The science behind the idea of restoring the intestinal #microbiome to an ancestral state is shaky, skeptics say, and in some cases unethical.
As the sun set in Tanzania on a September evening in 2014, Jeff Leach inserted a turkey baster filled with another man’s feces into his rectum and squeezed the bulb. The feces, he said, came from a hunter-gatherer who was a member of the Hadza people and lived nearby.
Mr. Leach said he was trying to “rewild” his microbiome, giving himself microbes that can protect against chronic and autoimmune diseases that plague people in Western societies — including obesity, diabetes and irritable bowel syndrome. The theory relies on the idea that people like the Hadza have diets and lifestyles that are more like those of ancient populations, and harbor such microbes. Channeling tropes that could have come from colonial era literature, Mr. Leach said the man he got the feces from “had only recently dined on zebra and monkey.”
Rewilding the microbiome is now a rising area of study — combining microbiology, epidemiology and anthropology — with big money at stake. Finch Therapeutics, a microbiome start-up founded by scientists at M.I.T., recently raised $128 million in an I.P.O., even though it has no product on the market.
But “rewilding” is hotly debated, both as a medical and ethical enterprise. Critics ask basic questions about the validity of the science itself: How do you know what microbes people had in their guts before industrialization, and why do you think people were healthier then? If you decide to add some back, why would they succeed in a colon already teeming with trillions of microbes all fighting for a niche?
The movement has gone too far on minimal evidence, said Rachel Carmody, an evolutionary biologist at Harvard and the lead author of a recent paper in Science outlining rewilding’s weaknesses.
“We wanted to put the brakes on,” she said.
The ethical questions sit uncomfortably close to science’s history of racism and exploitation. Experts question why the Hadza are being treated as proxies for Paleolithic people. What did these hunter-gatherers actually agree to when they provided fecal samples in return for small gifts? And what will happen if their bacteria turn out to be commercially valuable?
Mr. Leach makes this volatile debate even more complicated. Several women have accused him of sexual assault and researchers he has published papers with are distancing themselves from him — although they have not stopped using his samples from the Hadza.
Yet the microbiome rewilding movement did not come from nowhere. The question is, how did it grow so big and, if the idea is valid, how can the science be separated from what one researcher, in an interview, called a “colonial endeavor”?
The Start of a Movement
The idea of rewilding took off after a remarkable experiment’s results were published in 2013. Dr. Jeffrey Gordon, a microbiome researcher at Washington University in St. Louis, and his colleagues obtained fecal samples from pairs of identical twins in which one twin had obesity and the other did not.
They transferred those feces to mice. The mice that got feces from the twin with obesity grew fat. The others did not.
After that, fecal transplants quickly became “the tool in the microbiome field,” said Aleksandar D. Kostic, a microbiome researcher at Harvard.
Transplants are also used routinely to treat people whose colons are overrun by antibiotic resistant C. difficile, a bacterium causing relentless diarrhea. And they are being studied as a treatment for inflammatory bowel disease and Type 1 diabetes, as well as a treatment that enables cancer patients to respond to checkpoint therapy, a type of immunotherapy.
Others are trying bacterial supplementation on their own, with no assurance that it works.
“What many of us do, including me, is take probiotics,” said Dr. Kostic, who also co-founded a probiotic company, Fitbiomics. These are commercial products made up of harmless bacteria whose benefits have not been proved.
Dr. Kostic is hoping for digestive benefits from probiotics, but added that “people have made all sorts of other connections as far-ranging as sleep patterns and even mood to some extent.”
Enthusiasm for altering the microbiome led naturally to the rewilding movement. Rewilding could answer the question: If you are going to try to remake the microbiome, what are the best microbes to remake it with?
In 2017, in a paper Science promoted on its cover, Justin Sonnenburg, Mr. Leach and others compared microbes in the guts of 18 populations in 16 countries. Their study showed a clear distinction between the microbes in people living in industrialized societies and those living in what the investigators called “more traditional” societies, with a particular focus on the Hadza in Tanzania.
