Our gut microbiota
All the cells in our bodies are evolved bacteria, and nearly all harbour evolved bacteria within them. Further, all the surfaces of our bodies are teaming with resident bacteria (and other microorganisms such as fungi or viruses). There are roughly ten times more microbes on us than there are cells in our bodies, and they contain at least 100 times more genes than we do (these numbers are constantly being revised). The more our microbes are studied, the more we realise how important our invisible companions are.
Our gut microbes are not inside us
All of our microbial colonies, whether on the skin, in the gut or elsewhere, are external to us. They are on us, not in us. I will explain using the gut as an example.
The digestive system, in total, from mouth to anus, is effectively a long and continuous tube that can be opened or closed to the outside world at either end. It’s contents, therefore, are external to us — the inside of our digestive system is outside of our bodies. We are like an elongated doughnut with an opening that runs down the middle — the dough is our ‘inside’ but the hole down the middle is outside the doughnut. If we put some food in our mouth and shut our mouth, the food is not inside us, it is in a cavity that we have created, but it is still outside our body. Likewise, bacteria on the gut wall are outside us too. If they crossed the wall into our bodies they would cause us illness. The actual inside of our bodies is kept sterile by the immune system.
This gives a different way of thinking about our microbes — they are a living barrier that stands between us and the outside world, covering all external and internalised surfaces. Consequently, they curate our interaction with our environment, everywhere that we are exposed to it.
Microbiota
The term ’microbiota’ refers to the collection of all our microbes. The body region with the greatest density of microbes is the large intestine (colon).
We also have skin microbiota, lung microbiota etc. The term ‘microbiome’ refers to the gene pool of the microbiota.
In 2012, the first comprehensive measurement of the human microbiome was published (it took 5 years to accomplish that feat). Samples were taken from the gut, skin, mouth and other regions (18 sites in all were sampled for women and 15 for men, the difference in numbers being genital). The study recruited 242 healthy Americans, but included different ethnicities, ages and other demographics. The results were a turning point in the understanding of our microbial partners — it had not generally been realised how diverse and potentially important these microbial colonies were, and now there were tools to investigate them (the number of publications related to our microbiota was in the hundreds before 2012, and >10,000 since).
However, this recency also means that many of the questions we might want to ask about our microbes do not yet have scientifically-settled answers.
What they do
Numerous studies have highlighted the roles performed by our gut microbiota. They include: resisting pathogens by competing for colonisation sites; maturation and regulation of the immune system; production of vitamins, such as B12, B5, and K, and amino acids; synthesis of some digestive enzymes (e.g. lactase); production of antibacterial and anti-fungal substances; fermentation of indigestible dietary fibres into short-chain fatty acids (such as acetate and butyrate) that fuel cells in the gut wall and elsewhere (or have signalling roles); fermentation of lactose, and; contributing to absorption of some minerals (e.g. zinc, iodine, selenium, cobalt). That’s an impressive list. Without our intestinal microbes, we would not survive well. We evolved together with our microbiota, and have outsourced these functions to them.
In return we offer them a safe haven: they populate the newborn (from the mother’s microbiota) at (or before) birth and immediately communicate with the infant’s fledgling immune system to instruct it to look after them and attack foreign species; our gut offers a regulated temperature environment (meanwhile, we freeze or sweat according to the weather); we feed them constantly — they don’t need to forage for food (we do); we use our brains to select and prepare food carefully so as to avoid pathogens that might harm them (and us) and; it’s possible we offer them a safe house when under attack — our appendix. There is speculation that in the presence of pathogens, a representative sample of our microbiota migrate there (a sort of intestinal Noah’s Ark) and wait out the infection as a back-up population.
So, it is a unique niche we offer, which perhaps explains why the density of microbes in our gut is greater than that in any other ecological environment that we know of. If there was a microbial nirvana, it would be our gut.
Epigenetics
There is another important role for our microbes that is just beginning to emerge — regulation of how we express our DNA (i.e. read our DNA to produce the proteins that make us up). One of the sobering outcomes of sequencing the human genome was that we had only about 23,000 genes. That’s about the same as a fruit-fly. An earthworm has three times that many. Our gene pool differs from that of a chimpanzee by only 400 genes (we share the other 22,600). How could we have evolved into something as complex as a human under these circumstances?
It turns out that evolution took a different turn with us. It seems that it became increasingly unwieldy to keep adding genes to our DNA to make us more adaptable. Instead, we developed the ability to use a smallish number of genes but to combine or express them in different circumstances and times to produce complexity (known as epigenetics).
It is a common way of creating complexity — think of how many books, with different stories, that have been written with the same 26 letters of the alphabet. Various factors, such as environmental, dietary, experience, career, lifestyle and mood can potentially influence our epigenetics. It makes good sense, we can use epigenetics to adapt rapidly to the circumstances and environment we find ourselves in, while our DNA evolves over millennia. It means that our DNA is not necessarily our destiny, an empowering realisation.
The astonishing thing is that our gut microbes can release signalling molecules that influence this epigenetic process. Our gut microbes have a say in what we are. As Ed Yong puts it: “…they don’t just go along for a ride; sometimes, they grab the wheel”.
They also have a say in who we are — there is much interest in what is called the ‘gut-brain axis’. These two organs can communicate (bidirectionally) via the vagus nerve. Gut microbes can release neurotransmitters (e.g. serotonin, dopamine) that can modulate gut-brain signalling (although they will not cross the blood-brain barrier) or release other molecules that have neuromodulatory behaviours (e.g. butyrate). Or, they can alter brain behaviour more indirectly, such as through the immune system or by influencing sleep or the circadian rhythm.
Some commonly-experienced examples of gut-brain signalling are: feeling nauseous when stressed; ‘butterflies in the stomach (gut)’ when nervous; a ‘gut feeling’ about something that our brain cannot resolve; even, perhaps, the satisfaction of a bowel movement. The gut microbiota are silently speaking to us, responding to us, and chattering among themselves in ways that are probably as old as biological time.
Before leaving this topic, I can’t resist mentioning the curious case of Toxoplasma gondii. This parasite is found worldwide, including in ~50% of humans globally (in whom it is mostly asymptomatic). Rodents are a favourite host for the parasite, however, it can only reproduce in the intestines of cats (or other felids). To achieve this, it’s strategy is to epigenetically modify the fear centre of the rodent’s brain (the amygdala) so that the rodent is no longer scared of cats or repelled by cat urine. This makes the unfortunate rodent more likely to end up as cat food. A dastardly way for toxoplasma gondii to complete its life cycle, but a remarkable example of gut-brain control. It may seem rather machiavellian, however, the prevalence of the parasite worldwide attests to the success of its strategy.
