Take a Deep Breath and Say Hi to Your Exposome


Researchers begin to explore the unique cloud of airborne microbes and chemicals that surrounds each of us

Take a Deep Breath and Say Hi to Your Exposome
Stanford scientist Michael Snyder shows the device that was used to monitor the microbes, chemicals and particulates to which clinical trial participants were exposed as they went about their daily lives. 

In the past few decades, researchers have opened up the extraordinary world of microbes living on and within the human body, linking their influence to everything from rheumatoid arthritis to healthy brain function. Yet we know comparatively little about the rich broth of microbes and chemicals in the air around us, even though we inhale them with every breath.

This struck Stanford University genomics researcher Michael Snyder as a major knowledge gap, as he pursued long-term research that involved using biological markers to understand and predict the development of disease in human test subjects. “The one thing that was missing was their exposure” to microbes and chemicals in the air, Snyder says. “Human health is clearly dependent not just on the genome or the microbiome, but on the environment. And sampling the environment was the big hole.”

In a new study published September 20 in Cell, Snyder and his co-authors describe their efforts to fix that. They aim to do so with a wearable device that monitors an individual’s daily exposure to airborne bacteria, viruses, protozoa, fungi and chemicals—the so-called exposome. Similar studies in the past have largely relied on a few fixed sampling stations; the Stanford researchers instead modified an existing monitoring device, the size of a big kitchen matchbox, to be strapped to a person’s upper arm or kept nearby. The device continually sipped the air around the 15 test subjects at home, at work and on the road, passing the air through separate filters to collect both biological and chemical compounds. DNA sequencing, together with comparisons of the results against a reference genome database of 40,000 species, indicated that the 15 participants had been exposed to 2,560 biological species—more than a thousand of those after wearing the device for just three months.

Mass spectrometry analysis added 3,300 chemical signals to the mix. The researchers were able to identify fewer than a third of them—but they note that all the chemicals had passed through a pore-sized filter for the biological assay and could thus potentially reach deep into a person’s lower respiratory tract. Almost all of these samples contained diethylene glycol, used in products from brake fluid to skin cream. The insect repellant DEET also popped up everywhere, apparently an artifact of sampling mainly during the San Francisco area’s insect-friendly springtime. The study calls this “a previously unrecognized type of potentially hazardous exposure,” noting that no government agency “has evaluated possible health risks associated with inhalation” of such compounds.

Snyder and his co-authors suggest that any given person’s exposome is a product of two separate but interacting “clouds”—a term redolent of the dusty shadow around the character Pig-Pen in the Peanuts cartoon. One cloud is environmental and shared with immediate neighbors; the other is more personal, consisting of human- and pet-centric bacteria, fungi, parasites and protozoa. The test subjects lived scattered across the Bay Area, but the interaction of these two clouds meant that individual exposomes were often strikingly different.

Snyder’s exposome, for instance, showed relatively low exposure to pyridine, apparently because the paint in his house lacks this common antifungal additive. Thus, Snyder also lives with a rich fungal flora as a result. By comparing the timing of a mild allergy with his exposome results, he also discovered that the pollen causing his symptoms came not from the pine trees in his yard, as he had suspected, but from a eucalyptus.

Beyond human health, says the study’s first author Chao Jiang, a postdoctoral researcher in Snyder’s lab, the exposome monitor “is a great tool for studying the evolution and ecology of the things living around us, for exploring the diversity of life.” It can even provide insights into our own hidden emotions. Many of the study’s samples, for instance, contained geosmin—the chemical compound responsible for the earthy smell that causes us to inhale deeply, and often with a hint of joy, when rain comes after a drought. “It’s not just about things that can kill us,” Jiang says.

David Relman, a Stanford microbiologist who was not involved in the study, described the new research as “fascinating for the set of questions it raises, more so than for anything it might answer.” Environmental health studies often cannot explain the puzzling variability in individual health among people living in the same area and exposed to the same pollutants, he says. The conventional explanation is a kind of epidemiological shrug: Maybe some people experienced a different dosage? Maybe they were genetically predisposed to be vulnerable?

Exposome monitoring, on the other hand, “allows for massively parallel collection of data,” Relman says. “And that means we can look for combinations of environmental factors that are present at the same place or time, and that might have synergistic or even antagonistic effects for human health.” Imagine a group of people is exposed to the same toxic chemical, he suggests. It might turn out that severe symptoms occur only in those victims also exposed to a certain fungal spore at the same time, for example, and not in people who do not encounter that particular fungus.

“The technology is great. The ability to collect both microbial and chemical components you are exposed to is brilliant,” adds University of Chicago microbiome researcher Jack Gilbert, who also was not involved in the study. “I want the technology. I want it for my own research.”

But Gilbert adds that “the general design of the study was not ideal,” mainly because he believes there were too few test subjects and too few replications in comparable circumstances. A better design, he suggests, might involve comparing the daily exposomes over a month for 10 or 20 health care workers in the hospital, versus an equal number based at home. Gilbert adds that Snyder “has been very open about the fact that the amount of data in the study design wasn’t perfect,” largely for budgetary reasons.

Each monitoring device cost $2,700 before modification, according to the study, and testing of samples was even more expensive. But Snyder says that his team now hopes to deploy a miniaturized version of the monitor—this one about the size of a small pocket matchbox—on 1,000 test subjects a year from now, with the ultimate goal of commercializing a smartwatch version of the exposome monitor.