“That really clearly shows there are some families of bacteria that are super abundant in all these traditional populations around the world that are rare or extinct in Western populations,” said Dr. Sonnenburg, an immunologist and microbiologist at Stanford University. “That said to us: There were microbes that have lived in humans for hundreds of thousands or probably millions of years, even before modern humans arose, but as populations industrialized we lost those microbes.”
In a 2018 paper in Cell, Dr. Martin Blaser, a professor of the human microbiome at Rutgers, made the case for rewilding: Because of widespread antibiotic use and diets laden with processed foods and lacking fiber, the human microbiome in industrialized societies increases susceptibility to a variety of diseases.
“Restoration of the human microbiome must become a priority for biomedicine,” he wrote.
But how representative are these samples of a true ancestral microbiome, if indeed there is such a thing?
“Today there is no such thing as a truly isolated, uncontacted community,” Dr. Kostic said. To see ancient microbiomes, he said “we really need to go back in time.”
He and his colleagues, using modern DNA sequencing techniques, managed to do just that. They obtained eight samples of human paleofeces from arid caves and rock shelters in the Southwestern United States and Mexico and reconstructed some of their microbial genomes. The microbes they found, Dr. Kostic said, resembled those of people in nonindustrialized societies.
Those microbes helped people digest a wide variety of fibrous foods in huge quantities. Hunter-gatherers eat more than 50 grams of fiber each day, Dr. Kostic said, while the typical American eats about 10 to 15 grams of fiber a day.
“If I were to try to boost my fiber intake to, say, 30 grams, I could not do it without painful G.I. symptoms,” Dr. Kostic said, referring to the gastrointestinal tract. And, he adds, he knows that from experience. “I have tried,” he added.
That raised the question: Would people in industrialized societies gain some beneficial microbes simply by changing their diets to ones more like the traditional Hadza diet?
That might depend on whether small amounts of any of those microbes still exist in the colons of people today.
Dr. Sonnenburg, his research partner and wife, Erica Sonnenburg, and their colleagues tested that idea with mice fed a low-fiber diet. After four generations on this diet, those microbes were lost for good. “Giving the animals a high fiber diet did not bring them back,” Dr. Sonnenburg said. Adding the lost microbes back with fecal transplants is unlikely to help — the microbes are unlikely to find a niche where they could survive and multiply enough to make a difference.
Dr. Sonnenburg and others are trying to find ways of giving potentially beneficial ancient microbes a fighting chance by, for example, incorporating beneficial genes from ancient microbes into bacteria that already have a niche in the gut.
Country Microbes and City Microbes
Despite the enthusiasm for rewilding, there is no good evidence yet that adding microbes to the guts of people in industrialized societies will improve health. Correlations between nonindustrialized societies’ microbiomes and an apparent protection from diseases like diabetes do not mean that changing the microbiomes of people in industrialized societies will give them the same protection.
Keolu Fox, an anthropologist and genomics researcher at the University of California, San Diego, calls the idea that such microbes will offer protection “Just So Stories,” after the tales by Rudyard Kipling. It is easy to build a narrative based on correlations, he said.
Researchers have a challenge ahead connecting the microbes and these diseases, Dr. Gordon said.
“A lot more needs to be done to figure out what these organisms actually do and whether they do the same things in different microbial contexts,” he said.
For Katie Pollard, director of the Gladstone Institute of Data Science and Biotechnology in San Francisco, finding cures for autoimmune diseases is not just an academic exercise. She has two chronic inflammatory conditions, irritable bowel disease and ankylosing spondylitis, and her son has Crohn’s disease.
“I would love for my son to get better. And myself,” she said.
And while she agrees that “the microbiome plays a role in these illnesses,” she questions the strategy.
“Even if a modern Hadza person wanted to donate, how could this be the solution when microbiomes change on a day-to-day basis based on what goes into our bodies?” She added that “It’s a huge leap to say, ‘Let’s go back to a microbiome found in a nonindustrialized population.’”
