648 JOURNAL OF COSMETIC SCIENCE
Figure 2. The impact of skin injury on the gut and overall system health by means of the skin-gut axis. Skin
injuries affect the gut microbiome and overall systemic health through the skin-gut axis. Wounding triggers
hyaluronan degradation, which activates immune responses and inflammation through IL-6 secretion.
This process upregulates host defense genes Reg3 and Muc2. The resulting changes in the gut microbiome
include an increase in pathogenic bacteria and enhanced colon epithelial penetration, potentially leading to
cascading effects on systemic health and suggesting a mechanism by which skin injuries may impact broader
physiological functions.

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