NEWSFOCUS - Human Food...

3
www.sciencemag.org SCIENCE VOL 343 17 JANUARY 2014 241 CREDIT: COURTESY OF JEFF LEACH NEWSFOCUS MANG’OLA, TANZANIA—Jeff Leach hasn’t showered in a month. Living in a small dome tent close to Lake Eyasi in northern Tanza- nia, he stopped washing one day because he wants to know how that will change the microbial populations in and on his body. Leach is taking daily samples of his own stool and skin, which he carefully stores in a liquid nitrogen tank until they can be shipped to the United States. Later this month, the 46-year-old graduate student at the London School of Hygiene & Tropical Medicine (LSHTM) will also adopt the lifestyle of the local people here. He will sleep in their open grass huts, eat their food, and share their tools, to see if his gut flora become more like theirs. Leach, who obtained a Ph.D. in anthropology in 2005, is studying the Hadza, one of the last true African hunter-gatherer communities, because he thinks their gut microbes may hold clues to improving human health worldwide. The Hadza’s lifestyle is thought to resemble that of early humans; they also seem to suffer far less from “modern” diseases, such as diabetes, cancer, and cardiovascular problems. Leach believes there is a connection. An increasing body of evidence has shown that gut microbes regulate their hosts’ immune systems and assist them by eliminating dangerous bacteria, and several studies have linked changes in microbial populations to specific illnesses. The Hadza’s close contact with the vast diversity of microbes in soil, water, and wild food may somehow help protect them, he says—and he plans to spend two full years living here to sample microbial diversity in the people and their environment. His own experiment in Hadza living, which will last a month, will test whether the microbial ecology of a Texan apartment dweller can shift to that of an African hunter-gatherer. Some scientists are skeptical of the premise. They don’t believe our ancestors had such healthy lifestyles or that modern- day Hadza are models of health—and even if they are, their gut microbes may have little to do with it. But many agree that the Hadza project will offer new insights into the complex relationship between humans and their microbiota and that Leach’s roots in anthropology make him the right man for this study. “With his unique background and perspective, Jeff sheds light on questions that I have been thinking of, but haven’t had an avenue to pursue,” says Justin Sonnenburg of Stanford University in Palo Alto, California, one of many microbiologists who will study his samples. Sterile environment Leach’s motivation is highly personal. Eleven years ago, at age 2, his daughter was diag- nosed with type 1 diabetes. After digging through the literature and contacting lead- ing scientists, Leach came to the conclusion that, in addition to a genetic predisposition, a lack of contact with bacteria caused her dis- ease. Leach’s daughter was delivered through a cesarean section, which prevented her from being exposed to the maternal bacteria that most babies encounter in the birth canal. She was breast-fed for a few months instead of the 2 years or more seen in traditional societies, and grew up in a rather sterile suburban U.S. home dominated by antimicrobial soaps and chlorine-wiped tables. This led to an imbalance in her gut microbiota, Leach says, which caused the gut to become inflamed and leaky; that allowed bacterial products to enter the bloodstream and inflame insulin-producing cells in the pancreas, which were then attacked and Online sciencemag.org Podcast with author Jop de Vrieze and slideshow (http://scim.ag/ med_6168). Gut Instinct Do bacteria in the guts of African hunter-gatherers hold the key to a healthier life? An American anthropologist plans to find out Published by AAAS

Transcript of NEWSFOCUS - Human Food...

www.sciencemag.org SCIENCE VOL 343 17 JANUARY 2014 241

CR

ED

IT: C

OU

RT

ESY

OF

JE

FF

LE

AC

HNEWSFOCUS

MANG’OLA, TANZANIA—Jeff Leach hasn’t

showered in a month. Living in a small dome

tent close to Lake Eyasi in northern Tanza-

nia, he stopped washing one day because

he wants to know how that will change the

microbial populations in and on his body.

Leach is taking daily samples of his own

stool and skin, which he carefully stores in a

liquid nitrogen tank until they can be shipped

to the United States.

Later this month, the 46-year-old graduate

student at the London School of Hygiene &

Tropical Medicine (LSHTM) will also adopt

the lifestyle of the local people here. He will

sleep in their open grass huts, eat their food,

and share their tools, to see if his gut fl ora

become more like theirs.