Snyder adds that he is currently wearing eight different monitoring devices, including three smartwatches, either to collect data or to evaluate new technologies. The first version of the exposome monitor was “a bit clunky,” he admits. “And as they get older they hum more. My wife notices it. There are times when she says, ‘Do you have to have that thing?’” But he adds, in the course of an interview, that it is on his desk—still monitoring as he speaks.

Stroke Rounds: Novel Clot Buster Flops Again


Desmoteplase didn’t help late-presenting strokes, the DIAS-3 trial shows.

The investigational thrombolytic desmoteplase didn’t improve reperfusion or outcomes compared with placebo in ischemic strokes treated 3 to 9 hours after onset, the DIAS-3 trial showed.

A good functionally independent outcome, marked by a modified Rankin Scale score of 0 to 2, at 90 days occurred in 51% of desmoteplase-treated patients compared with 50% given placebo (P=0.40), Gregory W. Albers, MD, of the Stanford School of Medicine in Stanford, Calif., and colleagues found.

Recanalization at 24 hours, monitored with noninvasive imaging, likewise came out similar between treatment groups (49% and 42%, respectively), they reported in the June issue ofLancet Neurology.

“This factor is key in the neutral results and raises questions about the thrombolytic efficiency of desmoteplase in late time windows,” Michael D. Hill, MD, and Bijoy K. Menon, MD, both of the University of Calgary Stroke Program in Alberta, wrote in an accompanying editorial.

The prior phase III DIAS-2 trial with the drug, which is based on the saliva of the vampire bat, had also turned out negative using a different imaging-based selection scheme for enrollment.

DIAS-3 used a “simpler imaging selection paradigm: small core (less than a third of the middle cerebral artery [MCA] or less than a half of the anterior cerebral artery [ACA] or posterior cerebral artery [PCA] territories), plus evidence of a target intracranial arterial occlusion,” Hill and Menon noted.

However, imaging protocol violations were common in the trial, with imaging discrepancies in 21% of the 292 acute ischemic stroke patients with occlusion or high-grade stenosis in major cerebral arteries treated at a median 7 hours after onset.

Although serious adverse events, including intracerebral hemorrhage and symptomatic cerebral edema, were similar between groups, another phase III trial, DIAS-4, was stopped based on early indications of futility in DIAS-3.

The researchers pointed to a possible benefit of desmoteplase in small ischemic lesions selected by MRI that might be worth further study.

While that group might have been less prone to imaging measurement error, “this finding would have been more meaningful if increased recanalization early after administration of the thrombolytic agent was also shown in the small core group,” the editorialists cautioned.

It may be that late-presenting, small core strokes are just not a good population to target, they suggested.

“We speculate that patients who arrive late without having a large, established core of infarction shown in imaging are more likely to have preserved penumbral tissue because of good intracranial collateral circulation,” Hill and Menon wrote. “Such patients could stand to benefit less from thrombolysis, even with reperfusion.

“Further, with time, thrombi mature and fibrin cross-links, resulting in resistance to thrombolysis. Patients who present in later time windows might simply be less amenable to chemical thrombolysis.”

Alzheimer’s patients to be treated with the blood of under-30s


Alzheimer’s patients in the US will be given transfusions of young people’s blood as part of a promising new treatment that’s nowhere near as crazy as it sounds.

young-blood

Image: alexskopje/Shutterstock

This October, people with mild to moderate levels of Alzheimer’s disease will receive a transfusion of blood plasma from donors aged under 30.

The trial, run by researchers at the Stanford School of Medicine in the US, follows their revolutionary study involving lab mice, where the blood plasma of young mice was injected into old mice, resulting in a marked improvement in their physical endurance and cognitive function.Completed earlier this year, their research, combined with independent studies by a handful of research teams around the world, pin-pointed a plasma-borne protein called growth differentiation factor 11 – or GDF11 – as a key factor in the young blood’s powers of rejuvenation.

“We saw these astounding effects,” lead researcher and professor of neurology at Stanford, Tony Wyss-Coray, told Helen Thomson at New Scientist. “The human blood had beneficial effects on every organ we’ve studied so far.”

Getting approval for their October trial has been fairly straightforward, he said, because blood transfusion therapy has such a long history of safe use in medical procedures, but the team will still keep a very careful eye on how the patients are progressing once they’ve received the young blood. “We will assess cognitive function immediately before and for several days after the transfusion, as well as tracking each person for a few months to see if any of their family or carers report any positive effects,” he told Thomson at New Scientist. “The effects might be transient, but even if it’s just for a day it is a proof of concept that is worth pursuing.”

Without wanting to get ahead of ourselves just yet, if the trial ends up being a raging success and the Stanford team can prove once and for all that young blood reverses the debilitating effects of Alzheimer’s and other degenerative diseases such as cancer, we’re going to need a whole lot more donors to meet demand around the world. Or, as Wyss-Coray told New Scientist, the hope is that continued research will identify the individual components in the plasma that are contributing to the positive effects – such as GDF11 – and get these synthesised into new types of drugs.

“It would be great if we could identify several factors that we could boost in older people,” he said. “Then we might be able to make a drug that does the same thing. We also want to know what organ in the body produces these factors. If we knew that, maybe we could stimulate that tissue in older people.”