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Microbiome Archives - Omics Help Desk

How does our personality affect our gut microbiome?

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Our personality is formed by our genes, our lifestyle, our life history, and our environment. Now we learn it is perhaps molded by our inside environment, our microbiome, the ecosystem of gut microbes that live inside us and metabolize our food. As reported yesterday in Inverse, Katerina Johnson, a research associate at the University of Oxford, is publishing a study in the March 2020 edition of the Human Microbiome Journal, in which the gut microbiome is investigated with respect to human personality. The study reveals that people with larger social networks tend to have a more diverse microbiome, and as we know, a more diverse microbiome is associated with more optimal health. The study also found, like many other studies before, that anxiety and stress are linked to reduced diversity and an altered microbiome composition.

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Sleep problems? Your microbiome may have some answers!

Health

We have known for a while that the population of bacteria in our gut, our gut microbiome, affects the digestive, metabolic, and immune functions in our bodies, but science is showing that it also regulates our sleep and mental states through the microbiome-gut-brain axis. A scientific review study by Rijo-Ferreira and Takahashi published December 2019, discusses how our sleep and wake cycles, also called circadian rhythms, are affected by our genes, by our metabolism, by time-restricted feeding protocols, and by our microbiome.

An earlier review study by Li et al 2018, listed several gut bacteria that affect sleep. For example, some spore-forming bacteria, primarily from the Clostridium genus, modulate the amount of serotonin in the blood. Serotonin is known to promote REM sleep and low levels of serotonin are linked to the development of depression. In addition, Escherichia coli and Enterococcus, which are common in the intestinal tract, also produce small amounts of serotonin. The bacteria Lactobacillus and Bifidobacterium can secrete the neurotransmitter GABA, and abnormal expression of GABA mRNA is often observed in patients with depression and insomnia.

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The portable MinION sequences a microbiome in 1-5 hours – Can we use it at home?

Health

A study by Leggett et al 2019, published in December, presents results from using the portable  MinION to sequence the microbiome of preterm newborns admitted to the neonatal intensive care unit of a university hospital. The bacterial DNA sequence analysis pipeline developed by the authors of the study obtained a majority of the results (or 70% of reads) after 1 hour with no more differences found after 6 hours. In this short time, the pipeline identified pathogenic bacteria and their corresponding antimicrobial resistance gene profiles, which for patients in the ICU can provide a lifesaving diagnosis when deciding on the right antibiotic.

Some of the remarkable features of the MinION, which is produced by Oxford Nanopore Technologies (ONT) are the small size of the DNA sequencing device, the long read length of the DNA sequences, and the sequencing speed. 1 to 6 hours is very quick compared to current rapid clinical microbiology tests, which include determination of antibiotic susceptibility, and take between 36 and 48 hours. More widely-used and larger DNA sequencers like Illumina MiSeq take between 4 and 55 hours for a run according to the Illumina web site. This new research presents a promising life-saving diagnostic tool in the clinical setting, but one wonders, if it is so small and portable and so quick to sequence DNA, can we use it at home to sequence our own microbiome?

The answer would be yes if we disregard for a moment the “wet lab” hurdles required to operate the MinION. Having a little home DNA sequencer would allow us not only to monitor an infection by sequencing our microbiome early on, when we feel we are coming down with something, but also monitor our overall health and moods now that we have so much evidence of how the gut-brain axis affects our well-being and how our diet, our fitness, and our moods affect our microbiome.

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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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Where is the Beef in a Vegan’s Microbiome Test Results?

Health

Screenshot excerpts showing Miss Vegan’s and Q Bob’s  Viome microbiome test results

A growing list of direct-to-consumer (DTC) microbiome genetic testing services have popped up in recent years since I first tested my own microbiome sample and wrote an article in Omicshelpdesk.com about it. If you are not familiar with the microbiome or with microbiome sequencing you might want to read that article first.  Since then, hundreds of millions of dollars in financing have been invested in microbiome testing startup companies like uBiomeViomeFinch TherapeuticsKallyopeSecond GenomeHuman LongevityMaat PharmaSeed.

Many of these startups are focused on nutrition and making diet recommendations as that is the most obvious application when studying gut bacteria which are in fact responsible for metabolizing the food we eat, and it is also the least risky business one may attempt at this still early stage of microbiome research. They all seem to have very nice reports and user interfaces from the screenshots I looked at. The one service I looked at more attentively this time around is Viome, by accessing the reports that a vegan friend allowed me to see in the Viome web site and app, which contained the results of her microbiome test. In this article I compare her results to those of a man who runs a personal blog called Quantified Bob. In his blog, Q Bob, as I will call him here, shares his experiences quantifying everything that can be measured in his body or about him.

But before presenting that comparison, I would like to bring some attention to two important inquiries we need to pursue before choosing and paying for a DTC microbiome test in order to assess its validity: (1) We should research if the technologies and methods the company uses have been validated; and (2) We should ask if the service offers access to the raw sequence data.

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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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Fitness, Diet, Clinical, Genome, Microbiome Data, it is All Yours

Health

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There are ongoing efforts to merge your health data and have it in a central place. Other efforts involve transferring or exchanging your health data between hospitals and doctors and you look forward to not having to spend 20 minutes filling out the same paper form you filled out at another doctor’s office. Yes, that will happen, eventually. But should this central place that holds your data only serve your doctors or should the information it contains directly guide your life style and life choices? You have read that eventually, a smart computer will access your health data and make a faster, more accurate diagnosis or create a personalized treatment plan. You have read that such a system will make recommendations on your diet, your physical exercise regimen and even your social life and your career (work less, take time off). These recommendations will help you lead a happier, healthier and fuller life. It is already happening today, with apps like Fitbit and MyFitnessPal being pioneers in the field.

Today, doctors, clinics and hospitals have portions of your health data. It is spread across filing cabinets, devices, and the computers owned by these institutions. According to HIPPA regulations you can ask for that data but the data collected at a particular health provider belongs to him or her.  Now consider this: 23andme and similar institutions have your genetic data but they don’t have your doctors’ health data. uBiome has your microbiome data but nothing else. Your Fitbit or similar fitness tracker has your fitness data but they don’t have your genetic data or your medical health history. You have been recording your weight and consumed calories in applications like MyFitnessPal, but nobody but you has that data. Ultimately, you have the right to access and own all that data and share it as you seem fit.

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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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