What's Living Inside Me And Why Is It Important?

Humans are holobionts!

It was German theoretical biologist Adolf Meyer‐Abich, who firstly described the theory of holobiosis in 1938. The concept has subsequently evolved and today, holobiont refers to a close physical association between individuals of different species, that live in symbiosis and together form anatomical, physiological, immunological or evolutionary units.

The enormous amount of research has more than indicated that we, humans, exist in a symbiosis with our microbiome and so we are therefore holobionts, comprised of a human and a microbiome. 

Without symbiosis, life on earth as we know it today would not even exist. Symbiosis between simple single-cell organisms (prokaryotes) and microbes, was essential for the subsequent expansion of multicellular eukaryotes and the diversification of species. Our human cells carry remnants of prokaryotes in the form of mitochondria and organelles, without these we could not sustain life. The research from the last 10-20 years is helping us understand the complex symbiotic relationship between us and our microbiomes, that occupy multiple parts of our human body. Concurrently, we are in no doubt that our microbiomes are essential in our existence and interact with all organs and processes inside our body. 

What is the human microbiome and how much are we human?

The two terms, microbiome and microbiota are used interchangeably and often wrongly to mean the same thing. Just to set things straight from the beginning, your microbiota are microbes (bacteria, fungi, viruses and phages) that live in and on your body. You are less than 50% human in terms of the number of cells, they are about 65%. The microbiome is the combined genetic material inside these living microbes, which is 150-200 times the number of your human genes. Your human genome consists of about 23,000 genes, whereas your microbiome encodes over 3 million genes that produce thousands of different molecules. In terms of genes, humans are more than 99% microbial. 

Your microbiota exists in several anatomical sites; skin and genitals are popular; however, the vast majority live inside your gut and from there, they exert effects that are carried throughout your body. 

What is the gut microbiota?

There are trillions of bacteria in only 1g of your gut content and an average human can carry around 2kg. The scientific investigations of bacteria, that populate our gastrointestinal (GI) tract, date well over a century ago. In 1908, Élie Metchnikoff suggested that a targeted modification of the microbiota may prolong life and guard against senility. His recommendation was to regularly consume kefir, to delay the frailties of old age. However, the advent of antibiotics and their revolutionary success in the treatment of bacterial infections overshadowed the interest in the gut microbiota, until the very end of the 20th century. Since that time, gut microbiota research has become very popular and it has shown that these tiny organisms are essential and very influential in just about everything that goes on in your body. That includes your development, nutrition, immunity, regulation of hormones and even the way you think and experience things. 

The function and balance of bacteria, which should ideally work together to allow us to eat and digest food without discomfort, is what these days is termed gut health. 

What is gut health?

Gut health covers multiple positive aspects of the gastrointestinal (GI) tract. For example: 

• effective digestion and absorption of food

•  absence of GI illness and symptoms

• normal and stable microbiota

• effective immune status 

• state of well-being

There is a delicate interaction between you and your microbiota. The disruption of this balance can compromise the homeostasis, and even the survival of the whole holobiont. So, that has a direct effect on your health, disease, and ageing, not just in your gut but other organs that are distant from the gut, such as your skin or the brain.

Gut health maintenance involves continuous interaction between the two key functional entities, the GI microbiota and the GI barrier, consisting of epithelial defence and metabolic functions, the mucosal immune system and the enteric nervous system (ENS). The GI barrier adjacent to the GI microbiota, is the area of sampling and communication between you and your gut content, and it is the key to understanding the complex mechanisms that maintain gut health. The gut microbiota interacts here with the immune system and the vagus nerve, and its effects are then carried out throughout your body. It also helps to maintain an intact GI barrier that is closely related to infectious, inflammatory and allergic diseases, as well as aging.

The intestinal lumen is the main main habitat for the gut microbiota, as it is characterised by a constant stream of nutrients for those bacteria. Around the lumen lies the mucosa (moist, inner lining), separated by a mucus layer, whose thickness increases from approximately 20 micrometres in the small intestine to 830 micrometres in the large intestine. Its primary purpose is to protect the GI epithelium from direct contact with the commensal microbes and their metabolites.

Overall, the gut could be thought of as a reactor that processes dietary inputs to generate energy and produce and extract nutrients for use around the body. The involvement of the microbiota is critical in this function because lack of, or perturbance in, commensal bacteria results in inability to fully metabolise all the components of our diet (e.g. plant fibres) or produce all of the important bioactive molecules that we need to thrive. Bacterial processing of dietary macronutrients results in the production of different metabolites, such as short chain fatty acids (SCFA), lipopolysaccharide (LPS), EPS (exopolysaccharides, a secreted product), flagellins and small molecule metabolites that all interact with cells of the immune system. Any disregulation of the microbiota functionality contributes to our susceptibility in immune dysfunction and increases risks of acute and/or chronic disease development.

What is the composition of the gut microbiota and how is that important?

Incredibly, the precise gut microbiota composition of each individual is unique, like a fingerprint, continuously adapting to diet, lifestyle and environmental inputs. Moreover, due to differences in the nutrient availabilities and physicochemical characteristics (pH, bile acids, motility etc), distinct microbiota niches are present across the various compartments of the GI tract. The small intestine is characterised by lower numbers and less richness in bacterial species, compared to the large intestine.  Finally, differences in the microbial composition, within an individual, exist also along the transverse compartments (from lumen to the mucosa). 

The variations in the gut microbiota composition, within and between individuals, in combination with the fact that the primary sample (stool) is only representative of the overall colonic content, limit our ability to define a ‘healthy’ gut microbiota. This makes the whole gut microbiota management/modulation concept extremely tricky because your ‘healthy’ gut microbiota might not be healthy in another context. 

Nevertheless, any impairment of the gut microbiota, for example, by administration of oral antibiotics or lifestyle choices, affects the functionality of our local defence systems. At the same time, any malfunction of the epithelium, the mucosal immune cells or the ENS, affects the microbiota composition, diversity and functionality. Especially, the GI barrier, and consequently gut health, are directly altered not only by local disturbances but also by any systemic burden. A normal GI microbiota of rich diversity, and more importantly an intact GI barrier that counteracts and cooperates with the existing/commensal microbiota, are thus needed to maintain gut health. 

The consequences of such interactions are only just beginning to be understood. The gut mucosal immune system both controls the GI microbiota and depends on it, as the continuous challenge of microbial antigens to the mucosal immune system is required for its normal development and function. To this end, it is not surprising that the GI immune system contains cells capable of recognising microbial antigens, by specific receptors that form the basis of the communication between the GI microbiota and the GI immune system. This way any danger from pathogens can be quickly recognised and dealt with, while at the same time the friendly coexistence between us and our microbes is maintained. Under normal conditions, those mechanisms allow regulation of inflammatory responses to harmless antigens, such as food antigens or microbial antigens derived from friendly commensals, to achieve and maintain mucosal tolerance. 

Therefore, our protection and maintenance of gut health is dependent on the ability of the GI immune system to regulate the complex balance between the defence against, and the acceptance of our gut microbiota.

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