Imagine waking up one day with fingers so stiff you can't button your shirt. Or a face so tight you can barely smile. Or worse, imagine the fear and uncertainty of living with a disease that slowly, relentlessly, and silently attacks your vital organs – from your heart and lungs to your digestive system.

This is the scary and devastating reality for people living with a complicated and rare condition known as systemic sclerosis. And while we might not have all the answers when it comes to this devastating disease, recent research has turned up some potentially promising insight. As it turns out, the secret to understanding this confounding condition might just lie in a tiny compound produced in your gut known as trimethylamine N-oxide.

In this blog post, we’ll explore the intricate and complex connection between the two. So let's start by defining exactly what systemic sclerosis is. 

What Is Systemic Sclerosis (Scleroderma)?

Systemic sclerosis, also known as scleroderma, is a rare autoimmune condition – meaning the immune system mistakenly attacks your own healthy tissues. In the case of systemic sclerosis, the immune system targets the connective tissues found in your skin, blood vessels, and internal organs – leading to fibrosis, excessive collagen production, and tissue damage. In fact, the name “scleroderma” comes from the Greek words “sclero” (hard) and “derma” (skin), which describe one of the disease's prominent features – the hardening and thickening of the skin.

Some of the hallmark symptoms of systemic sclerosis can include:^1,2,3

• Skin involvement: The most visible symptom of systemic sclerosis is skin involvement – leading to skin thickening, tightness, discoloration, and a shiny appearance. In some cases, skin may also develop ulcers or sores – especially during cold weather.
• Raynaud's phenomenon: Many individuals with systemic sclerosis experience what; ‘s known as Raynaud's phenomenon – spasms in the small blood vessels which cause fingers and toes to turn white or blue and lead to numbness, pain, and tissue damage.
• Internal organ involvement: One of the most concerning aspects of systemic sclerosis is its potential to affect internal organs which can lead to more serious complications, such as:
  • Interstitial lung disease: Scarring of the lung tissue that can result in breathing difficulties.
  • Pulmonary hypertension: Elevated blood pressure in the lungs that can strain the heart.
  • Gastrointestinal issues: Problems with swallowing, acid reflux, and intestinal motility are common.
  • Heart involvement: Inflammation of the heart and its blood vessels can occur.
  • Kidney problems: Damage to the kidneys may lead to hypertension and kidney failure.

So what on earth causes this perplexing and frightening condition?

What Causes Systemic Sclerosis?

The exact cause of systemic sclerosis (scleroderma) is not fully understood, but it is believed to result from a combination of factors such as:^4,5

• Immune dysfunction: Dysregulation of the immune system can essentially confuse your body’s defenses – causing your immune cells to mistakenly attack your own healthy connective tissues.
• Genetics: There is evidence to suggest a genetic predisposition to systemic sclerosis and certain genes have been identified as potential risk factors for the disease – but it is not solely determined by genetics.
• Environmental triggers: Environmental factors can play a pivotal role in triggering autoimmunity – especially in genetically susceptible individuals. These triggers may include exposure to certain toxins, infections, or other environmental factors. 
• Vascular abnormalities: Some research suggests that abnormalities in the blood vessels, including abnormal narrowing of the small blood vessels in response to cold or stress, may contribute to the development of systemic sclerosis. These vascular changes can precede other symptoms of the disease.
• Hormonal factors: Hormonal factors, including estrogen, may influence the development and progression of systemic sclerosis. The disease is more common in women than in men, and hormonal changes, such as those occurring during pregnancy or menopause, can sometimes affect its course.

The true underlying causes of systemic sclerosis are complex and not fully understood. But it’s likely that there are numerous factors that all come together to set the stage for the development of this mysterious condition. But there’s another underlying factor that might bring us one step closer to understanding the root cause of systemic sclerosis – your gut microbiome.

What Is the Gut Microbiome?

The gut microbiome is a complex and diverse community of microorganisms that resides within your gastrointestinal tract – primarily in your colon and small intestine. Your microbiome is integral to your health – with this complex ecosystem of bacteria, viruses, fungi, and other microbes working in harmony with your own cells in various ways.

One of the many ways in which these microbes impact how our own cells operate is via the production of a variety of compounds known as metabolites. You see, as the microbes in your gut digest food and carry out their day-to-day functions, they release different molecules that then interact with your own cells. Many of these metabolites are incredibly helpful and even essential for our well-being. 

But sometimes, if the delicate balance of your gut microbiome becomes disrupted, you can have an overgrowth of certain bacteria – and subsequently have an influx of specific metabolites. And one such metabolite that can get thrown out of whack is a little molecule known as trimethylamine N-oxide.

What Is Trimethylamine N-Oxide (TMAO)?

Trimethylamine N-oxide is a little compound that’s formed through a process that goes like this:^6,7

• Dietary intake: TMAO production begins with the consumption of certain nutrients in the diet – namely compounds like choline, phosphatidylcholine, and carnitine, which are found in various foods like red meat, fish, eggs, and dairy products.
• Gut microbial metabolism: After these dietary compounds are ingested, they enter the digestive system and reach the colon, where the majority of gut bacteria reside. Certain types of gut bacteria (like fusobacterium, desulfovibrio, ruminococcus species) break down choline, phosphatidylcholine, or carnitine into what’s known as trimethylamine (TMA) through a process known as fermentation.
• Trimethylamine (TMA) conversion: TMA is transported via the bloodstream to the liver where it’s further broken down and converted into trimethylamine N-oxide (TMAO).
• Circulation and elimination: TMAO can then travel throughout the body via the bloodstream until it is eventually eliminated through the kidneys and ultimately, your urine.

