Atopic dermatitis (AD) is a highly prevalent, chronic inflammatory condition that significantly impacts quality of life.¹ Individuals with AD suffer from dry, itchy, irritable skin. The pathophysiology of AD is multifaceted and includes genetic predisposition, immune dysregulation, and skin barrier disruption.² The gut microbiome has been correlated with and is implicated in the pathogenesis of AD.³

AD (eczema) involves complex interactions between genetics, a compromised skin barrier, and microbial imbalances (dysbiosis) in both the skin and gut.⁴ The advent of genetic sequencing has revealed that specific bacterial shifts (eg, less Bifidobacterium, more Staphylococcus aureus)⁵ and reduced anti-inflammatory short-chain fatty acids (SCFAs) in the gut are correlated with an increased risk of AD prevalence.⁶ These observations have led to the hypothesis of the existence of a gut-skin axis, or a strong connection between AD and impaired gut microbiome function. Shifts from a traditional diet to processed food, allergens, pollution, medications, and many other factors lead to a diminished diversity in the gut microbiome and dramatic reductions in SCFA’s which are critical for gut health and for supporting the gut-mediated immune system.⁷ Lack of SCFA’s often leads to a compromised epithelial layer in the gut leading to “leaky gut” and “translocation.”⁸ Research has demonstrated a relationship between increased intestinal permeability and AD and its severity.^9,10

Standard treatment of AD includes topical corticosteroids (TCs), and regular emollient use to inhibit water loss and restore skin barrier.¹¹ While TCs are efficacious in treating AD, prolonged TC use causes loss of dermal connective tissue, specifically loss of stratum granulosum (SG), and SC thinning, leading to erythema, telangiectasia, or purpura.¹²

Furthermore, there is an increasing interest in integrative, non-pharmacological alternatives to TC’s; recent discoveries on how the skin and gut microbiota modulate AD pathogenesis point to the potential to manipulate commensal gut bacteria to prevent and manage AD.¹³ Manipulation of the gut microbiome can be achieved through the use of both pre- and pro-biotic supplements. Prebiotics serve as substrates that are metabolized by members of the gut microbiome and can result in health benefits when ingested through dietary sources and supplements. For example, they can be used to stimulate the growth of commensal and keystone species in the gut that are necessary to produce SCFA’s and support cross-feeding in the microbiome. Probiotics, which are microorganisms themselves, can be used as supplements to support the populations of these critical species, and through their decay and disintegration can stimulate specific activities in the gut immune system thereby reducing inflammation.^14,15 It is also realized that there are both internal factors (such as gut dysbiosis and intestinal permeability), and external factors (such skin inflammation and dysfunction of the skin barrier) that may contribute to the development or aggravation of eczema. Therefore, our study has also addressed the external factors with an appropriate plant-biotech topical moisturizer and high-glycerin soap. These topicals alone have been demonstrated to reduce AD severity score and improve skin barrier integrity and function in adults with mild to moderate AD.¹⁶

This open label clinical pilot study investigates the effect of an integrative approach with the use of an oral prebiotic and probiotic food supplement in conjunction with a plant-biotech moisturizer and an unscented soap on AD severity, pruritus, and skin biophysical measures in those with moderate AD.

The combination of prebiotic and probiotic oral supplements, a botanical moisturizer, and an unscented soap, were associated with significant improvements in AD severity, pruritus, TEWL, skin hydration, and desquamation after 8 weeks. Skin biophysical improvements were observed as early as D28 with continued improvement to D56.

This study demonstrated > 90% reduction in pruritus NRS, and 88% subjects experienced minimal pruritus at D56. These improvements may be attributed to the anti-inflammatory effects of fucoidans from Padina pavonica,¹⁸ the allantoin from the Symphytum officinale,¹⁹ as well as the anti-inflammatory and anti-pruritic effects of avenanthramides in colloidal oatmeal in the moisturizer.²⁰

Since pruritus has also been positively correlated with TEWL and inversely correlated with skin hydration,²¹ the reduction in itch may also be related to the effects of the botanical moisturizer and soap in the regimen that decreases TEWL and increases hydration by strengthening the skin barrier.

