The Marginalian
The Marginalian

Our Microbes, Ourselves: How the Trillions of Tiny Organisms Living Inside Us Are Redefining What It Means to Be Human

Being alone may be the central anxiety of our time but, as it turns out, you are never really alone — at least in a biological sense: Every single cell of you — that is, every cell made of human DNA — is kept company by ten cells of microbes that call your body home. And because microbes are single-celled organisms that each carry their own DNA, the difference is even starker in genetic terms — you carry approximately twenty thousand human genes and two to twenty million microbial ones, which makes you 99% microbe. What’s more, although you and I are 99.99% identical in our human DNA, we are vastly different in our individual microbiomes — you have only one in ten of my microbes. Even more striking than the sheer number of these silent and invisible cohabitants is their power over what we consider our human experience — they influence everything from our energy level to how we handle illness to our moods to how tasty we are to mosquitoes.

The enormous implications of this micro-scale relationship, implicated in conditions as diverse as obesity, anxiety, arthritis, autism, and depression, are what Rob Knight explores in the deeply fascinating Follow Your Gut: The Enormous Impact of Tiny Microbes (public library) from TED Books, who have previously published journalist Pico Iyer on the art of stillness and mathematician Hannah Fry on the mathematics of love.

Knight, a Professor of Pediatrics and Computer Science & Engineering and Director of the Microbiome Initiative at the University of California, San Diego, writes:

You are made up of about ten trillion human cells — but there are about a hundred trillion microbial cells in and on your body. Which means: you are mostly not you.

But we are not, as we have thought, merely the unlucky hosts to the occasional bad bug that gives us an infection. In fact, we live in balance with a whole community of microbes all the time. Far from being inert passengers, these little organisms play essential roles in the most fundamental processes of our lives, including digestion, immune responses, and even behavior.

Our inner community of microbes is actually more like a collection of different communities. Different sets of species inhabit different parts of the body, where they play specialized roles. The microbes that live in your mouth are distinct from those residing on your skin or in your gut. We are not individuals; we are ecosystems.


We’re discovering that microbes are deeply integrated into almost all aspects of our lives. Indeed, microbes are redefining what it means to be human.

And yet all this incredible complexity was practically unknown to us a mere forty years ago — a sobering testament to how inconstant knowledge is and how illusory our sense of its completeness. (Astrophysicist Marcelo Gleiser captures this beautifully in his manifesto for living with mystery, in which he writes: “We strive toward knowledge, always more knowledge, but must understand that we are, and will remain, surrounded by mystery.”) Knight considers the staggering disconnect between our longtime obliviousness to the single-celled universe and its far-reaching dominion:

Single-celled organisms are more diverse than all of the plants and animals combined. As it turns out, animals, plants, and fungi; every human, jellyfish, and dung beetle; every strand of kelp, patch of moss, and soaring redwood; and every lichen and mushroom — all the life we can see with our eyes — amount to three short twigs at the end of one branch on the tree of life.

So staggering is this diversity that not only are the microbes on your hands 85% different from those on mine — meaning we each have a microbial fingerprint — but the microbes on your left hand are even different from those on your very own right hand.

Inspired by the theory of biogeography developed by the great British biologist and anthropologist Alfred Russel Wallace — Wallace, Darwin’s contemporary and the underdog of the race for evolutionary theory, mapped the relationship between land area and species diversity — Knight collaborated with University of Colorado evolutionary biology and ecology professor Noah Fierer to develop a similar way of mapping computer keyboard area and microbial species diversity. They came up with what they call the “Wallace line” between the letters G and H — the fault line of mingling for the microbial populations of your left and right hand, which each colonize the respective half of the keyboard.

Here is some perspective for our human solipsism, which tends to grasp things not in absolute terms but in terms relative to us: You carry about three pounds of microbes in your body, which renders your microbiome one of your largest organs — around the same weight as your brain. But more than a mere static presence, this hefty microbiome is an active agent in your dynamic state of being. Knight points to one particularly pause-giving point of impact — the growing body of evidence that our microbiome affects our behavior, shaping “who we become and how we feel”:

It turns out that, rather than too few mechanisms, there are almost too many to contemplate.

From their throne in our guts, microbes not only influence how we digest food, absorb drugs, and produce hormones, but they can also interact with our immune systems to affect our brains. Together the various interactions between microbes and the brain are called the microbiome-gut-brain axis, and understanding this axis could have profound implications for our understanding of psychiatric disorders and our nervous system.

