Bonus: When Cleanliness Makes Us Sick

In 1989, British researcher David Strahan noticed a troubling trend. Rates of hay fever had skyrocketed over the preceding thirty years, leading him to dub it a “post-industrial revolution epidemic.” Asthma and eczema were climbing too. So, he set out to find an explanation.

Strachan started with a sample of over 17,000 British children born during one week in March 1958. He studied the epidemiology of hay fever as they developed up until the age of 23. He examined 16 perinatal, social, and environmental factors and found a striking association: family size and birth order.

The more children in a family, and the younger the child, the lower the risk of hay fever. Strachan theorized that infections from older siblings might actually protect younger ones. The constant swapping of germs in childhood - runny noses, shared toys, muddy shoes in the house - could be teaching the immune system tolerance. He called this the “hygiene hypothesis.”

But not everyone was convinced. In 2003, microbiologist Graham Rook introduced his own theory. He argued Strachan’s idea was too narrow. The problem wasn’t just a lack of childhood infections. The real issue lay in our evolution. Our bodies had lost contact with the microbes that were part of our environment and biology from our earliest days. He called these our “old friends.”

According to Rook, the old friends are invaders; they’re instructors. They live in soil, untreated water, the animals, and plants that make up our ecosystem. For most of human history, they were everywhere - shaping our immune system, teaching it to distinguish between real threats and harmless bystanders. Without them, our immune system gets restless. It overreacts. It causes inflammation.

Since then, Rook has expanded his conception of “old friends” to apply to more illnesses. Lacking the necessary immune training to this variety of microorganisms, he says that vulnerable people are at significantly increased risk of mounting inappropriate inflammatory attacks on harmless environmental antigens (leading to asthma), benign food contents in the gut (leading to inflammatory bowel disease), or self-antigens (leading to any of a host of autoimmune diseases).

Rook’s 2010 paper takes this a step further. He argues that modernity’s absence of old friends, and the resulting inflammation, may promote major depressive disorder, the diagnosis we understand colloquially as depression.

Rook references “depressogenic cytokines.” These are pro-inflammatory signaling proteins from the immune system that can negatively affect brain function. They can be released in response to various stressors, including infection, chronic illness, and psychological stress. When these proteins travel to the brain, they can cause changes in neurotransmitter systems, neuroendocrine pathways, and neural circuits that result in depressive symptoms. 

By increasing background levels of depressogenic cytokines and may predispose vulnerable individuals in industrialized societies to mount inappropriately aggressive inflammatory responses to psychosocial stressors, again leading to increased rates of depression.

The study by Rook and colleagues makes the case directly: depression is increasingly tied to inflammation. Elevated inflammatory markers like cytokines are found in many people with major depressive disorder. Patients with high inflammation are less likely to respond to antidepressants. Stress — the kind we’re all bathed in from work, relationships, or the grind of modern life — can amplify the problem by pouring gasoline on the inflammatory fire. If the immune system lacks the regulatory “brakes” once provided by old friends, the result is a runaway response. The body overproduces inflammatory signals, and the brain pays the price: dulled mood, slowed thinking, and the kind of heavy fatigue that feels like moving through mud.

Rook’s team even points out that the same immune pathways that cause hay fever or eczema may also be fueling depression. In other words, the rising tide of inflammatory disorders in industrialized societies — allergies, autoimmune disease, and yes, depression — may share the same root cause: disconnection from our microbial environment.

And here’s where food enters the picture. Once upon a time, our meals were alive with microbes — fresh produce pulled from the earth, raw milk, fermented foods that bubbled with bacteria. Today, most of our diets look nothing like that. Ultra-processed foods are engineered to last on shelves, stripped of microbial diversity, sterilized by heat and chemicals. Even the “healthy” foods in the supermarket are often washed, pasteurized, and packaged within an inch of their lives. The microbial richness that once trained our immune systems has been bleached and bagged out of existence.

So the loss of old friends isn’t just about sanitized apartments or antibiotics. It’s also about what’s on our plates. A diet dominated by ultra-processed foods doesn’t just starve the gut microbiome — it deprives the immune system of the feedback it needs to stay balanced. And when the gut and the immune system lose their rhythm, the brain feels it. The connection runs from the soil to the stomach to the synapse.

For me, this is where the irony lands heavy. I grew up with brothers who tracked dirt into the house, with meals that came more from the backyard garden than the frozen aisle. Today, I often catch myself grabbing convenience foods, sterilized and sealed, in the name of efficiency. And I wonder: how much of the resilience I built as a kid was thanks to microbes I didn’t even know were there? And what happens to us — to our moods, our minds, our collective sanity — when a whole generation grows up without them?

The takeaway isn’t to abandon hygiene or eat raw chicken. It’s to see the bigger picture: depression may be, in part, a disease of disconnection. Not just from community, nature, or meaning — but from the microbial world that kept our bodies and minds in balance for millennia. And if that’s the case, then maybe healing the epidemic of depression will require more than therapy and medication. Maybe it will require repairing our oldest relationship: the one between food, microbes, and us.