The Gut – Skin Axis: Overwhelming evidence of the relationship between gut dysbiosis and skin conditions

An infinite number of evidence suggests the involvement of gut microbiome in human skin diseases. Dysbiosis in the gut alters the microbiome of the skin leading to wide variety of skin conditions including dermatitis, psoriasis, acne vulgaris, and skin cancer. Altered gut microbiome is associated with an altered immune system, promoting the development of skin conditions. This article aims to provide evidence on the dietary links, hygiene, gut microbiome, and immune response in skin pathologies. The communication between the gut and skin (other organs as well) is bidirectional, both have the mechanism to send and receive signals from one another.

What role they play in our health?

Separating the inside from the ouside

The skin is the first-line barrier from the outer environment, protecting us from harmful substances. Its total surface of 25 m² is one of the largest epithelial surface. It is continuously interacting with microbes from the outside. On the other hand, the gastrointestinal tract accounts for about 30 m2 of total surface which also aims to separate the host from its outer environment. The GI tract is a tube which is about 5m in length. The GI tract acts like a processing plant – we bring food (steak, potato, vegetables) from the external environment to the inside of the body; the GI tract turns complex food into small molecules to be used by the body as fuel (amino acids, simple sugar); these molecules will be transported to the organs and tissues via bloodstream. Imagine that we take in about 1-2 liters of food (solid, liquid) in a typical meal. As it passes through the GI tract, 7 liters of secretion will be added (enzymes, buffers, acids). Reaching the small intestine, we already have about 9 liters of fluids to pass through, which shortly will be reabsorbed, and we end up with 200-500 milliliters of feces.

Gut as an endocrine organ

The gut (and skin) has a huge role in maintaining microbiota homeostasis, providing multiple benefits to the host including breaking down metabolites, strengthening the immune system, protecting against pathogens, creating a healthy barrier. Some research suggests that the gut microbiome has an immune-modulating potential on distant organ sites (lung, brain, skin) as well. The gut microbiome, as an endocrine organ, produces and/or regulates many hormone-like chemicals which then released into the bloodstream and transported to distal organs (ex. brain). These microbial metabolites includes short chain fatty acids (SCFA), neurotransmitters (serotonin, dopamine), tryptophan (serotonin’s precursor), and choline metabolites. There are still unknown mechanisms of the gut microbiota, but based on recent discoveries, it indirectly controls the hypothalamic-pituitary-adrenal axis (cortisol). Monocolonization by certain bacterial species such as Bifidobacterium infantis, could be a treatment for stress related disorders (GABA neurotransmitter producing strain). Furthermore, the probiotic Lactobacillus rhamnosus PL60 has been shown great results in reducing weight gain and white adipose tissues (without influence of food intake) – this is due to its ability to produce conjugated linoleic acid in our gut. 

As you can see the influence of gut microbiota reaches well beyond its gastrointestinal tract compartment. It is really fascinating!

You are what your microbes can digest

Many of these microorganisms are crucial for metabolic and immune function since they can metabolize complex indigestible polysaccharide into micronutrients such as vitamin K2, vitamin B12, propionate and butyrate. These metabolites are crucial for maintaining epithelial barrier integrity, which in return protects us from harmful substances of the outside world. Diet and hygiene play an important role in the tolerance of immune system. For instance, the Western diet (full of PUFA, refines sugar, processed food) has been shown to contribute to immune-mediated inflammatory diseases – rheumatoid arthritis, psoriasis, dermatitis – which impact the gut health and immune system severely. The western diet is high in fat consumption which creates an imbalance in our gut microbiome, favoring pathogens (Firmicutes) over healthy gut bugs (Bacteroidetes). In our modern urbanized world with an ultra-hygienic lifestyle, we reduce our exposure to microbes which can be the cause of Th2-mediated inflammatory diseases such as asthma and atopic dermatitis. People living on farms or non-urbanized environments are less likely to develop such inflammatory diseases due to augmented microbe stimulation.

