I Contain Multitudes: The Microbes Within Us and a Grander View of Life

by Ed Yong

human mothers, for some reason, churn out an exceptional variety – scientists have identified over 200 human milk oligosaccharides, or HMOs, so far.32 They are the third-biggest part of human milk, after lactose and fats, and they should be a rich source of energy for growing babies. But babies cannot digest them.

Here’s a clue: these sugars pass through the stomach and the small intestine unharmed, and land in the large intestine where most of our bacteria live. So, what if they aren’t food for babies at all? What if they are food for microbes?

As it digests HMOs, B. infantis releases short-chain fatty acids (SCFAs) that feed an infant’s gut cells – so while mothers nourish this microbe, the microbe in turn nourishes the baby.

He always saw it as a positive force, one that provides both partners with benefits and opportunities. But it can also be a trap, where the partners become increasingly vulnerable in their dependency.

A full third of reef-building coral species face extinction, imperilled by many threats.

a diverse microbiome, through its mere presence, creates a blockade against disease. This effect is called colonisation resistance.

the algae were making something that killed the corals via their own microbes.

They are called black reefs. They are a marine vision of Tolkien’s Mordor, and they happen when a boatload of iron lands in an ecosystem that is generally poor in nutrients. The iron acts as fertiliser for fleshy algae, which grow so vigorously that even grazing fish can’t trim them back fast enough.

“Even though coral reefs are incredibly complex, microbes are the main determinants of [their] health and decline.”

Rohwer’s work with corals hints at a different type of microbial disease, one without a single obvious culprit.4 These illnesses are caused by communities of microbes, which have shifted into configurations that harm their hosts. None is a pathogen in its own right; instead, the entire community has shifted to a pathogenic state. There’s a word for such a state: dysbiosis.5 It is a term that evokes imbalance and discord in place of harmony and cooperation. It is the dark reflection of symbiosis, the antithesis of all the themes we have seen so far.

That’s dysbiosis. It’s not about individuals failing to repel pathogens, but about breakdowns in communication between different species – host and symbiont – that live together. It is disease, recast as an ecological problem.

Healthy individuals are like virgin rainforests or lush grasslands or Kingman Reef. Sick individuals are like fallow fields or scum – covered lakes or the bleached reefs of Christmas Island – ecosystems in disarray. This is a more complicated view of health, and one that raises important questions. Foremost among them: are such changes the cause of disease, or merely its consequence?

It was a stunning result: Turnbaugh had effectively transferred obesity from one animal to another, simply by moving their microbes across.

Akkermansia muciniphila, one of the more common species of gut bacteria, is over 3,000 times more common in normal mice than in those genetically predisposed to obesity. If obese mice eat it, they lose weight and show fewer signs of type 2 diabetes.

Without fibre, the lean communities couldn’t establish themselves or stop the mice from putting on weight. They could only infiltrate the guts of mice that ate healthily. The old dietary advice still stands, overenthusiastic headlines be damned.

This is the essence of the hygiene hypothesis and its various spin-offs: exposure to a broader range of microbes can change the microbiome and suppress allergic inflammation – at least in mice.

But pets are not our most important sources of old microbial friends. That honour goes to our mothers.

This might explain why C-section babies are more likely to develop allergies, asthma, coeliac disease, and obesity later in life. “The baby’s immune system is naïve at birth and whatever it sees first will start its education,” says Dominguez-Bello.

“if you go for a C-section and bottle-feeding, I’d certainly say that [your baby] is on a different trajectory,”

But antibiotics are shock-and-awe weapons.

Blaser’s work suggests one possible explanation: the drugs disrupt the microbiome, leading to weight gain.

We are heading into a terrifying post-antibiotic era.

Decent sanitation has been an unquestionable public health good, sparing us from many infectious diseases. But we have taken it too far.

We have taken cleanliness to mean a world without microbes, without realising the consequences of such a world.

This work underscores an important principle: we will only learn if developed countries truly lack important microbes by studying a broad swath of humanity.

