The Microbiome

If you’ve been keeping up with microbiology in any way over the last half dozen years you will surely have come across the term “microbiome”. Technically, this refers to the collection of genes of all the microbes that live on or in us but, in a loosening of the terminology, has come to mean the collection of those bugs themselves. There has been an explosion of research into the human microbiome since the advent of faster and cheaper methods of sequencing genes in the past decade (called next-generation sequencing) and what we are finding out about the bugs that live in or on is both astonishing and growing exponentially. Prior to the advent of next-generation sequencing any knowledge gained about these bugs was both hard-fought and extremely limited, as the vast majority of our symbionts are non-culturable – we cannot get them to grow on Petri dishes and study them using old-school microbiology.

We are a walking ecosystem, an ark of microbes. Here are some figures: we host as many bacteria, fungi and protozoa as we have cells of our own – about ten trillion (the number one followed by thirteen zeros); we carry two to three kilos of non-self around with us; there more than one thousand species present in each of our microbiome “zones” (e.g. the mouth, the skin); the size of the genome (the collection of genes) of the bugs on or in us is about two hundred times greater than our own genome; this microbiome is composed of more than three million protein-encoding genes; we have only been able to grow on artificial media about 10-20 percent of these bugs.

There are a number of different microbiomes on or in us: that of the nasal passages, the oral cavity, the skin, the gastrointestinal tract, and urogenital tract (including, as has been recently shown, the bladder). The microbiome is dynamic and changes in response to many internal and external agents, including environmental factors such as diet and use of antibiotics. The most dramatic changes in our microbiome composition occur in infancy and early childhood, when the microbiomes of our tissues are laid down. Important factors which have been shown to affect this seeding of the infant microbiome include: gestational age (full term or premature); mode of delivery (vaginal birth or caesarean section); type of feed (breast milk or formula feeds); maternal nutritional status (overweight or undernourished) and use of antibiotics during gestation. The complexity and plasticity of the infant microbiota has an impact on health later in life.

Let’s look at some of the things our microbiome does. In the gut the gazillions of bugs present help digest our food. For example, a guy called Bacteroides thetaiotaomicron breaks down the large, complex carbohydrates found in many plant foods –up to 250 different carbs. The bugs in our gut, mouth and on our skin and possibly other locations regulate our immune system. They are in constant communication with important regulator T-cells (Tregs) and are responsible for keeping excess inflammation in check as well as “training” the infant immune system. Just by their sheer physical presence, our microbiome’s bugs can protect us against other microbes that cause disease; this barrier function is particularly important in the case of the skin, vagina and nasal passages. In our gut many bugs produce vitamins – B vitamins (B12, thiamine and riboflavin) and vitamin K. They also produce short-chain fatty acids important in host metabolism and signalling to the immune system, analgesics, antioxidants and anti-inflammatory factors. Whatsmore, they play an important role in how the body metabolises drugs – a phenomenon called pharmacokinetics. 

There are two major groups (at the phylum level) of bacteria present in the human gut – Bacteroidetes and Firmicutes. Many studies focus on the relative numbers of members of these groups and draw conclusions on health status based on this. From my study of the field, whether one has a “healthy” microbiome is a far more complex matter than the ratio between groups of bugs. 

Two concepts are very important when thinking about the microbiome: specificity and redundancy. Specificity means that each species present has their own characteristic niche. For example, Clostridiodes difficile spores will only germinate in the duodenum in the presence of primary bile salts. Redundancy means that there are many bugs capable of carrying out any give role at any position in the microbiome. If, for example, one bug which munches the sugar, mannose, gets knocked out by that tequila you drank last night, another fella who is resistant to tequila will step into the breach and happily chew away on the mannose.

There is a great variety of environments in and on us humans. Think of the mouth: you have the wet and oxygenated tongue, the deep, dry recesses of the gums where oxygen is not so plentiful, the scummy, food-rich spaces between our teeth. Our gut is as varied in habitat as a continent. From the proximal to the distal part of intestine, the oxygen levels are dramatically decreased, resulting in the dominancy of anaerobic microbes in the colon. The aforementioned Bacteriodetes burn out oxygen, attenuating the detrimental actions of oxygen species against the obligate anaerobes including commensal Clostria. Acidity also varies from stomach (acid) to colon (basic) to caecum. Firmicutes (including segmented filamentous bacteria and lactic acid bacteria similar to the bugs found in cheese and yoghurt) and Proteobacteria (Enterobacteriaceae and Helicobacter spp.) can dominate in this proximal intestine.

Given the length of the human intestine is roughly five metres (fifteen feet) and the physico-chemical environment changes every couple of inches, it is not surprising that we are only beginning to understand the complexity of the microbiome present.