649 Bidirectional Gut-Skin Axis
that this area of research is still in its infancy and further investigation is required to
understand its mechanisms and potential applications.
Furthermore, it is hypothesized that a signaling pathway of interconnectivity exists between
epithelial organs (the gut and skin), suggesting that host-microbe interactions could disrupt
immune homeostasis across these distant epithelial surfaces.166 This hypothesis aligns with
evidence showing increased incidence of irritable bowel disease (IBD) in patients with
chronic inflammatory skin conditions.3 Additionally, research into Crohn’s disease suggests
that the common commensal fungus Malassezia restricta in the skin microbiome may
influence disease severity, correlating its presence with worsened colitis.167
Research by Bosman et al. (2019) demonstrated that exposure of the skin to narrow-band
UVB (NB-UVB) modulates the gut microbiome, further supporting the existence of a skin-
gut axis.168 NB-UVB exposure increased serum vitamin D levels, correlating with changes
in the relative abundance of specific gut bacteria, particularly within the Lachnospiraceae
family such as Lachnospira and Fusicatenibacter.168 It is hypothesized that UVB-induced
immune modulation initiates changes that extend from the local skin environment to the
gut microbiome.169 Despite the limitations of 16S rRNA sequencing, functional analyses
through metabolomics or metagenomics are needed to fully understand the implications of
selective gut microbiome modifications observed in this study.168 Nevertheless, regulatory
effects on the gut microbiome observed in this context may offer potential health benefits.
Lastly, Kuo et al. (2022) investigated the contribution of the skin–gut axis to immune-related
adverse events (irAEs) in cancer patients undergoing immunotherapy.170 Both the skin and
GI tract are organs that commonly exhibit symptoms of irAEs due to heightened immune
responses in these patients. The researchers identified a significant correlation between
these events, noting that skin-related irAEs often preceded GI irAEs in their cohort. This
suggests a potential predictive relationship between skin and gut manifestations of irAEs
during cancer immunotherapy, highlighting a potential communication pathway from
cutaneous skin inflammation to gut responses.170 As skin inflammation leads to hyaluronic
acid breakdown and the release of fragments that can induce differentiation of intestinal
fibroblasts into preadipocytes, researchers postulate that this signaling may prepare the
gut to respond to the source of skin inflammation, potentially explaining the sequential
occurrence of GI irAEs following skin irAEs.166 However, further research is warranted, as
multiple mechanisms, including the skin-gut axis, contribute to GI irAEs.170
FUTURE PROSPECTS: THE SKIN-GUT AXIS AND POTENTIAL THERAPEUTIC
AND COSMETIC APPLICATIONS
Given the evidence supporting the gut-skin axis and the broader skin-gut axis, there are
promising opportunities for novel cosmetic and therapeutic interventions. The bidirectional
nature of this axis highlights the necessity for further research to utilize it for beneficial
health outcomes. Although current research has investigated the impact of skin injuries
on gut health, exploring non-invasive strategies to utilize this relationship could lead to
innovative treatments and advancements in human health.
Both the gut and skin microbiomes are critical regulators of the immune system and are
essential for maintaining homeostasis. These organs share several characteristics: the inner
surface of the gut and the outer surface of the skin are both covered by epithelial cells that
interfere directly with the exogenous environment.171 Additionally, both organs are highly

650 JOURNAL OF COSMETIC SCIENCE
innervated and vascularized, playing vital roles in immune response and neuroendocrine
function.30 Thus, the similarities and the interconnectedness of their respective microbiomes
highlight the importance of maintaining balance in both for overall systemic health.30
Disruptions in one organ can lead to dysbiosis in the other, as emerging research illustrates
the immunomodulating potential of microbiomes on distant organs.3
The application of therapeutic and nutricosmetic interventions based on the gut-skin axis
suggests that similar approaches might be possible for the skin-gut axis in the future, raising
intriguing possibilities for researchers to design and create novel cosmetic and therapeutic
products. For example, the aforementioned research by Dokoshi et al. (2024), that shows
how cutaneous inflammation can alter the gut microbiome, may guide the development of
cosmetic products that enhance dermal stability and prevent disturbances in both the skin
and gut microbiome.6 Formulating products to reduce skin inflammation could, in turn,
help avert gut microbiome dysbiosis, potentially through topical synbiotics or LBPs.
Transdermal therapeutics exemplify how skin-targeted treatments can achieve systemic
effects.172 Although the concept of transdermal drug delivery dates back to 3000 BC with
use in ancient Egyptian and Babylonian medicine, it only became widespread in the latter
part of the 20th century. This shift occurred with advancements in delivery technologies
that allowed for the precise and consistent administration of medication through the
skin.173 Notable and relevant examples include the daily application of patented vitamin
D3 patches, which effectively increase serum 25-hydroxyvitamin D (25(OH)D) levels, and
studies involving biomimetic nanovesicles (tiny vesicle-like structures designed to mimic
biological membranes) loaded with folic acid and iron incorporated into polyacrylate-based
transdermal patches.172,174 These nanovesicles demonstrated the ability to fluidize skin
lipids and penetrate deeper layers, thereby enhancing nutrient absorption.174
Furthermore, the emerging field of neurocosmetics, which harnesses the skin-brain axis to
influence interactions between the skin and the nervous system through skincare products,
offers a potential framework for future applications involving the skin-gut axis.175 This field
encompasses a range of functional ingredients and commercial products that are specifically
designed to be applied to the skin and subsequently operate at a neurological level. These
products affect the cutaneous nervous system and modulate the skin’s neuromediators
through various mechanisms of action, and the skin-gut axis may be affected similarly.175
While extensive research is essential to fully elucidate the bidirectional nature of the gut-
skin/skin-gut axis, the expanding body of literature on this communication pathway is
both exciting and promising.6,166,168,170 This ongoing investigation into the gut-skin axis
has highlighted its significant role in various skin conditions and overall skin health,
underscoring one aspect of this complex relationship. Moreover, understanding the reverse
skin-gut axis opens new avenues for developing innovative treatments and strategies. By
leveraging the accessibility of the skin—the body’s largest organ—and its interconnectedness
with other organs, researchers can explore both therapeutic and cosmetic approaches to
achieve systemic benefits.
REFERENCES
(1) Aggarwal N, Kitano S, Puah GRY, Kittelmann S, Hwang IY, Chang MW. Microbiome and human
health: current understanding, engineering, and enabling technologies. Chem Rev. 2023 123(1):31–72.
doi:10.1021/acs.chemrev.2c00431