WEIRD countries – that is, Western, Educated, Industralised, Rich, and Democratic.

All of these people have microbiomes that are far more diverse than those in the West. Their multitudes are more multitudinous. They also contain species and strains that are undetectable in Western samples.

There’s some evidence that a diverse microbiome is better at resisting invaders like C. difficile, and that low diversity often accompanies diseases.

As yet, no one has shown that people with less diverse microbiomes are more prone to acquiring disease. And there are cases where people with diverse microbiomes are more likely to carry certain intestinal parasites.

There are also signs that the human microbiome has been shrinking since well before the antibiotic era began, or even before the Industrial Revolution.

‘antibiotic winter’”.

They promise to let us eff the ineffable, and control the uncontrollable.

When you move away from the one-microbe-one-disease model and into the messy, multifaceted world of dysbiosis, the lines of cause and effect become much harder to untangle.

“I think that everybody is coming to the realisation that, unfortunately, a really compelling simple biomarker, like the percentage of a certain microbe, is not going to be enough to explain something as complicated as obesity,” says Katherine Pollard, who led one of the re-analyses.

DNA reveals which microbes are present and what they are capable of, but the other molecules tell you what they are actually doing.

germ-free rodents are less anxious than most),

By getting on with their usual activities, in a purely selfish way, they incidentally benefit their hosts. These “by-product mutualisms” are the perfect first handshake.6 Both partners get something out of the relationship, without either having to invest in it. The host can then evolve traits that solidify the partnership, from cells that house the tiny partners to molecular anchor-points for them to latch themselves to. And the most important of these traits – the one that does more than any other to seal a symbiosis – is inheritance.

proctodeal trophollaxis

When people think about contagious microbes, they tend to think of pathogens first. Herds, flocks, and colonies make it easier for diseases to spread. But they also create opportunities for beneficial symbionts to find new hosts.

In his classic book The Extended Phenotype, Richard Dawkins introduces the idea that an animal’s genes (its genotype) do more than sculpt its body (its phenotype). They also indirectly shape the animal’s environment.

All of these things – dams, nests, and books – are what Dawkins calls extended phenotypes. They are products of a creature’s genes that extend beyond its body. In a way, that’s what our microbiomes are. They too are shaped by animal genes, which create environments that encourage specific microbes to grow.

If animals are picky about their microbes, and microbes are picky about their hosts, and both are locked in partnerships that endure through generations, maybe it makes more sense to think of them as unified entities. Maybe we should think of them as one.

She was drawn to the connections between living things, and she realised that every creature lives in communities with many others. In 1991, she coined a word to describe this unity: holobiont, from the Greek for “whole unit of life”.22 It refers to a collection of organisms that spend significant parts of their lives together.

Their animal vehicles do too, but the genes are what natural selection really acts upon. They are, in the parlance, the “units of selection”.

To Rosenberg, it made no sense to think of these collections of DNA separately. He believed that they work as a single entity – a hologenome, which “should be considered as the unit of natural selection in evolution”.

evolution by natural selection depends on just three things: individuals must vary; those variations must be heritable; and those variations must have the potential to affect their fitness – that is, their ability to survive and reproduce.

As we know, even the most harmonious of symbioses are tinged with antagonism. Rohwer feels that Rosenberg, by positioning the hologenome as the fundamental unit of selection, is glossing over those conflicts.

If an animal’s microbial partners can be so inconstant, does it really make sense to speak of a hologenome as a united entity?

The biochemical pathways that create amino acids work in a similar way, but neither aphids nor Buchnera can build all the necessary enzyme machines on their own. Instead, they cooperate to set up the production lines, which wind in and out of two factories, one nested within the other. Only together can they subsist on phloem sap.

On land, life is powered by sunlight. Plants, algae, and some bacteria can harness the sun’s energy to make their own food, by refashioning carbon dioxide and water into sugars. This process, in which carbon is shunted from inorganic matter into edible substances, is called fixing carbon, and using the sun’s energy to do so is called photosynthesis.