SCFAs and Skin Health

‘It’s easier to fool people than to convince them they have been fooled’ attributed to Mark Twain

The relationship between the gut and skin health has been one of contention for several years. Primarily, the mechanism requires there to be an agreement that the outcome of digestion impacts skin quality. This may seem an obvious connection, but for many people, this is either not understood or denied, often supported by well-meaning clinicians who are also unaware of the important connection.

A paper in the June 2022 edition of Mucosal Immunity adds to the growing understanding of how and why food selection, microbiota composition, and related production of short-chain fatty acids (SCFAS) are key players in skin health[1].

Gut-Skin Axis (GSA)

The GSA describes the relationship where the gut can influence skin health owing to its immunological and metabolic properties[2]. Although it is difficult to strictly attribute a cause-and-effect relationship between the gut microbiome and dermatologic conditions, multiple studies support a connection between them with several cutaneous diseases being associated with GI disorders and vice versa. For example, 10-25% of patients with GI diseases, such as ulcerative colitis, Crohn’s, and coeliac disease also present with associated cutaneous findings, particularly psoriasis and cutaneous ulcers.

About 60 tons of food is estimated to pass through the gut in a lifetime, all of which have a big impact on human health[3]. Food selection is understood to have a direct impact on the compositional mix of resident microbiota in the gut, with the opportunity for mediation of local and systemic immune responses. Their related microbiome is a key regulator for the immune system, as it aims to maintain homeostasis by communicating with tissues and organs in a bidirectional manner.

The Skin Microbiome

The skin microbiome has also gained significant attention in recent years in dermatology, skin disorders, and its connection and influence on the immune system[4]. Many skin conditions are associated with an imbalance in the skin microbiome and the gut microbiome and related barriers. Intestinal barrier integrity plays a crucial role in protecting microbiota from entering the systemic circulation and in avoiding inflammation in the gut. Diet can have a vital role in the maintenance of particular skin pathologies when those food ingredients impair the intestinal barrier, which leads to gut bacteria entering the bloodstream.

Gut Skin Vit D Axis

However, the GSA not only is governed by diet but also acts bidirectionally. Skin exposure to ultraviolet B (UVB) and therefore indirectly to serum vitamin D levels increase the α and β diversity of the gut microbiome[5]. Researchers concluded that UVB light can rapidly modulate the gut microbiome without any dietary changes. Therefore, it cannot be excluded that sun exposure contributes to the seasonal variation in microbiome compositions. While the seasonal variation of the microbiome might not have overt effects on healthy individuals, it could be of greater importance for people with immune dysfunction.

Probiotics

Under normal conditions, the population of A. muciniphila composes approximately 3%-5% of the intestinal species in an adult colon and accounts for more than 1% of the total microbiota in the stool, suggesting that this bacterium is one of the most abundant in the microbial community. Recent studies showed that A. muciniphila could associate with intestinal cells to maintain cellular barrier function, while a dietary intervention study demonstrated that A. muciniphila may act as an indicator of health status. Low levels of this probiotic in people with psoriasis suggest there may be an important role to play with dietary and probiotic supplementation[6].

Several studies have been conducted for atopic dermatitis (AD) prevention in children with probiotics, administering them both to their mother during pregnancy and to the child in the first months of life. The results are encouraging, even if the results cannot be compared easily given the diversity in the type, dose, and timing of probiotic administration as well as the period of follow-up post-treatment [7]. Both Lactobacilli and Bifidobacteria strains have the potential for improved inflammation and barrier management and are safe and easy to administer at any age, by mixing with drinks or by taking in various forms[8].

Microbiome modulation as a therapy

The single therapeutic application of a single or combination of strains may be able to impact dermatological disturbances when very young, but as we age there needs to be a greater emphasis on the holistic nature of therapeutic changes[9]. However, using the gastrointestinal microbiome as a therapeutic approach has increasingly positive implications. Rather than using anti-biotics, which have long been the strategy for many chronic skin complaints with all the downstream complications[10]. The effects of antibiotics on the host through the gut microbiome are immense and can affect various functions including immune regulation, metabolic activities, and thus overall health. Probiotics and prebiotics can represent a strategic approach with systemic benefits[11].

In this study, kefir intake for eight weeks caused an improvement in the skin condition of healthy subjects, quantitatively demonstrated by a significant decrease in transepidermal water loss and an increase in hydration on the forearm and forehead, compared to the control. Similar results were found in other in vivo studies evaluating the effect of ingested specific probiotic strains (Lactobacillus and Bifidobacterium species) in human adults with healthy skin. Furthermore, their data also showed a significant decrease in the scoring atopic dermatitis (SCORAD) index in the kefir ingestion group compared to controls, with the level of AD severity changing from severe to mild, which reflects a notable clinical improvement.

