The gut microbiome in skin disease

What is the human microbiome?

Our bodies share a symbiotic relationship with trillions of microbes including bacteria, fungi, mites, and viruses. Together, they make up the microbiome, which resides in particular areas of the body such as the skin and gut [1].

These microbes do not cause harm under normal conditions but directly influence the body’s normal function and disease processes [2–4].

Human gastrointestinal tract

Representation of the intestinal lining with and without microbiota

What is the gut microbiome?

The mucosal lining of the gastrointestinal tract is home to millions of organisms [2]. Its composition varies with Bacteroidetes, Firmicutes, Actinobacteria, and Proteobacteria dominating the gut microbiome of adults [2,5].

The relationship between the gut microbiome and immunity is currently a major topic of research.

Bacteriodes

Actinomyces israelii

Escherichia coli

What factors affect the gut microbiome?

The gut microbiome changes over the first three years of life before forming a relatively stable composition [2]. It also varies greatly from person to person and is dynamic within an individual over time [5]. Factors that influence the gut microbiome include:

• Genetics
• The mode of delivery at birth
• Breastfeeding
• Age
• Diet
• Environmental microbes
• The use of certain medications, particularly antibiotics and proton pump inhibitors [5,6].

What is the function of the gut microbiome? 

The gut microbiome has several important roles in health, particularly in metabolism and the immune system. These include roles in:

• Protection against inflammatory disorders [2]
• Contributing to the development of the immune system [2,3]
• Protection against harmful pathogens [2]
• Facilitating the immune system to recognise harmful versus non-harmful molecules (immune tolerance) [2,3,7]
• Breaking down complex polysaccharides in food and the production of short-chain fatty acids [2]
• Production of vitamin K, required for blood clotting [5,7].

What are short-chain fatty acids?

One important function of microbes in the gut flora is the production of short-chain fatty acids via the break-down of complex carbohydrates in food [2,3]. Examples of short-chain fatty acids are propionate, acetate, and butyrate.

Short-chain fatty acids are thought to:

• Help maintain the balance in the gut between its inflammatory and regulatory functions [2]
• Have a role in determining the microbial composition of the skin, resulting in protective effects against inflammation [3]
• Have an antimicrobial effect on methicillin-resistant Staphylococcus aureus [3]
• Contribute to the prevention of inflammatory disorders and allergy [3].

What is the connection between the gut microbiome and the immune system?

Alterations in the gut composition, the diversity of the microbiome, and abnormal immune reactions to the microbes may result in changes to the immune and regulatory functions of the gut [3,8]. These changes may ultimately lead to local or systemic immune dysfunction affecting the skin [9,10].

Disruption in the gut microbiome has been associated with allergic, inflammatory, autoimmune, metabolic, neuropsychiatric, and neoplastic diseases [2,3,10,11].

The gut microbiome and the skin

The gut and the skin are suspected to have a bidirectional relationship involving a combination of neurological and immunological responses to changes in the microbiota [2,8]. Mechanisms by which the gut flora is thought to influence the skin include:

• Anti-inflammatory effects
  • Certain microbes promote white blood cells which contribute to anti-inflammatory responses [8]
  • Short-chain fatty acids inhibit inflammation and regulate immune cells [3]
• Increased intestinal permeability
  • Changes in gut flora may increase the permeability of the intestine with subsequent leakage of gut microbiota into the bloodstream and skin resulting in systemic or cutaneous inflammation [2,3]
• Neurotransmitters
  • Gut organisms alter levels of neurotransmitters which may influence the skin [2].

The gut microbiome and atopic dermatitis

Some studies have observed that gut dysbiosis (microbial imbalance) precedes the onset of atopic dermatitis [3,11,12]. Although the relationship is not clear, there are distinct differences in the gut microbiome between people with and without atopic dermatitis.

Infants who go on to develop atopic dermatitis have been reported to have:

• Lower colonic microbial diversity [12]
• Altered gut levels of certain gut bacteria (Staphylococcus aureus, Bacteriodetes and Clostridia [2,11])
• Lower levels of Bifidobacterium levels, which are inversely correlated with severity [7]
• Lower levels of Bacteroides and certain mucin-producing bacteria (Akkermansia muciniphila, Ruminococcus gnavus, and Lachnospiraceae) [7,11].

The gut microbiome and acne

Observed changes in microbial composition between individuals with and without acne may be due to:

• Interactions with the mammalian target of rapamycin (mTOR) pathway and its effects on the intestinal barrier and metabolic function [3]
• Dysbiosis stimulated by psychological stress and diet resulting in systemic inflammation [3].

Other

Small studies have reported possible associations of alterations in the gut microbiome with rosacea, psoriasis, and wound healing [3,5,9].

What are probiotics, prebiotics, and synbiotics?

Probiotics are defined by the World Health Organisation (WHO) as “live microorganisms which when administered in adequate amounts, confer a health benefit on the host” [5,10]. The most commonly used bacteria in probiotics are Lactobacilli and Bifidobacteria [2,5].

Prebiotics are non-digestible fibres that stimulate certain beneficial bacteria in the gut. The most common of these are non-digestible oligosaccharides [2].

Synbiotics are a combination of probiotics and prebiotics [2].

What is the role of probiotics, prebiotics, and synbiotics in skin disease?

The main role of probiotics and prebiotics is to restore and encourage the production of beneficial microorganisms in the gut [2]. Research is focusing on their therapeutic potential and results to date have been conflicting [9].

The role of probiotic supplements in the prevention of atopic dermatitis is being investigated in pregnancy and infancy to determine if they can improve or help prevent skin disease [2,11]. Probiotics have not been shown to treat established dermatitis [5,12].

It has been reported that probiotics may lead to an improvement in acne by reducing inflammation and decreasing ceramide production [12].