Cutibacterium acnes-derived short-chain fatty acids drive lipogenesis and induce holocrine secretion in human sebocytes
- 1LOreal Research & Innovation, 1 Raffles Quay, North Tower, Singapore 048583, Singapore
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.
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BibTeX
@misc{low2026cutibacterium,
title = {{Cutibacterium acnes-derived short-chain fatty acids drive lipogenesis and induce holocrine secretion in human sebocytes}},
author = {A. D. Low and O. Kulkarni and F. Brillet and E. Kaliyamoorthy and A. Tay and S. Rice and V. Rasheedkhan Regina and T. Chopra},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.23.753677},
url = {https://www.biorxiv.org/content/10.64898/2026.09.23.753677v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - Cutibacterium acnes-derived short-chain fatty acids drive lipogenesis and induce holocrine secretion in human sebocytes
AU - A. D. Low
AU - O. Kulkarni
AU - F. Brillet
AU - E. Kaliyamoorthy
AU - A. Tay
AU - S. Rice
AU - V. Rasheedkhan Regina
AU - T. Chopra
PY - 2026
DA - 2026/09/23
PB - bioRxiv
DO - 10.64898/2026.09.23.753677
UR - https://www.biorxiv.org/content/10.64898/2026.09.23.753677v1
AB - 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.
ER -