Culture Shift

The human immune system is, in one sense, a detection mechanism. It has evolved, over millions of years, to scan the body for molecular signals that tell it whether to attack or stand down. Most of these signals come from pathogens, damaged cells, or the body’s own hormones. But in 2019, a lab in Germany published a finding that pointed to a much stranger source: one of the signals sensed by the immune system is found in sauerkraut.

When people eat sauerkraut, a molecule called phenyllactic acid (D-PLA) — found in fermented foods — enters their bloodstream and activates a receptor, known as HCA3, on immune cells, triggering an anti-inflammatory response. In addition to lactic acid, phenyllactic acid is one of many compounds produced by lactic acid bacteria during the fermentation of sauerkraut and related fermented foods. Prior to this study, other molecules had been found to bind HCA3, but D-PLA was a hundredfold more potent than any of them.

This discovery advances our understanding of how fermented foods can reduce inflammation and positively affect human health. But more striking is what it suggests about hominid physiology. Although HCA3 is part of a larger family of receptors broadly conserved across eukaryotes, HCA3 is only present in humans and other great apes like chimpanzees and gorillas — and not even in other mammals. It is a recent addition to the genome, appearing only a few million years ago. Its existence seems to suggest that our immune system evolved to recognize the microbial metabolites from fermented foods.

We tend to think of fermented foods as something humans invented and then chose to eat. But, increasingly, scientific evidence suggests the causality runs the other way. Fermented foods appear to have helped shape human biology itself, and our bodies may have been built, in part, to expect them. The case for this runs from changes in hominid gut anatomy millions of years ago to the HCA3 receptor, to a growing body of research linking fermented food consumption to immune function and gut health. And it raises an uncomfortable question about what happened when the Western food system, in the name of safety and efficiency, quietly removed these foods from our diets in the nineteenth and twentieth centuries.

Early Fermentation

Fermented foods are the result of the controlled growth of communities of microbes. At their core, they are the products of the interaction of these microbes and whatever food they consume, whether cabbage or cucumber. While this process varies from food to food, fermentation typically involves managing environmental variables such as oxygen, temperature, and salinity. In contrast to food preservation methods like canning or even pickling, which are designed to prevent microbial growth, fermentation harnesses the capacity of naturally occurring microbes found on fresh food or in the environment to outcompete spoilage organisms.

Most archaeological evidence from pottery shards suggests that fermented food production is at least 7,000 to 10,000 years old. This timeframe coincides with the major transition to agrarian lifestyles, which would have reliably produced surpluses of food and the subsequent need for preservation methods. While this explanation satisfies most scholars, there is reason to believe that fermentation may be far older.

For one, it’s a very simple process to trigger. Some foods even ferment spontaneously. In the case of alcoholic drinks, like beer, wine, or mead, ubiquitous yeast species, which are naturally found on grapes and other fruit skins, rapidly use sugar as a food source for reproduction, producing ethanol as a byproduct. The same results occur when ripe fruit falls to the ground and its sugar is exposed to the environment, or when honey is diluted with water.

Other processes require only minimal intervention. For example, submerging fresh food in liquid or burying it creates a low-oxygen environment that encourages the growth of acid-producing bacteria that preserve the food by what is called “lactic acid fermentation.” This technique produces dill pickles, sauerkraut, and kimchi. While salt is often added as an additional intervention against unwanted microbes, it’s not required as it isn’t the primary driver of the fermentation.

Another argument for an earlier origin for fermented foods is that they are found across nearly all human cultures. While the number of fermented foods in the modern, Western diet is fairly limited (cheese, yogurt, bread, chocolate, coffee, beer, wine, kimchi, and kombucha) hundreds more are eaten around the world, from fermented shark in Greenland to a seemingly limitless variety of fermented soy beans in Asia. This diversity is a testament to how humans gradually mastered this ancient practice and modified it to suit new environments as they moved out of Africa.

Around 14 million years ago, our hominid ancestors were arboreal species whose diet would have been primarily based on fresh fruits picked from the trees they lived in. When ripe fruit fell to the ground and underwent spontaneous fermentation, it would have been toxic to our ancient ancestors due to its high concentration of ethanol. Their bodies as yet had no efficient way to break down ethanol.

But then, about 10 million years ago, a mutation arose in the genome of the common ancestor of humans, gorillas, and chimpanzees. This mutation, a single amino acid change in the enzyme Alcohol Dehydrogenase 4 (ADH4), enabled it to break down and detoxify ethanol with 40x higher efficiency. The capacity to consume this energy-rich but previously dangerous fruit may even have driven our transition from an arboreal lifestyle to a terrestrial one. What’s more, this ability to tolerate ethanol may have been what allowed our ancestors to diversify their diet and survive while lineages without this mutation went extinct.

The fossil record shows that a major shift in hominid anatomy occurred around 2 million years ago, when hominids developed a smaller rib cage and larger skull. At the same time, another major change took place in their intestines. Compared to our closest relatives, humans have a digestive tract that is 40 percent shorter. This decrease was thought to be driven by the external processing of our food, which reduced the time and energy involved in chewing and digesting. Anthropologist Richard Wrangham argues that the technological innovations of controlling fire and cooking food led to this major change, and that the excess energy we got from cooked food, in turn, supported the evolution of a larger brain.

However, two recent studies, by biological anthropologist Katie Amato in 2021 and evolutionary biologist Erin Hecht in 2023, suggest that these anatomical changes may have been driven by human use of fermentation even before humans began to cook. By allowing microbial species to ferment and break down complex carbohydrates and other macromolecules in foods, we may have turned over certain parts of an otherwise energy-intensive digestive process to microbes in a form of “external digestion.” This use of fermentation to pre-digest food, intentional or not, may have served as a predecessor to cooking, providing the extra calories needed to support the evolution of a larger brain.

Another benefit of fermentation is that it offered access to foods which, previously, would have been toxic. As our ancestors came down from the trees and needed new ways to fill their stomachs, the tubers of many plants and grasses offered an appealing, ready source of calories. Tubers contain large deposits of starch. Root vegetables, such as potatoes, yams, and carrots, are our modern-day, highly domesticated equivalents. But the wild tubers of our ancestors’ time were hard to chew, and some contained low levels of toxins. Varieties of cassava, for example, contain compounds that release cyanide when ingested. After just a few days of fermentation, however, microbes help remove these toxins.