Self & Other · The Border Towns
The Gut, Properly
Beneath the dead outer layer is a layer of living cells, then a layer of connective tissue, then everything else. Macrophages live throughout. Specialized dendritic cells called Langerhans cells live in the upper layers, sampling whatever has gotten through. If anything truly worrying does get through, the alarm goes out and the cells we met in Chapter 2 swarm in.
But mostly, this doesn’t happen. Mostly, your skin works the way a wall works — by being there. The interesting border, the busy one, the one where the actual diplomacy happens, is the one inside you.
The Gut, Properly
Of those thirty-eight trillion bacteria we started this chapter with, the overwhelming majority — something like ninety-five percent of them — live in your large intestine.
The community is enormous and diverse. A typical adult gut contains somewhere between five hundred and a thousand different bacterial species, plus various fungi and viruses, all coexisting in a kind of slow, churning ecosystem. The composition is different in every person; identical twins are no more similar in gut bacteria than unrelated friends who eat the same diet. The community shifts when you change what you eat, when you take antibiotics, when you travel, when you get sick. It is not a fixed inventory. It is a living place.
We call this community the microbiome, and there’s been so much hype about it in the last fifteen years that the word has started to feel a little tired. Some of the hype is justified. Some of it is not. Let’s separate them.
What is genuinely true: your gut bacteria do real, useful work for you. They digest fibers your own enzymes can’t break down, releasing energy and nutrients you would otherwise lose. They produce vitamins — a meaningful fraction of your daily vitamin K, for instance, comes from your gut bacteria, not your diet. They occupy ecological niches that would otherwise be available to dangerous bacteria, simply by being there first. They release small molecules that influence your metabolism, your immune system, possibly even your mood. Without your microbiome, you would be sicker, hungrier, and more vulnerable. People whose microbiomes are wiped out by aggressive antibiotic treatment can become seriously ill, and one of the more dramatic recent developments in medicine is the use of fecal transplants — yes, exactly what they sound like — to restore a damaged microbiome from a healthy donor. It works remarkably well. It saves lives. It is also, justifiably, the kind of thing nobody likes to talk about over dinner.
What is overhyped: most of the popular claims linking specific gut bacteria to specific outcomes — weight loss, depression, autism, longevity, IQ — are running far ahead of the evidence. There are real, careful studies suggesting links. There are far more bad studies, badly reported, that imply you can fix any aspect of your life by eating the right yogurt. The truth is messier. The microbiome matters. We don’t yet know exactly how, for most things. The honest version of microbiome science right now is “very interesting, very early, watch this space.”
But for the purposes of this chapter, the question is narrower. Why doesn’t your immune system, sitting just on the other side of the thin lining of your gut, react to those trillions of bacteria the way it would react to the same bacteria anywhere else in your body? If you took some of your perfectly normal gut bacteria and injected them into your bloodstream, you would get sepsis and possibly die. Sitting in your colon, they are not just tolerated but encouraged. What’s the difference?
The Negotiation
The lining of your gut is, in immunological terms, the busiest piece of real estate in your body. Roughly seventy percent of your immune cells — yes, seventy percent — live in or near the gut. The system here is enormous, and it works on rules that are not quite the same as the ones we’ve been describing.
The lining itself is a single layer of cells called enterocytes, glued tightly together with proteins called tight junctions that, when working properly, leave essentially no gap between one cell and the next. Bacteria sit on the inside surface of this layer, and almost none of them ever cross. The first rule of the border is: stay on your side.
But the enterocytes are not alone. Sitting between and below them is an entire infrastructure dedicated to monitoring what’s happening on the bacterial side without provoking a fight.
Specialized cells called M cells deliberately sample tiny amounts of gut contents and pass them down to immune cells underneath. Other cells produce mucus — actually two distinct layers of mucus in the gut, an inner layer that is essentially bacteria-free and an outer layer where bacteria are allowed to live. (The two-layer mucus system was only properly described in 2008. Things you might have assumed were figured out a century ago, in many cases, were not.) Throughout the gut wall, in clusters called Peyer’s patches, are concentrated populations of B cells and T cells specifically tuned to gut antigens, doing a kind of immune work that is different from anything the rest of the body does.
The B cells in the gut produce a special kind of antibody called IgA, which is different from the antibodies that circulate in the bloodstream. IgA is secreted into the gut, where it coats bacteria — not to kill them, but to keep them politely on their side of the line. Most of the bacteria in your gut have IgA antibodies stuck all over them right now. The antibodies do not destroy them. They just keep them where they belong.