A Gut Feeling: The Microbiome and Scleroderma

At the 2021 SRUK Virtual Conference Dr Elizabeth Volkmann presented a very popular session on Understanding Gastrointestinal Involvement in Scleroderma – where she introduced the concept of how a person’s microbiome might influence their condition. This article takes a deeper dive into the world of the microbiome.

Human Is?

If you ask a scientist how many cells make up the average human body, it is unlikely that you will get a straight answer. Unlike jellybeans in a jar, human cells are non-uniform, differing in their size, volume, shape and function. Best estimates say that there are around 37 trillion body cells in the ‘average’ human body. Here’s where it gets surprising though:  we are more non-human than human.

Our microbiota, the microorganisms which include the bacteria and fungi which live on our skin, and our mucosal surfaces like the intestines, oral and nasal cavities and our reproductive tracts can outnumber our body cells by more than two-fold, making us less human than we think!

But what is the role of these microbial colonisers? How do they influence our health and well-being? Do they play an active role in the development or worsening of autoimmune conditions such as scleroderma? Or are they merely witnesses, offering testimony to the changes going on in our bodies?

Your Microbiota, the Microbiome and you

The term microbiome was first coined in 2001 and encompasses the resident microbial species found within a person and the molecules that these microbes produce.  Over the past decade interest in this area of research has exploded, with the microbiome implicated in everything from digestive to mental health. This is however an older fascination, with the first work into the microbiome and the differences between the microorganisms found in different locations on the human body carried out by the father of microbiology, a Dutch draper named Antonie Van Leewenhoek in the 1680s.

Our microbiome is a vital part of what makes us ‘human’ and fulfils many useful functional roles within our bodies; like helping to digest certain foods, like sugars in human breast milk which are otherwise indigestible by babies, preventing disease-causing bacteria from colonizing our bodies and helping with the development and regulation of our immune systems.

Since the days of Van Leewenhoek, science has moved on and we now understand that a person’s microbiome alters throughout their life course due to age and that the microbiome can vary from person to person due to factors like where we live and the foods we consume. 

The Microbiome in Autoimmunity

Autoimmune conditions are complex, many factors may combine to cause a person to develop an autoimmune disease. These include environmental factors such as diet, or exposure to certain chemicals – which can include medications. There are also specific factors unique to the individual like their genetic makeup and their immune response. The responsiveness of autoimmune conditions to these factors makes it tempting to suggest that there may be a role for the microbiome in either the initiation or exacerbation of autoimmunity.

Research into this topic began with autoimmune conditions affecting the gut, such as Crohn’s diseases and ulcerative colitis. The balance of gut microbes was examined, revealing that people living with these conditions have reduced microbial diversity and increased outgrowth of certain bacterial species in their intestines, when compared to ‘healthy’ controls. From these early beginnings, the gut microbiome has been studied in other conditions including lupus, rheumatoid arthritis and multiple sclerosis.  

The Microbiome and Systemic Sclerosis

Systemic sclerosis is a complex condition, around 90% of those living with it will experience gastro-intestinal symptoms over the course of their illness. Scientists began to study the microbiome in gut involvement in systemic sclerosis studying both patient stools and ‘washings’ taken from two regions of the large intestine from both patients and healthy controls. Those living with systemic sclerosis were found to have decreased levels of commensal or ‘good’ bacteria, and increased levels of ‘bad’ bacteria compared to healthy controls. Patients who were experiencing severe to moderate gastrointestinal symptoms were shown to have increased levels of two other types of bad bacteria; compared to those with mild or no symptoms.

Perhaps more surprisingly research has extended into the gut microbiome in the case of other manifestations of scleroderma such as interstitial lung disease (ILD). With differences being observed in the gut microbial make up in patients with and without ILD.

Cause or effect?

The significance of this research is still up for debate. Changes in the gut microbiome may not be an initiating or contributing factor to the development of or worsening of autoimmune diseases. Instead, these changes may be occurring in response to the inflammatory changes happening in a patient’s body. The studies carried out to date have been relatively small and larger research consortium led projects are needed to increase our understanding of the significance of these data perhaps studying people at different stages of scleroderma.

Functional studies, using special mice known as germ free mice, bred and housed in sterile conditions to be completely devoid of any bacteria including ‘friendly’ bacteria could help determine the mechanisms by which gut microbes influence scleroderma. Functional studies have provided information in mouse models of multiple sclerosis where the transplantation of stool samples from patients with MS resulted in worse MS-like symptoms in mice compared to from healthy members of the same household.

How could we use this information to improve scleroderma?

If these gut microbial changes are proven to be contributing to the inflammation and other symptoms in people with scleroderma, then there is the exciting possibility that clinicians could intervene to redress any microbial imbalances, potentially reducing inflammation or preventing certain aspects of the condition developing.

Theoretically, this could be achieved by providing patients with specialized blends of probiotics. If possible, such an add-on treatment would be significantly easier to offer both logistically and in terms of cost, signifying a real turning point in the therapy options for scleroderma. Much more research is required before we can start getting excited, but who knows? Perhaps tweaking the bacteria living within your gut could be the next accepted therapeutic strategy for treating scleroderma!