For example, myconoside from Haberlea rhodopensis, a botanical in the moisturizer, helps stimulate extracellular matrix synthesis and improve skin barrier cohesion, while laminarins, fucoidans, and alginic acids from Padina pavonica can hydrate the skin and reduce inflammation.^22,23 The moisturizer also contains hyaluronic acid, omega6 linoleic acid from sunflower oil, and ceramide NP to strengthen atopic skin, where ceramides and omega6 fatty acids are markedly reduced and associated with increased trans-epidermal water loss.²⁴ Skin hydration is further supported by the soap’s high glycerin content, which acts as a humectant and may help limit barrier damage.^25–28

The 93% reduction in total SCORAD may in part be attributed to these topical ingredients in combination with daily prebiotic and probiotic supplementation targeted at supporting the gut microbiome’s keystone species. Research shows that the “inside-out” mechanism (eg, the gut microbiome) has been implicated in the genesis and/or amplification of AD.²⁹ The gut microbiome provides the ability to digest food and generates SCFA’s which are necessary for human survival. Some of the SCFA’s (eg, butyrate) modulate the gut immune function,³⁰ are the primary source of energy for the colonic epithelial cells, and aid or enable many other critical functions within the body. It has also been observed that the Western diet, exposure to pollutants, allergens, antibiotics and other medicines all lead to a reduction in gut diversity and often to a reduction in function of the gut microbiome and/or dysbiosis.

Prebiotics and probiotics offer one potential way to ameliorate the aforementioned issues. Prebiotics support the growth of commensal and keystone species by supplying many of the nutrients (resistant starches, oligosaccharides, polyphenols) of which patients are bereft. Probiotics, which have been studied for far longer, can substitute functionally for some of the missing species/strains (eg, Lactobacillus, Bacteroidetes) and have the potential to interact with the gut immune system to reduce many symptoms as well as help reduce translocation.³¹

Recent research indicates that 25% of US infants lack a detectable amount of the keystone species Bifidobacterium; and in particular the strains that predominate in infants (B. longum, B. breve, B. infantis).³² The same paper notes a correlation between the dearth of this keystone species and AD. Given this correlation our probiotic supplement contains 4 strains of Bifidobacterium in addition to 8 strains of anti-inflammatory Lactobacillus. We suspect that a percentage of the improvement noted in the study may be attributed to supplementation with these strains. Further, the prebiotic, rich in resistant potato starch which fosters the growth of Bifidobacterium,³³ and has been found to reduce markers of intestinal permeability,³⁴ which has been correlated to AD.^9,10

This study has several limitations. It was open label, which increases the potential for bias; however, the biophysical skin measurements were quantitative and internally controlled by comparison to non-lesional skin on the same subject, making them less vulnerable to this limitation and supporting the observed improvements in AD severity scores. The sample size seems to be relatively small, but this is a study where the patient is their own control, and the values are compared between the beginning of the treatment and throughout the treatment. This provides statistical power at least equivalent to comparing two groups of 60 subjects each. Further, the study population was predominantly female, so the findings may not be fully generalizable across genders. In addition, all participants in the study had a Fitzpatrick skin type II, and pregnant or nursing women, or women planning or get pregnant during the study were excluded from the trial. Future research should include larger, more diverse populations and use a double-blind, placebo-controlled design. A head-to-head study comparing this regimen with topical conventional treatment regimens would help elucidate efficacy and safety of alternative solutions for patients seeking alternatives.

This study evaluated a combination regimen designed to address multiple factors in AD, so it does not isolate the effects of individual ingredients; many of the actives are already supported by prior research and this work extends those findings in a real-world regimen. Future studies that explore the use of each individual product as monotherapy on a similar participant population would provide further insight into individual product effects on moderate AD and provide more data that can be used to compare the efficacy product monotherapy to the combination regimen assessed in this study. In addition, the study was limited to participants with moderate AD, and no conclusions can be drawn about its impact on severe disease.

In conclusion, an eight-week integrative regimen including prebiotic and probiotic supplementation with a topical botanical moisturizer and high-glycerin soap was associated with efficacy in reducing AD severity, pruritus, and improving skin biophysical properties in participants with moderate AD. Given the open-label, single-arm pilot study design of this trial, the findings are exploratory and further research will be needed to better understand the efficacy of the study interventions and their role in the multifactorial pathophysiology of AD.

Funding for this study was provided by Codex Labs.