Human microbiome

What is the human microbiome?

The ‘forgotten organ’ of the human body (Cenit, Matzaraki, Tigchelaar, & Zhernakova, 2014), the microbiome is defined as ‘the entire collection of genes found in all of the microbes associated with a host’ (American Academy of Microbiology (AAM), 2013). Although the majority of these microbes are bacteria, this also includes archaea (single-celled micro-organisms), fungi, protozoa, and viruses. Every individual has a particular set of microbes: estimates suggest they outnumber human cells from anywhere between 1.3 and 10 times (Abbott, 2016; Cenit et al., 2014).

The human gut is thought to house one of the densest known communities of microbes on Earth (AAM, 2013). Microbes also colonise the oral cavity, skin, lungs, nasal passages and urogenital tracts. Although the microbiome varies between people, it remains relatively stable over time. Individuals living in the same environment are likely to share similarities in their microbiota composition. Interestingly, the microbiota on different sites vary: an individual’s skin microbiome is more likely to be similar to the skin microbiomes of other individuals than to their own gut microbiome (AAM, 2013).

In the past, it was difficult to identify what microbes constituted the human microbiome, as they did not culture well in the laboratory setting. However, with advances in genome sequencing techniques, more is known than ever before about the species that comprise the microbiome and the variability between individuals, with recent research focusing on the factors that influence changes in our microbiota and how this can affect our health, risk of disease and response to treatments.

What affects the composition of the human microbiome?

We acquire the majority of our microbiome from other humans. There is some evidence of microbial transmission in utero, but the first significant colonisation occurs at birth. Babies born vaginally are colonised by maternal vaginal and faecal bacteria; those born by Caesarean section are colonised by microbes on the mother’s skin and from the hospital environment (Cenit et al., 2014). Breastmilk supplies more probiotic microbes to the baby, i.e. beneficial bacteria. It also provides complex carbohydrates and glycosylated proteins, which are prebiotics; these cannot be digested by the infant, but serve as nutrients to certain colonies of bacteria, such as Bifidobacteria. These are believed to protect against pathogens and are dominant in the microbiome of a breastfed infant. Formula-feeding leads to a different microbiome, which is more diverse and contains higher levels of Bacteroides, Clostridium and Enterobacteriacaeae. The microbiome becomes increasingly diverse as the child weans. By the age of 2.5 years, the child’s microbiome resembles that of an adult (Dinan, Stilling, Stanton, & Cryan, 2015).

Although it is then relatively stable, the human microbiome has the capacity to change in response to various factors, e.g. diet, medications, exercise, the environment and even stress; microbial shifts have been shown in pregnant mice subjected to stressful stimuli (Dinan et al., 2015). A diet rich in fibre, fruits and vegetables is thought to encourage a healthy microbiome, as are probiotic-rich foods, e.g. yoghurt, miso and sauerkraut, and prebiotic foods, e.g. raw garlic, leeks and onions. Medications, e.g. antibiotics and proton pump inhibitors, can cause significant disruption to the microbiome (Cenit et al., 2014).

Human microbiome in health and disease

The capacity for the microbiome to change provides an exciting means by which humans can potentially modulate their own health and illness. However, the biggest challenge in this field is determining whether the microbial changes associated with diseases are causal or consequential. There is promising research into the role of the microbiome in the gut, immune system, brain development, obesity and infection.

The gut

Gut microbes digest many of the carbohydrates that we ingest, with human cells being able to only digest a small proportion of them. Thus, the microbes help extract energy and nutrients from our diet, both for themselves and the human host. They also affect the metabolism of some drugs, e.g. digoxin, and aid in the synthesis of certain vitamins (Cenit et al., 2014).

Studies, primarily in mice, have shown a correlation between changes in the gut microbiome and many conditions, including obesity, diabetes, cancer, heart disease, asthma, arthritis, anxiety, insomnia, autoimmune disorders, coeliac disease, irritable bowel syndrome and inflammatory bowel disease (Bull & Plummer, 2014).

The immune system

Alterations of microbiota can cause immune dysregulation, with evidence from mice studies suggesting that this may lead to autoimmune diseases (Cenit et al., 2014). The precise mechanisms of this effect are unclear. It is posited that the increasing emphasis on hygiene in the last century has limited our exposure to a diverse range of microbes that actually complemented the human body, and that this could be a reason for the increase in allergies and autoimmune disorders (Dinan et al., 2015).

Brain development

The microbiome is thought to play a role in brain development and cognitive function, with studies showing that the brain’s serotonergic system does not develop properly in germ-free mice. Gut bacteria produce a variety of neurotransmitters, including dopamine, gamma hydroxybutyrate, noradrenaline and serotonin. Furthermore, germ-free mice have been shown to exhibit autistic-like behaviour and altered sociable traits, and children with autism have been shown to have lower levels of Prevotella, Coprococcus and Veillonellaceae than healthy controls (Dinan et al., 2015).

Obesity

Studies suggest that the microbiome can affect body fat accumulation. Individuals with reduced microbial diversity in the gut show increased adiposity, higher levels of insulin resistance and dyslipidaemia (Cenit et al., 2014). In both humans and mice, obesity is associated with reduced microbial diversity, higher levels of Firmicutes and reduced levels of Bacteroides. Some studies suggest that those children who show higher levels of Staphylococcus aureus and lower levels of Bifidobacteria in the gut are more likely to be overweight in adulthood.

Germ-free mice inoculated with the microbiome of an obese human donor gain more fat than those inoculated with the microbiome of a lean individual, even when they are fed the same diet (AAM, 2013). Overweight mice who are given the microbiome of post-gastric bypass mice, but have not been operated on, lose weight. Although there are certain groups of gut microbes that correlate with obesity, when obese individuals lose weight, their microbiome gradually becomes similar to that of lean people. This raises the question which came first?

Infection

Microbes throughout the body, including the gut, skin and oral cavity, protect against pathogens (Cenit et al., 2014). Knowledge of the microbiome can also help to treat disease, e.g. in Clostridium difficile infection. This infection is more likely where the gut microbiome has reduced diversity. Studies have shown that faecal transplant, to restore gut microbial diversity, is a highly effective treatment (Cenit et al., 2014), suggesting a causal role of the microbiome.

Future advances

Research regarding the role of the microbiome in disease processes and treatments is still very much in its early stages. More work is needed to determine the role of the microbiome in disease and how the microbiome interacts with the human genome. The key question is: are the changes in the microbiome a cause or consequence of disease?

As we improve our understanding, it may be possible to prevent disease or develop novel treatments by altering the microbiome to influence disease progression. Furthermore, it may be possible to predict the risk of specific diseases based on a patient’s gut microbe profile (Cenit et al., 2014). The lifestyle advice we offer patients may expand to include specific advice on improving the composition of the gut microbiome.