivating a healthy balance of these organisms, collectively known as the gut microbiome, can protect against some of the biggest health threats around, including obesity, diabetes, heart disease, irritable bowel disease, arthritis and depression.
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We might be able to control these organisms with drugs (see “Gut medicine”), but some firms think food is a better option. These companies say they can provide tailored dietary advice to improve your mix of “good” and “bad” gut microbes and optimise your health. However, researchers are saying that the science might not yet be robust enough to help health-conscious consumers.
“It’s a big leap from identifying which microbes are there to knowing how to manipulate them to improve health,” says Amy Loughman at Deakin University in Australia.
The first company to offer gut microbiome sequencing direct to consumers was US firm uBiome, founded in 2012. Firms like Thryve in the US and Atlas Biomed in the UK soon began offering similar services, as did two crowdfunded research projects, American Gut and British Gut.
“A healthy balance of gut microbes can protect against obesity, diabetes and depression”
These early tests used a technique called 16S ribosomal RNA analysis to determine the types of bacteria in customers’ stools and hence in their gut. They could only identify broad categories of microbes, however, because the technology sequences just a small part of the overall bacterial genome.
More recently, a method called shotgun metagenomics has made it possible to drill down further. It sequences the full genomes of many microbes in a stool, letting you identify individual species. In addition to picking out bacteria, it also detects other microbes that may influence gut health, such as fungi, archaea and viruses.
In 2016, Israeli company DayTwo launched the first consumer version of this new metagenomics test, based on research by the Weizmann Institute of Science. uBiome then began offering a similar test in January this year, and Australian company Microba, founded by biologists at the University of Queensland, followed in July.
Each company sells tests for around US$300. They send out home stool collection kits by post, then extract and sequence DNA from customers’ samples, before using metagenomics to decode the thousands of microbial species present.
uBiome gives customers a simple read-out of the microbes detected, along with information about what they do inside your body, such as producing vitamins. DayTwo and Microba go further and provide personalised dietary advice based on the microbes they find.
DayTwo says it can identify foods that will help control blood sugar and thus protect against diabetes, obesity and heart disease. The foods it recommends are different for everyone as they are based on each individual’s mix of gut microbes.
To offer this advice, the firm uses an algorithm developed by Weizmann researchers. In a , they found that people responded differently to identical meals because of their unique gut microbiome. For example, some people had higher blood sugar spikes after eating sushi than after eating ice cream.
Using data from 800 people, the researchers trained a machine-learning algorithm to predict the best blood sugar-lowering diets for each individual based on their set of gut microbes. They then validated it in a follow-up trial of 26 people. “It’s probably the most evidence-based of the tests so far,” says Loughman.
Food for thought
Microba takes a broader approach. It offers dietary advice to boost 17 types of bacteria associated with reduced risks of developing a range of diseases. For example, it measures the levels of Faecalibacterium prausnitzii, which is thought to protect against bowel cancer and inflammatory bowel disease. If customers have below-average levels, the company recommends eating blueberries, watermelon, asparagus, broccoli and other foods containing nutrients that promote the bacteria’s growth.
It is unclear whether this will actually make much difference to your health. “It’s a good start, but there are thousands of other bacteria in our gut as well and we’re only just beginning to understand which ones are important and how they work together,” says Loughman. “In most cases, it won’t be a single species driving one disease.”
Microba hasn’t conducted clinical trials to validate its dietary recommendations yet, but it plans to recruit customers for follow-up studies. “At the moment, the test should mainly be treated like a neat informational tool. We’re not at the point where we can diagnose or treat disease,” says Alena Pribyl, one of the company’s biologists.
Pribyl says Microba’s services do help people by explaining why they should be eating certain foods. “We’re all told to eat more fruit and vegetables, but we don’t know why and so most of us don’t,” she says. “If you know that eating blueberries will promote the exact bacteria that you’re deficient in and potentially protect against disease, that might be more motivating.”
Rob Knight at the University of California, San Diego, says the tests have “tremendous potential”, but advises treading with caution for now. “I don’t think we know enough yet to be able to make personalised dietary recommendations with great confidence,” he says.
Some customers have already questioned the reliability of the tests after getting contrasting results from different services. For example, Tami Lieberman of Harvard University after sending them separate portions of the same stool.
Other customers have reported receiving , for example, a recommendation to drink coffee and red wine from one, and advice to avoid them from another.
These discrepancies most likely come down to the different methods firms use to prepare samples, extract and sequence DNA, and interpret the data, says Knight. He recommends choosing companies with testing protocols that have been validated through research, rather than those with undisclosed proprietary methods.
“We’re all told to eat more fruit and vegetables, but we don’t know why and so most of us don’t”
With increasing interest in microbiome health, there is a risk that some companies will make overinflated promises, says Loughman. We have already seen that happen with genome-sequencing firms, some of which make questionable claims about being able to pick the perfect workout or romantic partner for their customers based on their DNA. “It’s ripe for the same kind of thing because there’s so much money and public interest at the moment in gut health,” she says.
For the time being, Knight says that microbiome sequencing should be viewed as a fun science project rather than a reliable way to enhance your health. “If you’re interested in the process of discovery and finding out more about who you are and what’s inside you, then go for it, but it’s not a way to overcome health problems yet,” he says.
Nevertheless, both Knight and Loughman are optimistic that gut microbiome sequencing will help people improve their health in the future, once we know more about the role of individual microbes, how they work together and how they can be manipulated to prevent or treat disease. “I think this is the start of something that could be extremely powerful,” says Loughman.
Gut medicine
Rather than fine-tuning our gut microbes with food (see main story), we may be able to do it with drugs.
US company Synthetic Biologics, for instance, is developing a microbe-modifying drug to . It stops gut bacteria called Methanobrevibacter smithii from producing excess methane gas, which can cause bloating, constipation and abdominal pain. An early clinical trial found that the drug relieved the symptoms of irritable bowel syndrome, and a larger trial is planned for next year.
French company Enterome is developing a drug to . It stops harmful E. coli bacteria from attaching to the gut wall and triggering inflammation, which is one hallmark of the condition. The drug was shown to be safe in a preliminary clinical trial, and is due to undergo a larger trial this year.
Dairy treatment
Modifying your microbes could also help . A drug being developed by Ritter Pharmaceuticals in the US stimulates Lactobacillus and other bacteria in the large intestine to break down lactose as it passes through. An early study found that the drug allowed people with lactose intolerance to consume dairy products without any abdominal pain, and a large trial is now under way.
These drugs are more sophisticated than probiotics and faecal transplants, which have previously been used to alter the gut microbiome. Probiotics simply introduce “good” bacteria into the gut, while faecal transplants contain a mix of bacteria from healthy donors’ stools.
This article appeared in print under the headline “Meet your microbes”