When it comes to diet, there are several types of food categories which has been exclusively linked to skin conditions. Legumes from the nightshade family (tomato, eggplant, pepper) have nutritional components such as capsaicin, alpha tomatine, glycoalkaloids, saponins which can worsen intestinal permeability causing inflammatory skin conditions. Similarly, gluten has been associated with skin problems. Individuals who have developed psoriasis or dermatitis, have been also shown to have gluten intolerance, or gluten sensitivity, or celiac disease. Luckily, by removing these food groups for a certain time, the rashes can clear up and heal, and in the meantime a gut healing protocol would be suggested. As I mentioned before, the skin and gut relationship is bidirectional, so the skin could have a beneficial impact on our gut. For instance, skin exposed to sun increases the serum hormone D level which in turn improves the microbe diversity in our gut (Lachnospira, Fusicatenirbacter).

Inflammation

Inflammation and gut dysbiosis goes hand in hand. It is seen in patients with IBD to develop psoriasis (7-11%). Both diseases are immune-modulated disorders. Consequently, the host immune system has a huge role in the interrelationship between gut and skin.  Certain intestinal bacterial species (Lactobacillus, Eubacterium, Bacteroides, Bifidobacterium) use indigested polysaccharides to manufacture fermentation products called SCFAs like butyrate, propionate, and acetate. These metabolites, especially butyrate, are beneficial to enhance epithelial barrier in the gut lumen and to decrease intestinal permeability. The quantity of SCFAs to enter the bloodstream depends on the individual’s fiber intake and microbial fermentation rate. Food components like catechins, polyphenols, lycopene, phytomolecules have amazing anti-inflammatory and anti-aging effects.   All of these factors are determined by what you eat and directly affect the host physiology.

Skin Disorders through the lens of gut microbiome and diet

Alteration of skin microbiome, gut dysbiosis and dietary factors play an important role in several very common skin disorders. Let’s look at a few of them.

Acne Vulgaris

The pathophysiology of Acne Vulgaris is characterized by multiple factors. There is an immunological factor shaped by the innate immune system, adaptive immune system and Th17 pathway. Moreover, there is a hormonal component related to insulin and insulin like growth factor (IGF) concentration. Studies suggest that a deficiency in IGF could protect you from developing acne vulgaris. Diet has been a game changer in acne vulgaris. The therapeutic approach is diverse which implicates its many contributors.

Acne vulgaris affects the sebaceous skin areas (oil producing) including scalp and face. The skin microbiome dysbiosis is mostly associated with a specific strain – Cutibacterium acnes. We have to acknowledge that not all Cutibacterium acne strains are the same in terms of outcome. Some studies suggest that Clade II strains are health-associated, and Clade IA strains are disease-associated. Of course, the more important driver is the diversity of C. acne strains on the skin surface. There are promising alternative treatment options in development which includes the use of probiotics (Lactobacillus, Bifidobacterium).

The first study was made in 1961 establishing a connection between diet and acne vulgaris by the administration of Lactobacillus probiotic supplement. Later in a 2018 study, it became undeniable that patients with acne vulgaris have had a distinct gut microbiome. In these patients, there were a lower abundance of Firmicutes and increased levels of Bacteroides with a less diverse overall microbiome population. Probiotics seems a promising option in treatment, but still needs more study to prove its effectives. As we already established, gut microbiome has a strong influence on our immune systems and immune responses.

As in all types of diseases, diet plays an important factor. High fat and high glycemic diets, like Western diets, have increased the occurrence rate of acne vulgaris. Whereas, in hunter and gatherer cultures, acne vulgaris seems non-existent.

Atopic Dermatitis

Atopic dermatitis is an inflammatory skin diseases affecting large portion of the population (7% adults, 15% children). It is characterized by skin microbial dysbiosis, inflammatory response, and skin barrier dysfunction. It has two components in its development – environment and genetics.  The chronic inflammation in the host is driven by the Th2 pathway, more precisely the cytokines IL-4 and IL-13. These type 2 inflammatory responses play a role not in atopic diseases, but allergic reactions. IL-4 and IL-13 cytokines disrupt the barrier function of the skin by inhibiting the antimicrobial peptide synthesis. This gives a free pass to pathogenic species such as Staphylococcus aureus. Mild cases can be treated with simple natural moisturizers, but in moderate-to-severe cases, the first line treatment by doctors is to target the Th2 inflammatory pathway.

