Cutibacterium acnes-derived short-chain fatty acids drive lipogenesis and induce holocrine secretion in human sebocytes
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (PREreview)
Abstract
Sebum lipids are one of the key ecological determinants of skin microbiome composition, where sebaceous sites are enriched with sebum utilising microbes such as Cutibacterium acnes. While sebaceous gland (SG) activation and sebogenesis are classically viewed as host-regulated processes, the association of C. acnes expansion with sebum production in the skin suggests a possible bidirectional host-microbe regulation. Using bacterial supernatants, we combined image-based lipid quantification, GC-FID metabolite profiling, lipid secretion quantification, and transcriptomic analysis to determine the metabolic drivers of the interaction between C. acnes and sebocytes. We found that C. acnes secretome significantly increased lipid droplet accumulation in sebocytes and propionate as the primary driver of this lipogenic response. Mechanistically, propionate reprogrammed the central carbon metabolism, redirecting carbon flux toward energy production and generation of precursors for lipid biosynthesis. Propionate also promoted lipid assembly pathways and modulated the composition of the secreted lipids from the treated sebocytes. We further show that propionate promotes expression of late sebocyte differentiation markers associated with holocrine secretion. Together, these findings redefine the relationship between microbiome and sebaceous glands, and identify C. canes as an active regulator promoting both sebogenesis and holocrine secretion for the release of lipids in the pilosebaceous unit.
Article activity feed
-
This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/22958790.
The experimental framework mapping how Cutibacterium acnes-derived short-chain fatty acids (SCFAs) modulate intracellular lipogenesis and trigger downstream holocrine secretory dynamics in human sebocytes offers critical metabolic insights. Evaluating these bacterial-host interaction channels expands our understanding of skin microbiome-mediated lipid homeostasis without relying on generalized phenotypic observations.
However, from a structural biochemistry perspective, the study design requires tighter calibration parameters regarding the exact concentration thresholds of the bacterial metabolites used to simulate the response. The authors must fully document whether the observed …
This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/22958790.
The experimental framework mapping how Cutibacterium acnes-derived short-chain fatty acids (SCFAs) modulate intracellular lipogenesis and trigger downstream holocrine secretory dynamics in human sebocytes offers critical metabolic insights. Evaluating these bacterial-host interaction channels expands our understanding of skin microbiome-mediated lipid homeostasis without relying on generalized phenotypic observations.
However, from a structural biochemistry perspective, the study design requires tighter calibration parameters regarding the exact concentration thresholds of the bacterial metabolites used to simulate the response. The authors must fully document whether the observed lipogenic acceleration is a specific receptor-mediated signaling event or a broader cellular stress-response pathway triggered by altered microenvironmental pH. Reporting the precise intra-assay coefficients of variation for the lipid accumulation metrics is necessary to resolve these mechanistic ambiguities.
Additionally, investigating how these specific fatty acid fractions alter local epithelial barrier integrity during prolonged exposure would provide a stronger validation benchmark. This technical adjustment increases the study's predictive utility for independent investigators developing targeted structural biology interventions to disrupt dysregulated sebaceous networks.
Competing interests
The author declares that they have no competing interests.
Use of Artificial Intelligence (AI)
The author declares that they did not use generative AI to come up with new ideas for their review.
-
This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/22958917.
The experimental framework mapping how Cutibacterium acnes-derived short-chain fatty acids (SCFAs) modulate intracellular lipogenesis and trigger downstream holocrine secretory dynamics in human sebocytes offers critical metabolic insights. Evaluating these bacterial-host interaction channels expands our understanding of skin microbiome-mediated lipid homeostasis without relying on generalized phenotypic observations.
However, from a structural biochemistry perspective, the study design requires tighter calibration parameters regarding the exact concentration thresholds of the bacterial metabolites used to simulate the response. The authors must fully document whether the observed …
This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/22958917.
The experimental framework mapping how Cutibacterium acnes-derived short-chain fatty acids (SCFAs) modulate intracellular lipogenesis and trigger downstream holocrine secretory dynamics in human sebocytes offers critical metabolic insights. Evaluating these bacterial-host interaction channels expands our understanding of skin microbiome-mediated lipid homeostasis without relying on generalized phenotypic observations.
However, from a structural biochemistry perspective, the study design requires tighter calibration parameters regarding the exact concentration thresholds of the bacterial metabolites used to simulate the response. The authors must fully document whether the observed lipogenic acceleration is a specific receptor-mediated signaling event or a broader cellular stress-response pathway triggered by altered microenvironmental pH. Reporting the precise intra-assay coefficients of variation for the lipid accumulation metrics is necessary to resolve these mechanistic ambiguities.
Additionally, investigating how these specific fatty acid fractions alter local epithelial barrier integrity during prolonged exposure would provide a stronger validation benchmark. This technical adjustment increases the study's predictive utility for independent investigators developing targeted structural biology interventions to disrupt dysregulated sebaceous networks.
Competing interests
The author declares that they have no competing interests.
Use of Artificial Intelligence (AI)
The author declares that they did not use generative AI to come up with new ideas for their review.
-
This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/22959092.
The experimental framework mapping how Cutibacterium acnes-derived short-chain fatty acids (SCFAs) modulate intracellular lipogenesis and trigger downstream holocrine secretory dynamics in human sebocytes offers critical metabolic insights. Evaluating these bacterial-host interaction channels expands our understanding of skin microbiome-mediated lipid homeostasis without relying on generalized phenotypic observations.
However, from a structural biochemistry perspective, the study design requires tighter calibration parameters regarding the exact concentration thresholds of the bacterial metabolites used to simulate the response. The authors must fully document whether the observed …
This Zenodo record is a permanently preserved version of a PREreview. You can view the complete PREreview at https://prereview.org/reviews/22959092.
The experimental framework mapping how Cutibacterium acnes-derived short-chain fatty acids (SCFAs) modulate intracellular lipogenesis and trigger downstream holocrine secretory dynamics in human sebocytes offers critical metabolic insights. Evaluating these bacterial-host interaction channels expands our understanding of skin microbiome-mediated lipid homeostasis without relying on generalized phenotypic observations.
However, from a structural biochemistry perspective, the study design requires tighter calibration parameters regarding the exact concentration thresholds of the bacterial metabolites used to simulate the response. The authors must fully document whether the observed lipogenic acceleration is a specific receptor-mediated signaling event or a broader cellular stress-response pathway triggered by altered microenvironmental pH. Reporting the precise intra-assay coefficients of variation for the lipid accumulation metrics is necessary to resolve these mechanistic ambiguities.
Additionally, investigating how these specific fatty acid fractions alter local epithelial barrier integrity during prolonged exposure would provide a stronger validation benchmark. This technical adjustment increases the study's predictive utility for independent investigators developing targeted structural biology interventions to disrupt dysregulated sebaceous networks.
Competing interests
The author declares that they have no competing interests.
Use of Artificial Intelligence (AI)
The author declares that they did not use generative AI to come up with new ideas for their review.
-
