03/03/2019

The Gut Microbiome and Health

The Gut Microbiome and Health

The microorganisms that call our gut home have been the focus of a lot of attention in recent years. Some big headlines have claimed that the gut microbiota has a role to play in everything from digestive problems to weight loss, depression and anxiety, and even autism. But in order to pick apart these headlines, it’s crucial to understand what we know about the human gut and its resident microbes …and just as importantly, what we don’t!

Firstly, it’s useful to define some of the commonly used terms (1):

  • Microbe or microorganism: a type of microscopic, usually single-celled organism. There are many different types including bacteria, some types of fungi, archaea, protozoa and algae. Although viruses are not cellular and it’s even debatable whether they are alive at all, they are often considered a microbe.
  • Microbiota: a collection of microbes found within a specific environment e.g. the gut
  • Microbiome: all of the types of microbiota, their genes, and the specific environment in which they are found
  • Symbiosis: a close relationship between two species
  • Parasitism vs mutualism: a parasite causes damage to its host, whereas both species benefit in a mutualistic relationship. The third type of relationship exists where one species benefits while the other is neither harmed nor benefited, referred to as commensalism
  • Metabolite: the products of metabolic reactions within cells

With these definitions under our belts, it’s easier to understand what is meant by the “human gut microbiome”: the collection of symbiotic microbes and their genes that live in the human gut. Most research into the microbiome has focussed on bacteria only, so there is still a lot we don’t know about the other organisms and how they interact with each other, let alone us. But where do these microbes come from?

Establishing a Microbiome

Initially, we are colonised by microorganisms during birth, forming the basis of our early microbiome (2). These quickly multiply until the number of bacterial cells roughly equal the number of human cells (previous claims that bacteria outnumber human cells by 10:1 have since been disproved(3)). It has been found that the way a baby is delivered (i.e. vaginally or via caesarean) has a big effect on the diversity and types of microorganisms that initially colonise the gut. Children born vaginally appear to have a greater diversity of bacterial species, and higher proportions of Bifidobacteria species(4). Although the delivery method is important very early in a child’s life, after about 6 months of age most children acquire high numbers of Bifidobacteria. Babies who are premature or born by caesarean seem to achieve similar microbiota, but slightly later than full-term vaginally delivered babies. After the initial colonisation, the development of the gut microbiome is highly dynamic and responds to many factors including life stage, local environment, diet, lifestyle, the presence of disease and medications, especially antibiotics.

What exactly these microbes do and whether they are parasitic (harmful), mutualistic (beneficial) or commensal (neither) is a simple question to ask but not so simple to answer. We are only scratching the surface of all of the activities of our microbiota, and how they interact with us.

Functions

One of the major effects the gut microbiota has on its host is to help the immune system develop(5). The gut presents a major potential route of infection, as it comes into contact with food and other components of our environment. Risk of infection is managed by the gut having its own localised immune system. The gut microbiota interacts with the local immune system with “good” species helping it to develop and enable it to identify species that could cause infection. It is also important for the gut’s immune system to properly recognise food, and not mistake components from food as invaders. If the immune system inappropriately responds to certain types of food, this can result in symptoms of food allergy. There are many factors that determine whether a person is likely to suffer from a food allergy, and although the gut microbiome is a possible factor for some people(6), current research has yet to prove a concrete relationship with the gut microbiota.

Besides immunity, the evidence is mounting to show that microorganisms can have much farther reaching effects on health. There is growing recognition that a large number of metabolites they produce are absorbed and have effects on the host. Some metabolites interact with different organs such as liver or kidney cells and others even cross the blood-brain barrier. Examples of this include the short chain fatty acids: acetate, butyrate and propionate. Some types of dietary fibre that we cannot digest are transported to the bowel where the bacteria get to work. The end result of bacteria fermenting these fibres include these fatty acids which can be used as an energy source by gut cells, control colonic pH levels, and influence appetite regulation and energy homeostasis(7).

A “Healthy” Gut Microbiome

Many studies have now described a “healthy” gut microbiome, collectively including over 1000 identified bacterial species. Each person, however, is likely to carry only around 160 species, dominated by species belonging to two groups: Bacteroidetes and Firmicutes(5). Although they account for a majority of the species found in the gut, the ratio between these two groups varies significantly from person to person. As such the concept of “healthy” is harder to define when applied to gut microbial populations. A better measure of “healthiness” has been developed: the functionality of the microbiome.

Each bacterial species contains a specific set of genes, which enables it to perform certain metabolic functions. In many cases, different bacteria species will contain similar or identical genes that enable them to fulfil a similar role(8). For example, if a bacteria has the genes that enable it to digest a particular kind of dietary fibre present in the host diet, it could colonise the host’s gut, but so could another species with the same genes. So long as a person has a range of bacterial species that fulfil all the core functions, that microbiome can be considered “healthy”. Crucially although the core functions may be met, not all species are equally efficient at the same tasks, and differences in effectiveness between species may account for differences in host well-being (9).

