Indeed, when Sonnenburg fed mice plenty of fiber, microbes that specialized in breaking it down bloomed, and the ecosystem became more diverse overall. When he fed mice a fiber-poor, sugary, Western-like diet, diversity plummeted. (Fiber-starved mice were also meaner and more difficult to handle.) But the losses weren’t permanent. Even after weeks on this junk food-like diet, an animal’s microbial diversity would mostly recover if it began consuming fiber again.
This was good news for Americans—our microbial communities might re-diversify if we just ate more whole grains and veggies. But it didn’t support the Sonnenburgs’ suspicion that the Western diet had triggered microbial extinctions. Yet then they saw what happened when pregnant mice went on the no-fiber diet: temporary depletions became permanent losses.
When we pass through the birth canal, we are slathered in our mother’s microbes, a kind of starter culture for our own community. In this case, though, pups born to mice on American-type diets—no fiber, lots of sugar—failed to acquire the full endowment of their mothers’ microbes. Entire groups of bacteria were lost during transmission. When Sonnenburg put these second-generation mice on a fiber-rich diet, their microbes failed to recover. The mice couldn’t regrow what they’d never inherited. And when these second-generation animals went on a fiberless diet in turn, their offspring inherited even fewer microbes. The microbial die-outs compounded across generations.
Many who study the microbiome suspect that we are experiencing an extinction spasm within that parallels the extinction crisis gripping the planet. Numerous factors are implicated in these disappearances. Antibiotics, available after World War II, can work like napalm, indiscriminately flattening our internal ecosystems. Modern sanitary amenities, which began in the late 19th century, may limit sharing of disease- and health-promoting microbes alike. Today’s houses in today’s cities seal us away from many of the soil, plant, and animal microbes that rained down on us during our evolution, possibly limiting an important source of novelty.
But what the Sonnenburgs’ experiment suggests is that by failing to adequately nourish key microbes, the Western diet may also be starving them out of existence. They call this idea “starving the microbial self.” They suspect that these diet-driven extinctions may have fueled, at least in part, the recent rise of non-communicable diseases. The question they and many others are now asking is this: How did the microbiome of our ancestors look before it was altered by sanitation, antibiotics, and junk food? How did that primeval collection of human microbes work? And was it somehow healthier than the one we harbor today?
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Most study subjects live in the tropics; their microbial communities may reflect tropical environments, not an ancestral human state. Yet even “extinct” microbiomes from higher latitudes—including from a frozen European mummy—are similarly configured to break down plant fiber, adding to the sense that the Western microbiome has diverged from what likely prevailed during human evolution.
The Sonnenburgs think fiber is so important that they’ve given it a new designation: microbiota-accessible carbohydrates, or MACs. They think that the mismatch between the Westernized, MAC-starved microbiome and the human genome may predispose to Western diseases.
Scientists studying these communities suspect that while mortality is high from infectious diseases, chronic, non-communicable diseases are far less prevalent. At the same time, researchers since the late 20th century have repeatedly observed that even in the West, people who grow up on farms with livestock, or exposed to certain fecal-oral infections, like Hepatitis A and sundry parasites—environments that, in their relative microbial enrichment, resemble these subsistence communities—have a lower risk of certain Western afflictions, particularly hay fever, asthma, and certain autoimmune disorders.
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As Justin Sonnenburg put it, “We have this unsupervised drug factory in our gut.” The question facing microbiologists today is how to properly tend to that factory.
Here, studies of populations living more traditional lifestyles may provide clues. In the past, most people likely imbibed many times more fiber than today. If you eat minimally processed plants, which humans have for millions of years, you can’t avoid fiber. Modern hunter-gatherers and horticulturalists certainly eat loads of it. The Hadza of Tanzania, for instance, consume at least 10 times more than Americans, in tubers, baobab fruit, and wild berries. Agriculturalists, like those Burkina Fasans, also eat more fiber than Western populations, in porridges and breads made from unrefined grains.
Given this constant supply of microbiota-accessible carbohydrates, human microbiomes of the past, the Sonnenburgs argue, likely produced a river of these short-chain fatty acids. That probably changed some with the transition to agriculture, which made diets less diverse. But an even more drastic shift occurred quite recently, with the advent and widespread adoption of refined foods. As a result, westernized populations, the Sonnenburgs think, have lost healthful, fiber-fermenting microbes. And we suffer from a kind of fermentation byproduct deficiency.
So why can’t we supplement our diet with short-chain fatty acids? When I visited Sonnenburg, he showed me one reason why: The ecosystem that produces the acids may be as important as the acids themselves. He brought up two cross-sectional images of fecal pellets still in mice intestines. Most microbiome analyses take a tally, from genetic markers, of what microbes are present and in what abundance. That’s equivalent to imagining what a forest looks like from a pile of wood chips, and gives little sense of how the forest was organized. By some ingenious tinkering, though, one of Sonnenburg’s post-docs had developed a way to freeze the ecosystem in place, and then photograph it.
The resulting picture was unlike any rendition of the microbiome I’d seen before. One animal had eaten plenty of fiber, the other hadn’t. In the fiber-fed ecosystem, similar bacteria clustered with one another, not unlike schools of fish on a reef ecosystem. An undulating structure prevailed across space. But in the non-fiber diet, not only was diversity reduced, the microbes were evenly distributed throughout, like a stew boiled for too long.
At this point, Sonnenburg sat back in his chair and went quiet, waiting for me to notice something. To one side of both images, microbes were mostly absent—the mucus layer on the lining of the gut. But that layer was twice as thick in the fiber-fed mice than the non-fiber fed. That difference amounted to about 30 nanometers, far less than the width of a human hair. But one day we may look back and shake our heads that Western diseases—from diabetes to colon cancer—stemmed from 30 nanometers of mucus that, somewhere along the way, went missing in the developed world.
We think of the Western diet—high in unhealthy fats, sugar, and proteins—as overly rich. But what’s missing from the diet may be just as, and perhaps more, important than what’s abundant.
Years ago, while still a post-doc, Sonnenburg discovered that something very odd occurs when those MAC-loving microbes go hungry. They start eating mucus. “This is the stage where you say, ‘Oh my God. They’re eating me.’ ” Sonnenburg said. “You can see it.”