In general, the microbiome of the skin is low in diversity mostly on the lesional skin areas compared to healthy areas. However, there is a relative abundance of Staphylococcus aureus and Staphylococcus epidermis. S. aureus plays a role in the atopic dermatitis severity, causing skin inflammation through the development and penetration of peptidoglycan into the injured skin barrier. The mode of treatment involves the restoration of skin barrier, reduction of pathogenic bacteria and reducing inflammation. Still in clinical trial, but there is great future in bacteriotherapy to treat atopic dermatitis. S. hominis seems to provide protection against S. aureus by producing lantibiotics.

Regarding the gut microbiome implications in AD patients, there is an established correlation between gut dysbiosis and inflammation markers of skin. The gut microbiome of these patients were enriched with Faecalibacterium prausnitzii, Clostridium and Escherichia coli. There can damage the gut epithelium and cause inflammatory state of the host. They also lower the anti-inflammatory butyrate- and propionate-producing species abundance in the gut. Studies suggests that probiotics (Lactobacillus, Bifidobacterium) may prevent the development of atopic dermatitis in infants.

Diet is a key element in the treatment of atopic dermatitis. Omega-6 fatty acids aka PUFA is causing inflammatory reactions in the whole body, including the skin and the gut. PUFA degrades our energy production pathways in the mitochondria, causes oxidative stress, accumulates under the skin as liver spots – it is crucial to avoid any PUFA containing foods which usually the liquid oils such as sunflower oil, flaxseed oil, canola oil etc.

Psoriasis

Psoriasis is an immune-mediated inflammatory disease which affects around 12% of the population worldwide. It is more than just a skin disease, it is rather a systemic disease with several comorbidities present in the patient. It is influence by genetics, environment and lifestyle. Stress seems to be the main triggering or exacerbating factor. Since it is an inflammatory condition, cytokines such as Th-17, TNF and IL-23/IL-17 play a role in mild-severe symptom development.

Psoriasis is mainly characterized by the high abundance of Staphylococcus and Streptococcus species on skin lesion. However, studies show that there is a relatively lower abundance of key microbes such as S. epidemidis and C. acnes which may enable the colonization of S. aureus pathogenic bacteria. Consequently, it has been proven in studies made on mice that S. aureus upregulates Th-17 pro-inflammatory cells which secrete IL-17 cytokine triggering inflammation in skin lesion. This is a natural defense function of our immune system to protect us from pathogenic infections. UVB light therapy has been shown to reduce inflammation and restore the skin microbiome. 

Increased inflammation in psoriasis patient have a great impact on the gut microbiome as well as immune system. Psoriasis patients have greater chance of developing other autoimmune disorders. They are at higher risk of developing intestinal immune disorder, for example celiac disease, IBD and UC. Psoriasis is highly associated with structural aberration in the small intestine. It has been found that the surface of the jejunum (small bowel) is decreased leading to malabsorption of nutrients. Leaky gut or permeability of the intestinal wall has been reported along with lactose intolerance. Intestinal integrity is key in maintaining healthy skin and immune system. Higher levels of fecal calprotectin was found in psoriasis patient which is an indicator of inflammation in the gut – the higher the level was the worse psoriasis were.

Diet and lifestyle factors are crucial in the management of psoriasis. Obesity, smoking, and alcohol are all associated with the exacerbation of skin lesion. Psoriasis can only be controlled by an anti-inflammatory diet while working on the gut. Anti-microbial and immune strengthening herbs are immense help – garlic, oregano oil, clove, turmeric, wormwood, sage. A grated carrot salad with coconut oil and vinegar also supports the digestion and elimination process. While symptoms are present, it is better to remove foods such as diary and all grains. Red light therapy is beneficial for inflammation reduction.

Overall, all skin conditions start in the gut. Gut dysbiosis occurs due inflammation in the body and inadequate lifestyle factors (stress, pollution, chemicals). Supporting your whole body with a nourishing diet and lifestyle is key to heal. Usually, skin conditions are signs of the liver not properly eliminating toxins. Toxins can come from outside (harmful cosmetics, chloride from tap water, mold in the air) and inside (toxins are reabsorbed via leaky gut, pathogens, parasites). All rebalancing process begins by healing the gut which will give a great foundation for healing other dis-eases. Test, don’t guess – GI-MAP stool test can reveal all microbial imbalances and provide you a guidance what you need to focus on. Your healthcare provider can support you with testing, analyzing and supplement suggestions.

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