Should we trust our guts?

Almost daily there seems to be a new study linking the gut microbiota to a different health outcome or disease. Prolonged consumption of emulsifiers has been linked to an increased abundance of pro-inflammatory bacteria.

The presence of uric acid consuming bacteria in the microbiota may be protective against gout. The avoidance of gluten in non-coeliac populations has been linked to a lower abundance of beneficial bacteria species. Given their well-established importance, should health professionals be encouraging patients to have their microbiota tested to help diagnose and manage health conditions?

What is the Microbiota?

The microbiota and microbiome are two terms that are often confused. The microbiota refers to the diverse collection of microbes that reside in the gastrointestinal tract, which includes bacteria, archaea, fungi, microbial eukaryotes, and viruses. The microbiome encompasses the microbiota in addition to their genes and the environmental factors that influence them. Within the gastrointestinal tract of a healthy adult, researchers have only identified two dominant bacterial phyla, Firmicutes and Bacteroidetes, along with an additional four phyla that are represented in lower concentrations: Actinobacteria, Proteobacteria, Verrucomicrobia, and Euryarchaeota.

The Gut Microbiota and Health

A healthy gut microbiota plays a crucial role in maintaining health, influencing immune function, mental health, and digestion. One of the most well-understood and important functions of the gut microbiota is their ability to ferment non-digestible dietary fibres. This fermentation process results in the production of beneficial microbial metabolites, such as the short chain fatty acid butyrate, an anti-inflammatory metabolite known to inhibit the production of cytokines. While the precise strains with this capability have not been identified, it is believed that most bacteria in the phylum Firmicutes are butyrate producing. As such, it could be hypothesized that an abundance of these bacteria may be protective against inflammatory disease states.

Yet what constitutes the composition of a ‘healthy gut microbiome’ is yet to be explicitly defined, and the evidence that is currently available suggests that microbial diversity is the most reliable indicator of a healthy microbiome. Microbial diversity is a measure of how many different species are present and how evenly they are distributed.

The Gut Microbiota and Disease

Low microbial diversity and a depletion of short chain fatty acid-producing bacteria are considered common features of dysbiosis. This state of dysbiosis can induce negative effects like inflammation or infection, which have been linked to various disease states.

Current Methods for Testing Microbial Diversity

The composition of gut microbiota is commonly quantified using DNA-based methods such as next-generation sequencing of 16S ribosomal RNA genes and whole genome shotgun sequencing. 16S rRNA gene sequencing is the most widely used throughout the literature. The 16S rRNA gene is a reliable marker for identifying bacteria since it is ubiquitous to members of this domain. However, this sequencing method is limited to genus-level resolution and is unable to identify microbial functions. On the contrary, shotgun sequencing offers strain-level resolution for all microorganisms present within a given sample. In addition, shotgun sequencing can give insight into potential microbiota functions. Given the greater specificity of this method, it is becoming more widely used.

What Can These Tests Tell Patients About Their Health

Existing microbiome tests focus on taxonomy, with a one-time test able to provide patients with an indication of their overall microbial health, delivering a snapshot of the specific types and overall diversity of microbes that are present in the stool at the time of testing. Routine testing can also show the effect that illnesses, dietary changes, and medications can have on the microbiome.

Yet, the vast majority of microbes that reside in the human gut remain unknown, and unfortunately, these tests are not yet able to accurately identify the functions of the microbiota that are present. Ultimately, these tests cannot diagnose health conditions.

The microbiome is incredibly complex. It is unlikely that there is one ideal microbiome that is indicative of good health; instead, it is more likely that there are several different species of microbiota that are able to produce the same metabolites, meaning it is highly probable that there are many different representations of a healthy microbiome.

This isn’t to say patients should be discouraged from having their microbial composition tested, but we are still years away from incorporating microbiome testing into regular health checks. Health professionals should do their best to ensure patients have realistic expectations when it comes to microbiome testing.

The Potential of Faecal Microbiome Transplants (FMT)

As our understanding of the human microbiome deepens, faecal microbiome transplants (FMTs) have emerged as a potentially revolutionising treatment approach. FMT is defined as the infusion in the colon of faeces from a healthy donor to a recipient with presumed gut dysbiosis. This procedure has been effective in treating Clostridium difficile infection and is now routinely used for this purpose.

While FMTs are not yet clinical practice for any other conditions, they are still being explored. For example, researchers have been able to demonstrate that body composition and metabolic phenotypes are transmissible through FMTs. In one frequently referenced study, researchers transplanted faeces from human adult twins, in which one was obese and the other lean, into germ-free mice. After feeding the mice the same calorie-controlled diet, it was found that the mice who were colonised with the obese twin’s gut microbiota became obese themselves, while the mice who received the transplant from the lean twin remained lean. Animal models such as this are helping to guide a new era of innovation in microbiome therapeutics.

Current Recommendations for Improving Microbial Diversity

While we are not yet able to recommend precise tools that will target specific microbiota to treat different diseases, we do know that dietary interventions are the most powerful influence on the gut microbiome. For patients wanting to improve their microbial diversity, the following simplified recommendations can be made:

1) Consume 30 different fibre-rich plant-based foods each week.

2) Consume regular small amounts of fermented foods, such as milk, cheese and yoghurt, kimchi, sauerkraut, miso and tempeh.

3) Limit the consumption of processed and ultra-processed foods.

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