Over the last few decades we've learnt how important the trillions of bugs that live inside us are to our overall health.
Our gut microbiome — the ecosystem of microorganisms including bacteria that inhabit our intestinal tract — not only assist with digestion, they also have a profound impact on our immune system and metabolic health.
Lifestyle factors, such as eating a lot of junk food or taking antibiotics, can negatively impact this ecosystem.
This disruption — known as dysbiosis — is thought to contribute to the rise of autoimmune diseases, particularly in Western societies.
Now researchers are hoping to use our improved knowledge of how the gut microbiome works to help come up with new treatments, and potentially even cures, for autoimmune diseases.
What makes a healthy microbiome?
Our diets not only nourish us, but are also the main source of nutrients for our gut bacteria.
So, it's not surprising that diet is a key factor that influences the make-up of bugs in our gut, collectively known as our gut microbiota; and what they're able to do for us, or their function.
Gut bacteria use complex carbohydrates as one of their main sources of energy. Complex carbohydrates, like dietary fibre, are found in high quantities in foods such as vegetables, oats, legumes and many fruits.
Mammals like humans do not possess the enzymes required to digest dietary fibre, allowing it to escape to the large intestine, where it feeds our gut microbes.
The major issue in recent decades is that society has transitioned to consuming more foods that are highly processed, which are high in fats and simple sugars, and most importantly, low in dietary fibre.
For example, the average American consumes 10 to 15 grams of dietary fibre a day, which is much less than the recommended daily intake of 25g for women and 38g for men.
As a result, many beneficial microbes that rely on dietary fibre as a food source starve and are outcompeted by other bacteria that don't.
For example, the gut microbiota of children from Europe was completely lacking bacteria from the genera Prevotella and Xylanibacter, while it was high in children from a rural African village in Burkina Faso.
These bacteria are known degraders of dietary fibre, suggesting that not eating enough dietary fibre may wipe out these beneficial bacteria from our gut.
Various studies have found a reduction in Prevotella in patients with multiple sclerosis (MS), suggesting a link between fibre intake, specific gut bacteria and the disease.
On the contrary, taking dietary fibre supplements like inulin led to an increase in gut bacteria that are considered beneficial, like Bifidobacterium and Anaerostipes.
How does the microbiome benefit us?
As our gut bacteria degrade dietary fibre they release byproducts known as metabolites.
These metabolites include short-chain fatty acids such as acetate, butyrate and propionate.
Butyrate is the main food source for gut epithelial cells, the cells lining our intestinal tract, and also help prevent the expansion of "bad bugs" in the gut.
Acetate can be a food source for immune cells such as regulatory B cells, an important subset that limit the severity of rheumatoid arthritis.
Short-chain fatty acids have also been shown to help maintain healthy gut barrier function.
Otherwise if our gut is too leaky, microbes and bacterial components like lipopolysaccharide can leak into our bloodstream and induce inflammation all around the body.
This phenomenon, known as leaky gut syndrome, has been proposed as one factor causing autoimmune disorders.
For example, patients with lupus had higher levels of blood lipopolysaccharide. Likewise, increased gut permeability and circulating lipopolysaccharide has been found in patients with rheumatoid arthritis.
Intriguingly, mammals including humans have evolved receptors to sense the metabolites produced by our gut microbes.
When these receptors are activated, it often triggers an anti-inflammatory immune response and is also linked to our body producing more anti-inflammatory regulatory T cells.
Regulatory T cells are immunosuppressive immune cells critical for controlling inflammation, and in autoimmunity they are crucial in stopping our immune system from attacking our own body.
A reduction in regulatory T cells or their function is a hallmark of almost all autoimmune diseases.
Increasing the number of regulatory T cells and improving gut barrier function was associated with better outcomes in a preclinical model of MS.
Short-chain fatty acids are just one of the many metabolites produced by the gut microbiota.
Other compounds, such as those deriving from microbial metabolism of the amino acid tryptophan, were also found to be important in autoimmune diseases.
These metabolites were found to be lower in individuals with MS, and in preclinical models, they were found to suppress inflammation in the central nervous system underlying the disease.
Improving our gut microbiome
Researchers are looking at ways to improve our gut microbiota to reap more of its benefits, both for general health and for people living with autoimmune diseases.
Probiotics — which involve consuming one or more strains of live bacteria — are commonly touted as a way to optimise our gut microbiota and the market for them alone was estimated to be worth $US87.7 billion in 2023.
But numerous studies have shown that most probiotics do not colonise our intestinal tract, have little or no impact on our gut microbiota composition, and are often excreted shortly after consumption.
The use of probiotics for the remission of autoimmune diseases like ulcerative colitis shows promise, however its impact on other autoimmune diseases is inconclusive.
This complexity also applies to other strategies designed to modify our gut microbiota, such as prebiotics, which aims to promote the growth and activity of specific bacteria.
The effectiveness of prebiotics largely depends on an individual's existing gut microbiome, their genetics as well as their overall diet.
There is also limited scope for prebiotics to rebalance the gut microbiota, as they usually target specific groups of bacteria like Bifidobacteria.
There are other strategies, like postbiotics, which involve the direct administration of microbial products. However, research on its use in humans as well as its effectiveness is even more poorly defined.
Faecal microbiota transplants have been incredibly successful for the treatment of Clostridium difficile infections, but their application in autoimmune and other diseases remain to be investigated.
The future of our gut microbiome and autoimmune diseases
It is evident that our gut microbiome plays an integral role in our overall health.
Specific gut microbiota signatures, such as the increase or decrease of certain species, have been identified in various autoimmune disorders, however not always consistently across different studies.
We still do not fully understand whether many of the observed changes in the microbiome are a cause or consequence of the disease, or a combination of both.
It's unlikely that there will ever be a simple definition of what exactly makes up a healthy or a dysbiotic gut microbiome.
Different gut microbiota compositions can perform similar functions and variations in microbiota composition do not necessarily reflect differences in the health of the respective hosts.
Indeed, aiming to restore or improve health by changing the composition of our gut microbiota may be misguided. Instead we may be better served by adopting long-term habits that underlie microbiome health, such as consuming diets high in dietary fibre.
There may be specific diseases or scenarios where manipulating our microbiota may be a viable strategy, whereas for other diseases the microbiome may only play a small role.
In those cases, manipulating your microbiota should be viewed as part of a broader, holistic approach to disease management.
Regardless of impact, it's likely that any attempts to alter our microbiota will require a personalised approach, where information about our microbiome — its composition, diversity and function — will need to be reconciled with genetics and other lifestyle factors — for example, diet, exercise, smoking status — to inform the most appropriate strategy.
Dr Jian Tan is a postdoctoral research fellow with the Charles Perkins Centre at The University of Sydney. He leads a research program examining the relationship between the gut microbiome and the immune system.
