A unit of RM 8048 consists of four vials each from two dietary pools: omnivore and vegetarian.
NIST
The National Institute of Standards and Technology (NIST) has released a human stool reference material that will help scientists accurately measure the gut microbiome. The initiative aims to speed progress in a cutting-edge field of medical research targeting some of humanity's most serious and intractable diseases.
The human gut microbiome is a rich, teeming ecosystem of microorganisms and their byproducts that line the human gastrointestinal tract. Over the last decade, scientists have linked activity in the gut microbiome to obesity, diabetes, mental illness, cancer and other medical conditions. Researchers believe that a new class of drugs targeting the gut microbiome can treat many of these conditions.
NIST's Human Gut Microbiome Reference Material consists of eight frozen vials of exhaustively studied human feces suspended in aqueous solution, along with more than 25 pages of data identifying the key microbes and biomolecules the material contains. Scientists, including those working at biopharmaceutical and biotech companies, can use this material to further their research and develop new drugs that target the microbiome, including new treatments that contain living bacteria. bacteria.
NIST's stool reference material is "the most precisely measured, scientifically analyzed and richly characterized human fecal standard ever produced," said NIST molecular geneticist Scott Jackson. "We hope our reference material will lay the foundation for gut microbiome research to thrive and reach its full potential."
Gut Microbiome Medicine
D. Ellisor/NIST
As unappealing as it may sound, one of the most promising areas of medical and health research involves treatments and medicines derived from human feces.
Two such drugs have been approved by the FDA to treat recurrent C. difficile infection. This bacterial infection, commonly picked up in hospitals, is associated with up to 30,000 deaths in the U.S. every year.
Fecal transplants - literally transplanting stool from one person to another - have also been used to treat recurrent C. difficile infection. This proved so effective, with a success rate of 95%, that researchers are exploring the use of fecal transplants to treat a broad range of other diseases that may involve the gut microbiome, including alcoholic hepatitis, cancer, colitis and many other illnesses.
Feces-derived treatments work by altering the composition and behavior of the gut microbiome to boost health. Many probiotics sold over the counter at pharmacies today make generic health claims, but they aren't FDA-approved or thoroughly vetted for clinical efficacy.
Jackson said the next generation of microbial medicines will be scientifically tested and proved to be efficacious at treating specific diseases. NIST's reference material will help to make this possible.
"We are at the beginning of a new era of live microbial therapies," said Jackson, "This isn't just wishful thinking. It's already happening."
Why a Reference Material Is Needed
Gut microbiome research is a fast-moving, highly competitive field. Scientists consistently report breakthroughs, and companies invest billions to develop new drugs. However, the field is still relatively new, and researchers use a variety of methods to measure the human microbiome. The myriad approaches can, and often do, lead to differing results that cannot be compared in a meaningful way.
"If you give two different laboratories the same stool sample for analysis, you'll likely get strikingly different results," Jackson said.
Scientists recognize that the wide range of approaches creates problems with reproducibility, where they cannot replicate each other's results. Reproducibility is considered vital in science as it enables researchers to validate and build upon each other's experiments.
The NIST fecal RM aims to help standardize research on the gut microbiome. "It will help ensure accuracy, consistency, comparability and reproducibility in the field," Jackson said.
How the Reference Material Can Be Used
NIST produces over 1,000 reference materials, many for the life sciences, including cholesterol, human DNA and human blood serum. Laboratories use them to ensure accuracy, precision and quality control. NIST's cholesterol reference material, for example, helps ensure that doctors and patients can trust the accuracy of their cholesterol test results.
"We are at the beginning of a new era of live microbial therapies. This isn't just wishful thinking. It's already happening." -Scott Jackson, NIST molecular geneticist
Among the possible uses for NIST's stool reference material are:
- Comparing diverse methods and techniques. The reference material can serve as a "gold standard" or benchmark for evaluating the wide array of approaches researchers and companies use to measure and analyze human feces. The results of these approaches can be compared to NIST's results and to each other to determine which is best suited to achieving specific objectives.
- Enabling reproducibility. If two different labs get similar findings using NIST's reference material, they know that their methods and techniques produce results that can be meaningfully compared.
How the Reference Material Was Made
To obtain fecal material, NIST contracted with a medical services company that recruited individuals and collected stool samples from them. The individuals were all healthy adults, including both men and women. Roughly half were vegetarians and half were omnivores. Because diet affects the composition of the gut microbiome, using these two cohorts ensured that the RM captured a broad range of variability. NIST has no information on the individual donors.
Analyzing the material was a challenge. Fecal matter contains trillions of microorganisms from hundreds of different species, food particles, human cells, and countless proteins, enzymes and metabolites. It is considered one of the most complex biological materials on the planet.
Over a dozen scientists worked for six years to turn those samples into NIST's microbiome reference material. They identified more than 150 metabolites using advanced chemical analysis techniques and more than 150 species of microbes based on their genetic signatures.
They also ensured that the reference material is stable - it's designed to have a shelf life of at least five years - and homogeneous - every sample is the same, within the bounds of stated uncertainties in the measurements.
"Through a lot of trial and error, brainstorming and collaboration with the scientific community, we were able to create a reference material that fulfills the needs of our stakeholders," Jackson said.
The reference material includes eight 100-milligram tubes - four from the vegetarian cohort and four from the omnivores - along with a wealth of information about the microbes and metabolites that NIST identified. The NIST team focused special attention on those compounds and organisms thought to be most relevant to human health and new medical treatments.
"The release of our reference material is a significant step forward," said Jackson. "We're moving toward a time when we can all agree on exactly what we're talking about when we're discussing the human gut microbiome."
