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American Gut Archives - Omics Help Desk

How to validate microbiome testing services now that uBiome got busted?

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When science discovers new links between our health, the bacteria in our gut, what we eat, our brain functions, and our moods, people pay attention. Microbiome research has uncovered those gut-brain-axis links after the National Institutes of Health launched a five-year, $150 million research effort, which in turn gave rise to several microbiome testing and research startups who received hundreds of millions in financing, among them Finch TherapeuticsKallyopeSecond Genome, which research specific diseases, and startups such as uBiomeViomeThryve, DayTwo selling direct-to-consumer testing kits for disease prevention. There is also a public, not-for-profit project called American Gut, which has the lowest price for sequencing people’s microbiome at $99 but is limited in its results. Microbiome testing, like all types of genome sequencing or genomics tests, sequences the DNA (or RNA) of living organisms, bacteria and other microbes in this case.

One of these companies, uBiome, will no longer be included in that list. uBiome raised $83 million in venture capital, and was worth a whopping $600 million at the start of 2019, making the deep dive they took recently to nothing more than a liquidation valuation even more dramatic. After a series of unfortunate events of their own making, uBiome got busted for bad accounting practices, and most recently, for faulty science. It has now filed for Chapter 7 with plans to shut down. As reported by FierceBiotech, CVS stores turned down stocking their shelves with uBiome’s at-home, Explorer microbiome consumer test, after the shocking news were revealed. Two weeks ago, Business Insider reported that uBiome lost their laboratory certifications, forcing them to stop their clinical tests activities. Perhaps worse than the accounting practices are the news that the Explorer test had been tainted by using a reference sequence database that included samples from minors, infants and at least one animal and that was populated by fecal samples volunteered by employees and participants from an online fundraiser.

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What’s Up Microbes?

Health

AG-Nephele-side-by-side2There is no doubt that the little bugs that live inside our bodies and on our skin affect our health and well-being, even our state of mind, but what we want to know is, by studying them, can we prevent disease or even just a bad mood? And how can we monitor them on a daily basis? Will there be an app called “What’s up microbes?” that communicates with some new device that checks on those microbes and reports back what we should eat or if we should go see the doctor, or go for a run, or take it easy and relax to ensure we maintain a healthy microbial equilibrium?

A few months ago, I shipped my “gut microbiome” inside a narrow transparent tube via the US postal mail service to American Gut. My microbiome made the long trip from Miami to California stuck on a Q-tip. At the time, it seemed that the scientific research into this tiny new world of microbes had come a long way, but to my disappointment, I found out that there is still much to be learned. I found out that my microbiome had not survived the trip intact and had started to bloom, aka “grow new bacteria” during the trip.

In recent years, the microbiome has been featured prominently in the news as one of several paths to personalized medicine. Researchers from diverse fields such as psychology or nutrition or cancer, and many others, are trying to join the race to decipher it. There is great promise in its research, which is why the sector is receiving billions in funding, with major research initiatives in the US and worldwide. But as of today, the microbiome is still a mystery.

A 2014 article titled “20 Things you Didn’t Know About the Human Gut Microbiome” aptly describes the microbiome this way:

The microbiome is defined as all the bacteria, viruses, fungi, archaea, and eukaryotes that inhabit the human body. Collectively referred to as the “second human genome”, the gut microbiome in particular is now being considered a separate “organ” with distinct metabolic and immune activity. The two major areas of microbiota investigation include taxonomic diversity to identify “who” is there and functional metagenomics to figure out what they are doing. There are other human microbiome sites as well, including skin, oral, and vaginal, but the gut is the most popular and diverse neighborhood.

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What’s New with the Microbiome Quality Control Project?

Health

In 2013 two services, American Gut and µBiome (pronounced you-biome), launched through the crowdfunding website Indiegogo to sequence the human microbiome of anyone interested in doing so. In 2014, an intrepid blogger, decided to donate her used toilet paper to science. What she found out is that the results of the two services were almost complete opposites in regard to the proportion of certain bacteria that can say a lot about diet and health.

She wrote:

It turns out that I’m not the only one to notice problems with the companies’ fecal microbiome analysis. One blogger found differences between the microbes taken from two different parts of the same, uh, sample.

So what could have gone wrong with my microbiome? Perhaps the samples weren’t collected right. According to American Gut’s sampling instructions, too much brown stuff can interfere with the methods the scientists use to break open bacteria and pull out the DNA inside. Too little and they might not get an answer at all. I thought I had used Goldilocks-like precision, and that one — or maybe both — of the sequencing services must be wrong.

Another possibility: corrections to the data may differ between companies. Another blogger, who is a bioinformatician, got different results than American Gut reported to him when he used his own software to analyze the raw data. It turns out that some bacteria grow while in the mail and can take over the sample, so American Gut corrects the reports it sends to participants to account for that overgrowth.

In the end, I thought I’d go right to the experts for the straight poop. I approached Jessica Richman, one of the cofounders of µBiome, and Rob Knight, one of the leaders in the microbiome field. His lab group runs the American Gut project as part of their quest to learn how diet, lifestyle, geography and other variables influence the microbiome.

She mentioned that the Microbiome Quality Control (MBQC) project would bring some consistency to the field and that was in 2014. Almost 1.5 years later, in December 2015, the microbiome quality control project published a paper on “Baseline study design and future directions” reporting on the first MBQC baseline study project and workshop. Clear cut protocols that guarantee trustworthy results are being designed but still not fully implemented:

There was a consensus across the MBQC participating groups that although microbiome measurements face substantial challenges, this baseline project was very successful and represented impressive progress towards the overall goal of establishing practical guidelines for reproducibility within labs over time and across the field.

We expect that for those of us who waited long enough to sequence our microbiome, we will benefit from all the research that was conducted into establishing those quality control guidelines that make microbiome studies reproducible and reliable. That is why I sent my Q-Tips to American Gut last week! Now I am waiting for the results.

 

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