Abstract Background Lauric acid (LA), a medium-chain fatty acid with reported anti-inflammatory properties, has a poorly defined role in inflammatory bowel disease (IBD), particularly regarding intestinal fibrosis. We previously demonstrated that LA exerts antifibrotic effects in intestinal fibroblasts (Patel et al., 2025), but its impact on human smooth intestinal muscle cells (HSIMCs)—key contributors to intestinal fibrogenesis—remains unknown. Methods The aim of this study was to determine whether lauric acid exerts antifibrotic effects in HSIMCs and to identify the receptors involved in this response. HSIMCs were stimulated with LA (0–250 nM) under basal or pro-fibrotic conditions (TGFβ1, 10 ng/mL). Fibrotic markers and potential LA-responsive receptors (GPR84, TLR4, TLR2, PPARγ, PPARα, and TRPV1) were quantified by qPCR. Data are presented as fold change (mean ± SEM) relative to 0 nM LA and analyzed using parametric ANOVA or non-parametric Kruskal–Wallis tests, as appropriate (*P 0.05 vs. 0 nM LA; **P 0.01; #P 0.05 vs. 0 nM LA + TGFβ1; ##P 0.01). Results Lauric acid effectively counteracted the profibrotic response induced by TGFβ1 in HSIMCs, preventing their transition into a myofibroblast-like phenotype. At increasing concentrations—particularly 250 µM—LA reduced the expression of Vimentin, α-SMA (ACTA2), and FSP1 (S100A4) while restoring Desmin levels (Figure 1A). Consistently, additional fibrotic markers—including COL1A1, COL3A1, and FNDC4—were also decreased under profibrotic stimulation, confirming the antifibrotic activity of LA (Figure 1B). In contrast, under non-profibrotic conditions (Figure 1C), LA induced a pro-inflammatory and tissue-remodeling profile in HSIMCs, increasing the expression of IL1B and VEGF. This dual behavior was mirrored in receptor regulation: LA strongly upregulated TLR4 under both basal and TGFβ1-stimulated conditions (250 nM: 7.5 ± 2.2* and 5.2 ± 1.1#, respectively), whereas PPARγ responded only under profibrotic stimulation (250 µM: 1.6 ± 0.3*). Conclusion These findings indicate that lauric acid modulates HSIMC behavior in a context-dependent manner. Under profibrotic stimulation, LA activates antifibrotic pathways that prevent myofibroblast differentiation. In contrast, under basal conditions, LA induces a mild pro-inflammatory and remodeling response, which may reflect an early protective signal that limits fibrotic activation when profibrotic cues are absent. Overall, LA appears to balance inflammatory and antifibrotic signals depending on the cellular environment. Reference: Patel J, Cejudo-Garcés A, Jarén A, Macias-Ceja D C, López A, Manresa M, Calatayud S, Barrachina M D, Cosín-Roger J, Ortiz-Masiá D. “P0164 Lauric Acid in Inflammatory Bowel Disease: Balancing Fibrosis Modulation and Epithelial–Mesenchymal Transition Activation.” Journal of Crohn’s and Colitis. 2025;19(Suppl 1):i562. doi:10.1093/ecco-jcc/jjae190.0338. Conflict of interest: Patel, Jalpa: No conflict of interest Cejudo-Garcés, Andrea: No conflict of interest Jarén, Ana: Nothing to disclouse Cosín-Roger, Jesús: No conflict of interest Prof. Dr. Ortiz-Masiá, Dolores: No conflict of interest
Patel et al. (Thu,) studied this question.