their microbiome investments. But Alex Morgan, a Khosla
Ventures principal with an M.D. and Ph.D. from Stanford,
suggests Khosla’s decision to back Viome has nothing to do
with nutritional advice. Instead, he says, the firm invested
because Viome hired a team of scientists from the U.S. De-
partment of Energy’s Los Alamos National Laboratory. In
addition, Viome had made a deal with the lab to license a
valuable tech platform that has a unique ability to sequence
the biochemical activity in microorganisms.
So even if Jain is selling snake oil, Viome might have sig-
nificant value. Indeed, British pharma giant GlaxoSmith-
Kline struck a royalty deal with Viome in November 2019 to
use its tech to help develop microbiome-derived vaccines.
Jain’s investors could make out handsomely.A
t Caltech in Pasadena, California, mi-
crobiologist Sarkis Mazmanian, 47, is
considered one of the foremost gurus of
microbiome research. In 2012 the MacAr-
thur Foundation gave him a $500,000
“genius” grant for his work on the microbiome’s role in
disease. Since then, he’s been exploring one of the most in-
triguing connections in human health: the “gut-brain axis.”
The working thesis is that the bugs in your belly have a
direct impact on your neurological health, which has pro-
found implications for autism, Parkinson’s and Alzheimer’s.
In 2008, two years after joining the Caltech faculty,
Mazmanian published a cover story in Nature that docu-
mented his successful treatment of inflammatory bowel dis-
ease in mice with human gut bacteria. A Caltech colleague,
Paul Patterson, who was
researching autism in mice,
saw a possible connection to
the digestive problems suf-
fered by as many as 60% of
children with autism.
Together they started test-
ing whether human gut bac-
teria could induce and ame-
liorate autism-like symptoms
in mice. In the midst of their
early work, Patterson was
diagnosed with fatal brain
cancer. In a hospital room
at UCLA where Patterson
was awaiting surgery in May
2014, Mazmanian signed pa-
pers giving Patterson a stake
in a company that would de-
velop drugs from their exper-
iments. “I wanted Paul to get
the recognition of his con-
tribution,” says Mazmanian.
Patterson died the following
month.
Mazmanian is carrying
on their research in his sub-
basement lab at Caltech,where 1,000 germ-free mice, delivered by Caesarean section
in sterile conditions to ensure they are bacteria-free, live
inside plastic-encased rectangular bubbles. Grad students
douse the animals’ food with various gut microbes to test
which bacteria promote tremors and motor problems in
mice that correlate with Parkinson’s symptoms in humans.
In 2016, David Donabedian, a chemistry Ph.D. who was
then a partner at Longwood Fund, a Boston venture capital
firm, volunteered to raise the money and research power to
move Mazmanian’s biotech venture forward. The company,
Waltham, Massachusetts–based Axial Biotherapeutics, has
$55 million in backing and 30 employees. Under Donabe-
dian as CEO, Axial is in the early stages of developing syn-
thetic drugs made of small molecules it hopes will absorb
the particular gut-bacteria byproducts (called “metabo-
lites”) that appear to exacerbate autism symptoms. It’s also
working on a drug to treat the digestive problems suffered
by many people with Parkinson’s.
In the U.S., more than a million people suffer from autism,
and there are no drugs to treat it; an additional million have
Parkinson’s. What would be the value of an FDA-approved
drug for either condition? “I can’t give you a market size,”
says Donabedian. “But if either one hits, it will be huge.”
Chris Howerton, a biotechnology analyst at Jefferies, a
New York investment bank, is less shy. “If every single mi-
crobiome paper turns into a proven therapy, it could im-
pact the drug markets for most major categories of disease,
which together were worth $350 billion in 2018 in the U.S.
alone,” he says. “The breadth of the microbiome’s potential
application is really tantalizing.”MARCH 20 (^20) FORBES.COM
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The Gut-Brain Connection
Caltech professor Sarkis Mazmanian in one of his Pasadena, California, labs. In a trailblazing study,
he transferred gut bacteria from humans with autism into sterile mice who then exhibited autism-like
behaviors. “The most rigorous clinicians and investors,” he says, “realize this is a long journey we’re on.”
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