Conditions Associated with Gut Microbiota Changes

Irritable Bowel Syndrome (IBS) is a functional gut disorder characterised by abdominal pain or discomfort in conjunction with altered bowel habit (diarrhoea, constipation, or alternating), frequently associated with feelings of bloating and flatulence. Many studies have suggested changes in gut microbiota are associated with the condition, though there is not a broad consensus on the alterations. Some reported changes including the reduction in species diversity, change in relative proportions of aerobic to anaerobic species, greater variation over time, and more abundant bacteria living in close contact with the gut lining. There is evidence that these changes are associated with gut immune system activation, changes in intestinal transit, and effects on the nervous system including sensitivity to pain(10).

Inflammatory Bowel Disease (IBD) is a chronic and episodic auto-immune condition of the digestive tract. It is sub-classified into Crohn’s Disease, which can affect any part of the digestive tract and Ulcerative Colitis, which mainly affects the large bowel. The most consistent findings with relation to changes in the gut microbiota in IBD are a) reduced diversity, b) a decrease in Firmicutes and c) an increase in Proteobacteria(11). It is possible that these changes in a genetically susceptible person will result in a heightened immune response, although whether the changes are the result of inflammation or the cause is not entirely clear.

Obesity, diabetes and cardiovascular disease are all associated with chronic low-grade inflammation(12). The gut microbiota can affect systemic inflammation as well as local gut inflammation. In addition, they have been shown to affect the amount of energy released from food, the rate of fat accumulation, and ability to control blood glucose levels. Several studies have suggested that changes in the ratio of Firmicutes and Bacteroidetes species are correlated with obesity even when similar diets are eaten(13), though other studies failed to find the same effect.

Changes in the gut microbiota have been proposed in other conditions including colorectal cancer, liver disease, depression and anxiety and autism, and research is ongoing.

Modifying the Gut Microbiome

Changes in the species or activity of gut microorganisms are thought to play a role in many health conditions, though often the mechanisms are not very clear. In tandem with this work, a significant amount of research is taking place to see whether modifying gut bacteria could improve health. Antibiotics are an obvious way to alter the gut bacteria, however, they will also affect “good” bacteria, so the end result is often negative.

Aside from antibiotics, probably the most rapid and profound effect we can have on our gut microbiota is through diet. A landmark study has now shown that dietary changes can significantly alter gut microbial composition and activity within a matter of days(14). For example, an increase in dietary fat is associated with bacterial species that can tolerate high amounts of bile acids, which are released in response to fat intake. Conversely, high fibre intake is associated with increased abundance of Prevotella species and short chain fatty acids. High intakes of protein are associated with species that can ferment amino acids (such as Bacteroides species) and the end products of this fermentation(14).

Other methods to alter the gut microbiota have proved effective but on a less pronounced scale. Probiotics involve providing live microbes in high amounts that are thought to provide a health benefit. In order for a probiotic to be effective, it must be taken regularly to maintain levels of the microorganism. Most studies have focussed on a range of sub-species and strains belonging to the Lactobacillus, Bifidobacteria, Enterococci and Streptococci species. Reviews of probiotic research have shown a large number of poorly conducted trials, but well-conducted trials of probiotics appear to improve symptoms in IBS(15). Many probiotic preparations sold are of poor quality, however, and it is important to check the precise strain and active dose and whether it is effective before considering taking a probiotic.

Prebiotics, on the other hand, are the provision of specific substrates that can be used by bacteria already within the gut. The aim is to promote the growth of specific species thought to be beneficial to health. They are usually forms of dietary fibre that cannot be digested by the host, for example, inulin and fructo- and galacto-oligosaccharides (FOS and GOS). There is less published research for prebiotics than for probiotics, and some have proven effects on the gut microbiota, particularly inulin and FOS which stimulate Bifidobacteria growth(16). The downstream health benefits of this have been harder to establish. A combined live probiotic bacteria and prebiotic fibre are referred to as a synbiotic and careful pairings could improve the overall efficacy.

Summary

The gut microbiota are an important biologically active component of their human host. Equally, they can be affected by the health of the host and a two-way relationship is evident. Our ability to analyse the organisms living in our digestive tract is relatively recent, and our ability to assess their functionality more so. It is highly probable that alterations in the gut microbiome are associated with changes in human health, but the relationship is highly complex. As more research is undertaken, it may be possible to effectively modulate the species and activities of bacteria, archaea, fungi and viruses to optimise health and manage disease.

 

References

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