Leach, who obtained a Ph.D. in

anthropology in 2005, is studying the Hadza,

one of the last true African hunter-gatherer

communities, because he thinks their gut

microbes may hold clues to improving

human health worldwide. The Hadza’s

lifestyle is thought to resemble that of early

humans; they also seem to suffer far less

from “modern” diseases, such as diabetes,

cancer, and cardiovascular problems.

Leach believes there is a connection. An

increasing body of evidence has shown that

gut microbes regulate their hosts’ immune

systems and assist them by eliminating

dangerous bacteria, and several studies have

linked changes in microbial populations to

specifi c illnesses. The Hadza’s close contact

with the vast diversity of microbes in soil,

water, and wild food may somehow help

protect them, he says—and he plans to

spend two full years living here to sample

microbial diversity in the people and their

environment. His own experiment in Hadza

living, which will last a month, will test

whether the microbial ecology of a Texan

apartment dweller can shift to that of an

African hunter-gatherer.

Some scientists are skeptical of the

premise. They don’t believe our ancestors

had such healthy lifestyles or that modern-

day Hadza are models of health—and even

if they are, their gut microbes may have

little to do with it. But many agree that the

Hadza project will offer new insights into

the complex relationship between humans

and their microbiota and that Leach’s roots in

anthropology make

him the right man for

this study. “With his

unique background

and perspective,

Jeff sheds light on

questions that I have

been thinking of, but

haven’t had an avenue to pursue,” says Justin

Sonnenburg of Stanford University in Palo

Alto, California, one of many microbiologists

who will study his samples.

Sterile environment

Leach’s motivation is highly personal. Eleven

years ago, at age 2, his daughter was diag-

nosed with type 1 diabetes. After digging

through the literature and contacting lead-

ing scientists, Leach came to the conclusion

that, in addition to a genetic predisposition, a

lack of contact with bacteria caused her dis-

ease. Leach’s daughter was delivered through

a cesarean section, which prevented her from

being exposed to the maternal bacteria that

most babies encounter in the birth canal. She

was breast-fed for a few months instead of the

2 years or more seen in traditional societies,

and grew up in a rather sterile suburban U.S.

home dominated by antimicrobial soaps and

chlorine-wiped tables.

This led to an imbalance in her gut

microbiota, Leach says, which caused the gut

to become infl amed and leaky; that allowed

bacterial products to enter the bloodstream

and inflame insulin-producing cells in the

pancreas, which were then attacked and

Onlinesciencemag.org

Podcast with author

Jop de Vrieze and

slideshow (http://scim.ag/

med_6168).

Gut Instinct

Do bacteria in the guts of African hunter-gatherers hold the key

to a healthier life? An American anthropologist plans to fi nd out

Published by AAAS

17 JANUARY 2014 VOL 343 SCIENCE www.sciencemag.org 242

CR

ED

ITS: JE

FF

LE

AC

H

NEWSFOCUS

destroyed by immune cells. (Several recent studies support this hypothesis.) “Realizing there was a causal relationship between my daughter’s health and the environment my ex-wife and I had created made me feel guilty and angry,” he says.

It motivated him to drop his studies of ancient cooking techniques and focus on a crucial question: How can we rebalance our microbiota to improve health? In 2011, Leach enrolled at LSHTM to obtain a master’s and a Ph.D. in microbiology; a year later, he co-founded the American Gut project, which maps the gut microbiota of thousands of people in the United States.

His Tanzania study is the fi rst to compare lifestyle and microbiota in pure hunter-gatherers with those of Westerners. Previous studies have looked at rural and traditional people in Burkina Faso and Malawi and at several Amerindian communities, but the subjects all practiced agriculture or ate farm products. The Hadza don’t have cattle and don’t grow crops; their diet varies seasonally and consists of fresh game, baobab fruits, berries, tubers, and honey.

On a sweltering day in late October, Leach drives his Land Cruiser through arid terrain dominated by baobab, acacia trees, and small bushes, on his way to a settlement called Kipamba. The day before, he had provided about 40 villagers with plastic tubes and, with the help of his local translator, instructed them how to collect about a tablespoon of their stool in the morning. At our arrival, a young English-speaking boy leads us to a place close to the village where the subjects have gathered.

