U.S. Department of Energy

Pacific Northwest National Laboratory

At PNNL, a 'Marvelous Year' for Microbiome Science

Four new health-related grants strengthen an already firm Lab foothold on “a new wave” of microbiome science.

Mammalian milk, a flavonoid in hops, xenometabolism, and polyphenols in fecal matter. Four subjects, surely, that are not normally linked. However, all four are tied to one recent bit of news: In the past month, PNNL researchers have been awarded four health-research grants related to the microbiome. (And more are on the way, some of them say.)

Leading roles were played by Janet Jansson, Aaron Wright, and Tom Metz—who said, “Our cup runneth over.”

Most of the projects run for the next five years and are funded through the National Institutes of Health (NIH). Most involve efforts by a dozen or more other scientists at PNNL. And all require the unique analytical capabilities of the Environmental Molecular Sciences Laboratory (EMSL), a U.S. Department of Energy (DOE) user facility located on the PNNL campus.

All of the new grants call out PNNL’s capabilities regarding the interactivity of microbiomes and the environment—missions of interest to both the NIH and to DOE’s Biological and Environmental Research program.

“We are working in living systems that we care about,” and whose functional mechanisms merit investigation, said Wright. His team develops chemical probes that selectively interrogate only functionally active enzymes and cells thought to impact health and disease states.

Wright is principal investigator on a project that will use chemical probes to explain how the gut microbiome is related to the metabolism of drugs and environmental contaminants, both of which are xenobiotic. Anything xenobiotic, for good or ill, is created outside the living system it enters by way of the gut, lungs, or skin. In turn, these outside substances trigger xenometabolism, a variant of normal metabolism, which converts food to energy.

“We’ll make a series of probes so we can directly characterize the (xenobiotic) metabolism process in the gut,” said Wright. “This could apply to exposures that can harm us as well as drugs that can help us.”

The new NIH project will be the first in “the probe realm” for microbiome research, he said, and had its origins in funding from Jansson’s Microbiomes in Transition (MinT) initiative. Based on preliminary data from that, three papers are currently in review.

The MinT funding used activity-based probes to look into glucuronidases, one of five key xenobiotic metabolizing enzyme families. The new grant will fund investigations of the other four. Wright called the grant part of “the new wave” of research emerging out of MinT funding, “and I think it will continue.”

The Promise of XN

Wright, Metz, and Jansson are part of a research grant led by Oregon State University related to a promising natural therapy for inflammatory bowel disease (IBD). One effect of IBD is microbial dysbiosis. Funding comes from the National Center for Complementary and Integrative Health. It is the alternative-medicine wing of the NIH, which funds 27 institutes and centers.

Xanthohumol (XN), the promising natural compound, is a prenylflavonoid abundant in the flowers of the hop plant. Hops gives beer its bitterness and aroma. Now its flowers could relieve IBD.

“We see a trait that is beneficial,” said Wright, “but we don’t know how it interacts with the gut microbiome. We’ll make a probe out of it to see what microns, proteins, and compounds interact. The probe might point to the therapy.”

Metz will use EMSL resources to help researchers at Oregon State analyze their omics data. Researchers there and at PNNL are looking for the fecal and plasma markers of IBD, as well as developing a series of molecular profiles—of XN metabolites, the gut microbiome, the lipidome, and of the fecal and plasma metabolome.

The Microbiome and Milk

Metz and Jansson are paired in a joint grant with the University of Idaho looking at the function of microbial communities found in both human breast milk and in the milk of cows. The grant’s target is mastitis, a painful condition that may be addressed by understanding more about the rich microbial communities in both milk and mammary glands.

Metz and his team will create models and do analyses of lipids and metabolites in breastmilk. They will also assist Idaho researchers in analyzing and interpreting microbiome data. PNNL will use conventional analysis techniques, but add in machine learning too. This branch of artificial intelligence automates the process of building analytical models—a statistical strategy that is used “to pull out the most discriminative data,” said Metz. “You get a big picture of the data when you do that. It’s a good way of finding a biomarker panel.”

Jansson’s role will oversee the microbiome analyses done at PNNL.

The NIH funding is part of a dual-purpose grant—that is, one that is relevant to the human health concerns of NIH and the farm-related concerns of the U.S. Department of Agriculture. Among cows, mastitis costs the dairy industry around $2 billion a year in lost revenue. It is also a serious challenge to animal welfare.

A Tale of Cranberry Extract

Metz is a principal investigator and PNNL project manager on the milk and hops research grants. He also recently won a two-phase grant on fecal microbiome research for the U.S. Army Natick Soldier Research, Development and Engineering Center. PNNL will analyze fecal samples in search of metabolites related to polyphenols (plant-based micronutrients) from cranberry extract.

At least one more health-related microbiome grant is in the wings, said Wright. He agrees with Metz that 2018 has brought a bonanza of microbiome work to PNNL, which has deep capabilities in that multidisciplinary arena.

“This year has been particularly marvelous,” said Wright.

October 2018
| Pacific Northwest National Laboratory