PREreviews of Cutibacterium acnes-derived short-chain fatty acids drive lipogenesis and induce holocrine secretion in human sebocytes | PREreview

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Cutibacterium acnes-derived short-chain fatty acids drive lipogenesis and induce holocrine secretion in human sebocytes

by Ann Don Low, Omkar Kulkarni, Francois Brillet, Eganathan Kaliyamoorthy, Angeline Tay, Scott Rice, Viduthalai Rasheedkhan Regina, and Tarun Chopra

Posted: September 24, 2026
Server: bioRxiv
DOI: 10.64898/2026.09.23.753677

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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PREreview by Prerna Mehta

Authored by Prerna Mehta

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…

Read the PREreview by Prerna Mehta
PREreview by Prerna Mehta

Authored by Prerna Mehta

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…

Read the PREreview by Prerna Mehta
PREreview by Prerna Mehta

Authored by Prerna Mehta

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…

Read the PREreview by Prerna Mehta