Leach sets up a table and three chairs, a scale, and a measuring stick. One by one, the men, women, and children hand in their tubes. Leach swabs their right hand for a skin sample, and two local assistants fi ll out a short diet questionnaire for each subject and measure basic body characteristics such as height and weight. Then Leach takes a series of samples from the environment: drinking water, tubers, animal stool, honeycombs, and fresh meat.

On our arrival, the boy had warned us not

to go into the village. “A group of men has been drinking since dawn,” he said. The warning reflects a reality in the 21st century Hadza community: Not all its members are exclusive hunter-gatherers anymore. Some 200 Hadza—mostly those living higher up in the hills—practice the “pure” lifestyle most consistently, Leach says. The 900 or so people living closer to the nearest town, Mang’ola, are leading more Western lives; many have cell phones and regularly consume maize and alcohol. Sodas and snacks are for sale in town.

Leach sees this as an opportunity rather than a problem. By sampling subgroups, he hopes to see refl ections of the transitions our ancestors went through, from hunter-gatherer communities to basic agriculture and small-scale farming, and eventually to high-sugar, high-fat Western diets and life in a built environment. The Hadza, who have been studied extensively by Western scientists for more than a century, are happy to help Leach, whom they call Dr. Mavi, which is Swahili for Dr. Shit.

Like other scientists before him, Leach is aware that he’s bringing change to the very lifestyle he’s studying. The Hadza seek benefits from their participation, such as knives, clothes, and, increasingly, money. Leach refuses to pay them directly but makes contributions to community funds for emergency care and education.

That night, as he sits by a fi re at his camp and sips cheap scotch from a coffee mug, Leach talks incessantly about the Hadza’s eating habits. Their average daily fi ber intake is 75 to 100 grams, seven times the U.S.

average, mostly from pulp and seeds of baobab fruits. Gut microbes turn these

fibers into short-chain fatty acids that nurture intestinal cells and increase the acidity of the colon, he says, which has been shown to thwart opportunistic pathogens. He describes how the Hadza occasionally gorge on meat from a fresh kill, and the huge amounts of honey they eat when it’s plentiful during the wet months of February, March, and April. “From a registered nutritionist perspective, the diet makes no sense,” Leach says. “Yet it does not seem to harm them at all.”

Dying from other causes

Underlying Leach’s research is the assumption that, in their lifestyle and diet, these modern-day hunter-gatherers are as close to humani-

ty’s ancestors as we can hope to get and that they may be healthier because of the way they live. Modern-day humans, in this view, have strayed far from these ancient eating habits and microbes, and our bodies haven’t had the time to adapt.

Not everyone accepts this picture. Humans haven’t stopped evolving since they took up agriculture and settled down some 9000 years ago, says evolutionary biologist Marlene Zuk, the author of the 2013 book Paleofantasy,

a sharp attack on the idea that we should emulate our forefathers. European farmers, for instance, evolved lactose tolerance, enabling them to digest cow milk.

Yale University anthropologist Brian Wood,

who has studied Hadza health and demography,

is also skeptical that the Hadza enjoy rude

health. “It seems like they have less cancer and cardiovascular disease than we do, but we do not have good data to evaluate the actual incidence,” he says. In any case, he notes, accidents, malaria, tuberculosis, and other diseases limit the Hadza’s life expectancy at birth to only 34 years, too short for cancer and heart disease to be signifi cant killers. If the Hadza really are healthier than, say, the

Sweet tooth. The Hadza, a hunter-gatherer commu-

nity in northern Tanzania, often gorge on honey in

the wet season.

Ready to ship. Leach collects

fecal samples from the Hadza and

has them studied at U.S. labs.

AFRICALake Victoria

Lake Eyasi

Hadza area

Dodoma

Mang'ola

T A N Z A N I A

Published by AAAS

www.sciencemag.org SCIENCE VOL 343 17 JANUARY 2014 243

NEWSFOCUSC

RE

DIT

S: JE

FF

LE

AC

H

average German or American, Wood says there’s an explanation that has little to do with microbes: His own research has shown that they eat far fewer calories and are much leaner than Westerners.