Among the potential applications of this understanding is the promise of alleviating the physiological and psychoemotional burdens of obesity:

Sometimes our genes determine which bacteria live inside us, and then those bacteria turn right around and influence how we behave. This is very well demonstrated in mice lacking a gene called Tlr5, which makes them overeat and subsequently become obese. Mice missing Tlr5 have microbes that make them hungrier; they overeat and become fat. We can prove it’s the microbes doing this in two separate experiments. In one, we transfer the Tlr5-less mice’s microbes into other genetically normal mice, which then overeat and become fat. In the other study, we use antibiotics to wipe out the microbes in the Tlr5-less mice and watch as their appetites return to normal. It’s amazing to think a genetic tweak can create gut microbes that affect behavior and that this behavior can be transferred into another stomach and alter the behavior of its formerly normal host.

Knight points to similar studies being done on inhibiting anxiety by introducing microbes from anxiety-free mice to anxious mice, and considers the imminent development of vaccines against stress, PTSD, and depression. He points to one particularly promising area of study:

According to the World Health Organization, depression is now the leading cause of disability in the United States and is rapidly becoming more common in the developing world. This increase in depression rates matches the rise of other diseases frequently considered to be Western, such as inflammatory bowel disease, multiple sclerosis, and diabetes, all of which, we now know, have both immune and microbial components. Could our estranged soil bacteria, which modulate the immune system, be playing a role? In experiments in mice, Mycobacterium vaccae, a soil bacterium, has reduced anxiety. Intriguingly, in a social stress situation (essentially, smaller mice are put in a cage with a much larger, dominant mouse, which beats them up), M. vaccae treatment makes the mice much more resilient against the effects of stress, possibly providing a model for treating stress disorders in humans.

But far beyond the realm of lab mice, we’re conducting everyday experiments on our human microbiome all the time, usually without realizing it — Knight points out that everything from our diet (for instance, the balance of grains and proteins we eat and our your alcohol intake) to the antimicrobial hand-soap we buy to our use of antibiotics alters our microbiome.

Indeed, one of the most important aspects of Knight’s book, far beyond its scientific fascination, is its role as a vital public service announcement against the misuse and overuse of antibiotics — an outcry against the monoculture of mainstream medicine and a call for reclaiming our agency in the handling of our own bodies.

Pointing out that vaccines have “saved more lives throughout the world than any innovation except clean water” and are thus “humanity’s greatest triumph in public health,” he turns a critical eye toward the ludicrous anti-vaccination movement, lamenting “how much people worry about vaccines and how little they worry about antibiotics.”

A quick primer here: Antibiotics work by killing harmful bacteria in our bodies with poison that is more toxic to them than it is to us. But because bacteria breed rapidly, they also adapt to evolutionary pressures fast. Antibiotics exert one such pressure, which means bacteria swiftly sidestep the poison’s effect by developing resistance to it. Like the spammers who are constantly outsmarting and bypassing our anti-spam systems, we end up bombarded with unwanted, harmful material despite our ephemeral defenses.

But apart from being largely ineffective in the long run, antibiotics have a darker and far more significant downside — they tamper with our microbiome, sometimes modifying it to a dangerous degree. They are especially perilous for newborns and young children — Knight notes that antibiotics in the first six months are associated with weight gain (which is hardly surprising, given we use antibiotics to fatten up livestock) and may put the child at greater risk for obesity in adulthood:

Antibiotics can have a profound effect on a child’s microbial development, which may account for their apparent influence on later obesity.


Antibiotic treatment of newborns, even briefly, causes significant alterations to the composition of their gut bacteria. Perhaps more worrisome, antibiotics disturb the normal patterns of colonization of Bifidobacterium, one of the beneficial microbes. Colonization by Bifidobacterium plays a critical role in the development of a child’s immune system. Antibiotic use early in life may thus elevate the risks of allergies and allergic asthma by reducing the beneficial effects of microbial exposure.

But we are creatures of instant gratification, which is probably why we are so much more accepting of antibiotics, even if they are far more dangerous, than we are of vaccines — we take antibiotics when we are ill and they make us feel better almost immediately, almost miraculously; we are given vaccines when we are healthy, in the hope that they prevent some far-off future illness which, if they perform their respective medical miracle and work, we actually never get to experience. It’s easy to choose something that works easily and quickly, however perilous the side effects, to something that works invisibly and with greatly delayed gratification, even if it’s the safest life-saver.

In the remainder of the altogether illuminating Follow Your Gut, Knight goes on to explore how we get our microbiome and what we can do to optimize it for better physical and psychological health, both as individuals and as a culture. Complement it with Knight’s TED talk, which planted the seed for the book:

Illustrations by Olivia de Salve Villedieu

Published May 1, 2015




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