VIDEO: Massive metagenomic database looking beyond microbiome diversity

Tim Spector, co-founder of the UK and US-based company provided a presentation at Probiota earlier this month, discussing how the team has collated vast amounts of customer data which has underlined the importance of the microbiome on metabolic outcomes and shifted the focus from general diversity, to precise bacterial targets.

Spector discussed how the company has accumulated data from hundreds of thousands of individuals, thanks to their at-home test kits which collate individual blood glucose, lipid, and microbiota data in response to identical foods.

He highlights how this has enabled for data analysis to identify specific “good” bacterial species, such as E. eligens​ and B. animalis​. Such strains were linked to better health outcomes, including improved blood sugar and fat control, as well as lower risks of cardiovascular disease (CVD) and type 2 diabetes. “Bad” strains were identified to show contrasting effects, including species such as E. lenta​, C. leptum​, and E. coli​.

“It’s only when you start studying in the tens and hundreds of thousands, the real gene variants come out,” ​he explains.

“This allows us to then reclassify what we call a ‘healthy gut’. Diversity has been very good up until now, but we have found these measures perform better. This means we have started to be able to personalise the microbiome, based on advice that can change this good to bad ratio.” ​

A shift from genetics​

With a background in genetic epidemiology, Spector draws attention to a “pivotal study” which led to the shift in focus from genetics, to the microbiome, in explaining individual variations in response to food. Also known as Predict I, the study​ involved administering 1,000 healthy individuals with identical meals at set times to understand the influence of genetics in response to food.

“We measured everything we possible could for two weeks. The big takeaway was that there was at least a ten-fold variation in how individuals responded to an identical breakfast muffin, whether it was their fat or sugar response. This was also reflected in inflammation levels. ​

“We included 600 twins in our data hoping we would find a genetic effect... we did not. Even identical twins had very different responses to food. So this was quite a big moment,” ​he emphasises.

He described how this led to the founding of Zoe, with its current success mirrored in 2,000 people testing per week, with a further 300,000 on the waiting list. Following the initial tests providing metabolic health scores, the app provides a virtual nutritionist as well as a personalised meal scoring system from 0-100.

“You have to keep your score up to reduce the sugar and fat peaks and nourish your microbiome. It’s a holistic score, suggesting what else can you add to your diet to improve your score. It’s a sustainable method that will work for years. We never measure calories, so you can take back control of your health and weight, based on your own unique body and gut.”​

The company are currently conducting their ‘Predict 3’ study based on this vast nutritional dataset, with a central focus on the microbiome’s links to diet and metabolic health, including hundreds of thousands of participants.

“These are people paying for the product, so it doesn’t cost us anything to do the studies. From this, we are building the world’s biggest metagenome diet and health database,” ​he adds, whilst hinting at additional soon-to-be published RCTs and longitudinal studies on the data.

Microbiome personalisation​

“On this journey, we wanted to look at the genetic contribution to the microbiome, how unique are we. We share 99.5% of our DNA, I’ve always been interested in the differences. But they’re quite subtle when you compare them to the microbiome - we really only share 20-30% of our gut species,”​ he explains.

This observed personalisation of the gut led to a further study​ into the field of menopause, whereby an association was observed with postprandial metabolism and lifestyle, with diet and microbial differences found to mediate the unfavourable symptoms of visceral fat and inflammation.

He predicted the industry will see future menopause innovations coming out as a result.

“We will see some menopausal products coming out of that as we identify particular microbes, and perhaps some active hormones​.”

Future study​

The Zoe scientists are currently looking into the impact of intermittent fasting on the microbiome, and health parameters.

“We are doing the world’s largest study on intermittent fasting, with 140,000 people who are doing it for at least two ​weeks and reporting their mood and energy levels. We can then start personalising lifestyle habits.”​

In addition, he hints to the team’s unpublished study which has profiled over 400 bacterial species; double that of the original Predict 1 study: “With hundreds of thousands, to millions of people – we can now pick up more specific microbes.​

“For example, the prevalence of Blastocystis in different BMI categories. It’s a parasite. I think about 90% of doctors would give you an anti-parasitic drug to remove this. But they’d be wrong. All our ancestors had Blastocystis. But now in the UK, only 24% have it. It’s a marker of being skinny – if you don’t have it, you’re much more likely to be overweight,” ​he explains.