Conclusion

Exactly how the gut microbiome is related to skin inflammation and influences the pathophysiology mechanism of skin disorders is still under investigation. Many studies have shown a two-way relationship between gut and skin associated with GI health and skin homeostasis and allostasis[12]. Most of the articles agree that Bifidobacterium plays an essential role as anti-inflammation bacteria, and Proteobacteria and Enterobacteria impact inflammation in inflammatory skin disorders. Akkermansia may also be an important mediator – what is recognised is that SCFA’s generated by the microbial fermentation of dietary fibre are significant mediators.

To keep healthy and to resolve unhealthy skin the use of butyrate and the generation of SCFAs represents a safe and useful therapeutic option[13]. Among SCFAs, butyrate suppresses immune responses by inhibiting cytokines and inflammatory cell production, and through the HDAC inhibition promotes Tregs proliferation, the main cells involved in many physiologic functions of the skin, such as hair follicle regulation, stem cell differentiation, and wound healing[14].

Over the last two decades, considerable progress has been achieved. From initial clinical observations to more mechanistic approaches, the field of gut microbiota and health including skin health is evolving to irrefutable causal links[15]. However, there are still numerous studies that claim causality when in fact only correlations are being demonstrated. Moving from correlation to causality remains an important and required step to better design putative interventions based on the modulation of the gut microbiota or by using specific active compounds.

As Mark Twain is alleged to have said, untangling people from beliefs that there is no relationship between diet and skin health may take some time, indeed the studies to date have strong indications of the inter-relationship across skin conditions and ages. But as probiotics can have differing outcomes depending on many social and environmental factors it comes down to the importance of individualised therapy.

References

[1] Trompette, A., Pernot, J., Perdijk, O. et al. Gut-derived short-chain fatty acids modulate skin barrier integrity by promoting keratinocyte metabolism and differentiation. Mucosal Immunol (2022).

[2] Sinha S, Lin G, Ferenczi K. The skin microbiome and the gut-skin axis. Clin Dermatol. 2021 Sep-Oct;39(5):829-839.

[3] Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017 May 16;474(11):1823-1836. doi: 10.1042/BCJ20160510. PMID: 28512250; PMCID: PMC5433529.

[4] De Pessemier B, Grine L, Debaere M, Maes A, Paetzold B, Callewaert C. Gut-Skin Axis: Current Knowledge of the Interrelationship between Microbial Dysbiosis and Skin Conditions. Microorganisms. 2021;9(2):353. Published 2021 Feb 11.

[5] Bosman ES, Albert AY, Lui H, Dutz JP, Vallance BA. Skin Exposure to Narrow Band Ultraviolet (UVB) Light Modulates the Human Intestinal Microbiome. Front Microbiol. 2019 Oct 24;10:2410.

[6] Tan L, Zhao S, Zhu W, Wu L, Li J, Shen M, Lei L, Chen X, Peng C. The Akkermansia muciniphila is a gut microbiota signature in psoriasis. Exp Dermatol. 2018 Feb;27(2):144-149..

[7] Anania C, Brindisi G, Martinelli I, et al. Probiotics Function in Preventing Atopic Dermatitis in Children. Int J Mol Sci. 2022;23(10):5409. Published 2022 May 12.

[8] Yoon W, Park SH, Lee JS, Byeon JH, Kim SH, Lim J, Yoo Y. Probiotic mixture reduces gut inflammation and microbial dysbiosis in children with atopic dermatitis. Australas J Dermatol. 2021 Aug;62(3):e386-e392.

[9] Alves E, Gregório J, Baby AR, Rijo P, Rodrigues LM, Rosado C. Homemade Kefir Consumption Improves Skin Condition-A Study Conducted in Healthy and Atopic Volunteers. Foods. 2021 Nov 13;10(11):2794..

[10] Patangia DV, Anthony Ryan C, Dempsey E, Paul Ross R, Stanton C. Impact of antibiotics on the human microbiome and consequences for host health. Microbiologyopen. 2022;11(1):e1260.

[11] Notay M, Foolad N, Vaughn AR, Sivamani RK. Probiotics, Prebiotics, and Synbiotics for the Treatment and Prevention of Adult Dermatological Diseases. Am J Clin Dermatol. 2017 Dec;18(6):721-732.

[12] Widhiati S, Purnomosari D, Wibawa T, Soebono H. The role of gut microbiome in inflammatory skin disorders: A systematic review. Dermatol Reports. 2021;14(1):9188. Published 2021 Dec 28.

[13] Coppola S, Avagliano C, Sacchi A, et al. Potential Clinical Applications of the Postbiotic Butyrate in Human Skin Diseases. Molecules. 2022;27(6):1849. Published 2022 Mar 12.

[14] Meijer K., de Vos P., Priebe M.G. Butyrate and other short-chain fatty acids as modulators of immunity: What relevance for health? Curr. Opin. Clin. Nutr. Metab. Care. 2010;13:715–721.

[15] de Vos WM, Tilg H, Van Hul M, Cani PD. Gut microbiome and health: mechanistic insights. Gut. 2022;71(5):1020-1032.