Dr. David Relman, professor of medicine, microbiology and immunology at Stanford, had similar concerns.
“We have a certain ‘grass is greener’ attitude. We wish for the olden days when life was simpler and we hadn’t messed with the world the way we have today.” But in the olden days, he added, “life expectancy was much, much shorter and people died of infections before they ever could get cancer.”
He recalls a debate he had on rewilding at a conference a few years ago in New York with Dr. Blaser when he spoke about saving the microbiomes of the Hadza.
“I said, ‘if I have to live in New York City, I don’t want the microbiome of the Hadza,’” Dr. Relman said. The environment in New York is much different than in rural Tanzania, he noted, adding, “I am pretty sure my microbiome has figured out how to manage it.”
Wild and Unfree
But even the environment in rural Tanzania has changed, said Shani Mangola, a 31-year-old Hadza man, speaking in a telephone call from the country. Mr. Mangola was born and raised in Tanzania’s bush. He lived in the United States to study at the University of Arizona, and then returned to live among his people. He said the changes to the area and Hadza society began even before scientists studying rewilding appeared.
“Most of the Hadza here are less dependent on hunting,” he said. Wild game are scarce and the Hadza have been pushed off land where they used to hunt. Now, he said, the Hadza “beg for food or beg the tourists, ‘give us a little bit of money.’”
He added that local guides and tour companies tell the Hadza: “Don’t use the phone. Just live like the Stone Age.” In return he said, the guides give the Hadza a pittance.
The anthropologists, Mr. Mangola added, discourage Hadza people from eating modern food. “They come with small gifts — a knife, the blankets,” he said.
“Yeah we live in the bush because we don’t have any choice,” Mr. Mangola said. He and Alyssa Crittenden, an anthropologist at the University of Nevada, Las Vegas, have started a mutual aid group to raise money to send Hadza children to school.
The situation Mr. Mangola describes is part of what bothers Dr. Fox, who asked what, if anything, the Hadza or other groups have to gain from donating fecal samples to researchers. He called the rewilding hunt for microbes “predatory and imperialistic,” another example of Western researchers benefiting from data drawn from an Indigenous population that gets no say in how the findings are used or who profits from them.
Complicating work with the Hadza is Jeff Leach, who for a time was a prominent rewilding researcher and co-author on leading papers.
“He’s not really considered part of this field,” said Dr. Sonnenburg. “Everybody just wants him to go away.”
Critics say that Mr. Leach’s experiment on himself was not based on sound medical science, but that is the least of his problems. Researchers have turned against him, saying he appears not to have the advanced training that is typical in the field. And they are disturbed by the sexual assault charges that were brought against him.
A woman in Texas filed charges of assault in 2019. Mr. Leach denied the allegations and filed a defamation lawsuit against the woman. In February of 2020, a judge dismissed the lawsuit. Mr. Leach appealed the dismissal.
After the first woman filed assault charges, three other women filed affidavits making allegations that Mr. Leach sexually assaulted them. A grand jury indicted Mr. Leach, who refused a plea deal last December. A jury trial is pending. Mr. Leach’s lawyer, Rae Leifeste, did not reply to repeated requests to discuss the matter or to provide contact information for Mr. Leach.
Although the two men shared authorship on the prominent 2017 paper on microbiome diversity in Science, Dr. Sonnenburg says he and Mr. Leach never met. They were part of a collaborative network of researchers, he said. But, Dr. Sonnenburg added, “I don’t think there is any credible evidence that any of the data he gathered is problematic.”
Whatever becomes of Mr. Leach, the rewilding debate quite likely will not go away. And, Dr. Carmody and other critics say, it is not just an argument among academics but an issue that, depending on how it is resolved, can affect millions of people, for good or for ill.
With trillions of microbes in the microbiome, “you end up with a complexity we don’t yet understand,” Dr. Carmody said.
She added, “Trying to manipulate the microbiome to improve human health is premature.”
Read more at:
https://www.nytimes.com/2021/07/19/health/human-microbiome-hadza-rewilding.html
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