Now TMAO is not necessarily problematic in and of itself when levels are balanced. But if TMAO levels rise, it can become toxic and lead to a number of health concerns. And that list of health concerns may just be growing a little longer – as new studies have revealed that this tiny metabolite might just be linked to systemic sclerosis.

The Link Between Systemic Sclerosis and TMAO

Recent studies have uncovered that there may be a direct link between TMAO levels and the development of systemic sclerosis – with higher concentrations of TMAO consistently found in individuals with this complex disorder. While more time and research and needed to truly understand the connection, it’s speculated that increased circulating TMAO levels may contribute to the development and progression of systemic sclerosis via a process that goes something like this:^8,9

• Inflammation of the endothelium: Your endothelium is a continuous, thin layer of specialized cells known as endothelial cells. These cells line the interior surface of blood vessels – serving as a barrier between the bloodstream and the surrounding tissues. Increased TMAO levels can incite inflammation within your endothelium.
• Endothelial injury: Prolonged inflammation incited by elevated TMAO levels can lead to oxidative stress and permanent damage to this layer of endothelial cells.
• Profibrotic cytokine signaling and collagen deposition: As endothelial cells become damaged, specific signaling pathways are activated by cytokines (cell-signaling molecules that mediate communication with your immune system). Once activated, these pathways promote fibrosis and the deposition of collagen – spurring the formation of excess fibrous connective tissue.
• Suppression of artery dilation and inhibition of nitric oxide release: Your epithelium plays an important role in blood flow by modulating the relaxation or dilation of arteries and the release of dilation-promoting molecules like nitric oxide. Endothelial injury triggered by elevated TMAO can impair this process and reduce the flow of oxygen and vital nutrients – further exacerbating injury to the endothelium.
• Differentiation of fibroblasts into myofibroblasts: Increased concentration of TMAO can also spur the cellular process in which cells known as fibroblasts undergo transformation into myofibroblast cells. Myofibroblasts are central players in the fibrotic process and one of the hallmarks of systemic sclerosis.

While these findings might bring us one step closer to learning how to better manage and prevent this life-altering disease, more time and research are needed to truly inderstand the role TMAO might play in systemic sclerosis. But one thing we can certainly take away from these findings, is the importance of gut health.

How Can I Lower My TMAO Levels and Support Gut Health?

The gut truly is the gateway to health, with your gut and your microbiome having a monumental impact on every facet of your well-being. So whether you have systemic sclerosis, are battling another ongoing diagnosis, or simply want to bolster your defenses against developing a chronic condition, here are some steps you can take to keep TMAO levels in check and support a healthy gut:

• Balance your consumption of foods rich in choline and carnitine, such as red meat, processed meat, and certain dairy products
• Increase your intake of foods with lower TMAO precursor content – like vegetables, fruits, whole grains, and plant-based proteins
• Stay hydrated as adequate hydration can help support kidney function – potentially aiding in the excretion of TMAO and its precursors from the body
• Inoculate your gut with beneficial bacteria by incorporating Probiotics and Spore-Based Probiotics
• Bolster your gut barrier lining with nutrients found in things like Collagen Boost and Gut Shield
• Manage stress and get plenty of rest as your sleep patterns and mental health can have a major impact on gut health

To dive deeper into how you can keep your gut happy and healthy, head over and read my article all about healing your gut. Or head over and browse through all of my favorite gut-boosting supplements on my online store.

When It Comes to Your Health, You Are Your Own Best Advocate

While we still have a ways to go when it comes to truly understanding this complex condition, these findings that link gut health to systemic sclerosis are promising. But one thing that findings like these underscore is that when it comes to your health, you are your own best advocate. Your daily choices about how you eat, move, sleep, and think are hands down your most powerful weapons against any disease – systemic sclerosis included.

If you’re looking for more ways to really solidify your foundation of health by making the very best day-to-day choices for your unique circumstances, I’ve got you covered. My blog and YouTube channel are chock full of resources to help empower you with the knowledge and tools you need to advocate for your own wellbeing. And I drop new content each week, so be sure to sign up for my email list so you don't miss a thing (just input your name and email at the bottom of this page).

But true healing and vibrant health don’t just come from the physical changes – you have to take a holistic, mind, body,and soul approach. So if you need some help tapping into that inner healing and prioritizing your mental, emotional, and spiritual health too – you’ve got to check out my new book Unexpected: Finding Resilience Through Functional Medicine, Science, and Faith. In it, I peel back the layers of my personal journey and give you access to the exact roadmap I used to transform my health, happiness, and purpose to create a life more beautiful and fulfilling than I could have imagined. Click here to grab your copy today.

Resources:

1. Scleroderma – Symptoms and causes – Mayo Clinic
2. Systemic Sclerosis – StatPearls – NCBI Bookshelf (nih.gov)
3. Systemic scleroderma: MedlinePlus Genetics
4. Scleroderma – Symptoms and causes – Mayo Clinic
5. What Is Scleroderma? Symptoms & Causes| NIAMS (nih.gov)
6. Trimethylamine N-Oxide: The Good, the Bad and the Unknown – PMC (nih.gov)
7. Trimethylamine N-oxide (TMAO) in human health – PMC (nih.gov)
8. JIR_A_409489 1895..1904 (dovepress.com)
9. Metaorganismal TMAO pathway driving scleroderma pathogenesis: novel gene-environment interaction paradigm and therapeutic target – John Varga (grantome.com)