As a result, says anthropologist Herman Pontzer of the City University of New York’s Hunter College, the Hadza lifestyle can’t be translated into health recommendations. Leach agrees, but says the research can still tell us a lot about the interaction between humans and microbes before the modern era. “We do not regard the Hadza as a disease-free society,” he says. What he’s most interested in, he says, is “their microbes, their origin, and their interaction with the body. How do these people assemble their microbiota?”

The real payoff of Leach’s research, Pontzer says, could be to show how ancient habits affected the microbiome. “Seasonality in diet and lifestyle is a universal thing that modern societies dropped,” Pontzer says. “The high fi ber consumption is likely to have been universal, too. The same for the intimate relationship with environmental microbes.”

Dream team

The next day, during a visit to another Hadza community, Leach points at a man who is sharpening his arrows for a hunt. “He’s the perfect guy for our study,” he says. “Born vaginally, breast-fed for 2.5 years, has not had malaria or any Western medication, has never

been to town. His shit will probably end up in a germ-free mouse.”

Leach is referring to the fate of his samples: Sonnenburg and his colleagues will infuse stool from Hadza people into the guts of mice that have been born in a sterile environment, allowing the researchers to test the effects of specifi c microbial communities. They will compare the animals’ physiology and metabolism with those of mice colonized by the microbes in Western poop.

Leach says he’s “not a lab rat”; he relies on what Sonnenburg calls a “dream team” of collaborators to carry out most of the analyses. Labs in Colorado and Chicago will do basic taxonomical and functional analyses. Rob Knight at the University of Colorado, Boulder, and Jose Clemente of Mount Sinai Hospital in New York City will compare the Hadza data with American groups, including people following paleo diets, also known as “caveman diets.” Other researchers will use germ-free mice to test the hypothesis that gut microbes help Hadza women, normally quite skinny, put on fat during pregnancy.

The comparison between pure hunter-gatherers and more westernized Hadza will be done by Maria Dominguez-Bello of New York University in New York City, who also wants to compare the Hadza with Amerindians in

South America, who have a far more diverse gut fl ora than U.S. residents. Traditional Africans should have the highest microbial diversity of all, she says, because other populations probably lost species as they went through evolutionary bottlenecks. “I am interested in the disappearance of these microbes,” she says. “Have we lost functions?”

Scientists think that people in modern societies have so little exposure to microbes in the environment that their diets largely determine the composition of their gut microbiota. But in the Hadza, exposure to a daily microbial bombardment from the environment may override any impact of the food, Leach hypothesizes—and he hopes to test that. “Hadza men eat more meat and less plant foods than women,” he says. “If their microbiota turn out to be similar, the environment is the great equalizer.”

Just how intense that exposure can be becomes clear the next day, when Leach receives news that Hadza hunters have killed

a huge female kudu, a great antelope, with their poison arrows. One of the men slits the animal’s throat. Then they cut open its belly, blood spilling everywhere. The men take out the stomach and intestines and hang them in a nearby tree. They cut out the ribs and chew on the raw fl esh. Leach starts taking swabs of the men’s hands and their prey.

Next, the men take the stomach, cut it open, and start rubbing its content all over their arms to wash off the sticky blood. As they do so, Leach explains, the hunters are transferring billions of bacteria to their skin. They cut the stomach in pieces and eat it; then they squeeze the green, fi brous content from the intestines, another rich source of microbes, and eat them, too, still screaming with excitement. The rest of the meat is stripped from the carcass and given to men arriving from other villages.

Tonight, men and women in several Hadza camps will be eating meat. As they hand each other the pieces, they will be passing on many strains of microbes as well—just as they swap bacteria from honeycombs, tubers, berries, and drinking water. This “social network of humans and their microbes,” as he calls it, may be the most important thing missing from Westerners’ disinfected lives, Leach says—and it’s the one thing he failed to provide for his daughter. –JOP DE VRIEZE

Meat and microbes. After killing a kudu, Hadza hunters eat raw meat and rub the content of the ani-mal’s stomach—including billions of bacteria—on their arms.

Published by AAAS