effective in controlling a C. diff. infection is
a related species called Clostridium scindens.
In a study published last year in Nature,
Buffie and colleagues in the Sloan Kettering
lab of immunologist Eric Pamer, MD, used
C. scindens to defeat C. diff. in mice whose
normal microbiomes had been disrupted
with antibiotics. In the future, Buffie says,
patients with C. diff. might be given pre-
cisely calibrated mixtures of beneficial bac-
teria or drugs that mimic the metabolic
products of C. scindens that seem to prevent
C. diff. from propagating. That would allow
patients to avoid the potential safety risks—
not to mention the ick factor—of a fecal
transplant. Says Buffie: “Being able to isolate,
define, and construct compositions of bacte-
ria that we know have positive effects and
that do not have negative effects—that’s def-
initely an attractive solution.”
This line of research also holds promise
for IBD patients, says Randy Longman,
MD ’07, PhD, an assistant professor of
medicine in gastroenterology and alumnus
of the Tri-Institutional MD-PhD Program
who joined the Jill Roberts Center for
Inflammatory Bowel Disease in 2013.
Preliminary evidence suggests that fecal
transplantation could help those with a
form of IBD called ulcerative colitis, and
Longman and his colleagues are working
to figure out why. “The idea is to be able
to get specific about the microbes,” he
says. “If we isolate some of these bugs
from patient samples and then put them
into gnotobiotic mice we may be able to
understand how these microbes interact
with the immune system within the
intestine.”
Although Longman’s primary occupa-
tion is research, he spends one day a week
in clinical practice, working to help
patients manage their illness. “Inflam-
matory bowel disease, epidemiologically,
affects people in the prime of life,”
Longman notes. “So many of the patients
that I’m seeing for initial diagnoses are
young people with so much of their lives in
front of them. There is a tremendous need
for new medicines and new therapeutic
strategies.” Like his colleagues, Longman is
optimistic that cracking the secrets of the
microbiome will lead to better treatments,
and his patients will one day get relief from
the stress of living with a chronic condi-
tion. “Right now, treating IBD is a manage-
ment thing,” he says. “We don’t cure it right
now. But we do hope for that.”
Today, fecal transplantation remains the best microbiome- based treatment available. But as research points to gut bacteria’s
involvement with a variety of other ailments,
scientists are hoping that future patients
could be helped by targeted probiotics or
drugs modeled after the chemical signaling
of good bacteria. “There may be a point
where it isn’t necessary to cultivate certain
bacteria in your body,” Nathan says, “but
rather to take a pill that provides the
compounds those bacteria are making—to
do the job they do, but in a more orderly,
defined, predictable, consistent, safe way.”
In the future, such treatments might be
used not only for C. diff. and IBD, but
eventually for metabolic disorders, obesity,
and even neurological problems.
“Whether the food you eat influences a
predisposition to atherosclerosis—that’s
controlled by the bacteria in the body,”
Nathan says. “There are influences on
behavior, on weight gain, probably on
asthma. There’s a connection to autism
that’s recently been reported.” The microbiome may have an impact on every
system in the human body, he stresses,
and its importance is inestimable.
Artis echoes Nathan’s enthusiasm, and
notes that most breakthroughs are yet to
come. He draws an analogy to the years
after van Leeuwenhoek’s microscope first
revealed the hidden world in a water
droplet. “The pace of discovery is so rapid;
this field has really exploded,” he says.
“But in terms of understanding the com-plexities of microbiota in the body, we’re
in our infancy.” •
Charlie Buffie, PhD
The knowledge that these bacteria
are present and having no obvious
negative effect on the 5. 5 million daily
subway riders demonstrates that most
of them are neutral to human health, he
adds. They may even be helpful, as they
can out-compete dangerous bacteria.
“The presence of these microbes and the
lack of reported medical cases is truly a
testament to our body’s immune system,”
Mason says, “and our innate ability to
continuously adapt to our environment.”
Would these pathogens be typical for
other cities? With the aim of answering
that question, collaborators are
collecting samples from airports, taxis,
and public parks in fifteen other cities
around the world under a recent grant
from the Sloan Foundation.
The PathoMap project involved
investigators from Weill Cornell, five
additional New York City medical
centers, and more than a dozen
national and international institutions.
Over the course of seventeen months,
medical students and other volunteers
used nylon swabs to collect DNA from
turnstiles, benches, railings, trashcans,
and kiosks in all operating subway
stations across the five boroughs. The
team also collected samples from
inside trains, swabbing seats, doors,
poles, and handrails. They time-stamped each sample and tagged it
using a GPS system, later sequencing
about 1,500 samples (out of more than
4,200 collected) and analyzing those
results. “PathoMap establishes the first
baseline data for an entire city,” Mason
says, “revealing that ‘molecular echoes’
of commuters appear on all surfaces—
from the bacteria on their skin to the
food they eat, and even from the human
DNA left behind, which matched U.S.
Census data.”
The data on New York City’s
ecosystem—an ingredient in building a
smart city—already has potential
real-world applications. Researchers
could monitor the system for changes
that would signal disease or a potential
threat, or someday create a live model
tracking real-time changes to this urban
microbiome. The PathoMap, Mason
says, is just the beginning.
— Anne Machalinski
