Combined Lacticaseibacillus rhamnosus-Derived Lysate and Cannabis spp. Extracts Enhance Epithelial Restitution in a Caco-2 Wound Healing Model

Intestinal epithelial integrity underpins gastrointestinal homeostasis, and its disruption is associated with dysbiosis, inflammation, and impaired barrier function. Postbiotic fractions derived from probiotic bacteria and plant bioactive compounds are increasingly investigated as candidates for functional food strategies aimed at promoting mucosal repair - yet their combined effects remain largely unexplored.

We examined how a protein-enriched lysate/supernatant from Lacticaseibacillus rhamnosus DSM 20711, alone and together with ethanolic Cannabis spp. extracts influence re-epithelialization in a standardised Caco-2 wound-healing model. Confluent monolayers were grown using Ibidi culture inserts; after insert removal, cells were exposed to Cannabis extracts (3.25, 7.5, or 15 µg/mL) with or without L. rhamnosus lysate/supernatant (6.25%). Gap closure was tracked over 92 h by time-lapse confocal imaging (Echo microscope, 37 °C, 5% CO₂, 8 h intervals), and residual wound area was quantified in Image-Pro v11.

Combined treatments enhanced wound closure compared with both the untreated control and either component applied alone. The response was non-linear: the two lower extract concentrations (3.25 and 7.5 µg/mL) elicited the most pronounced pro-migratory effect, reducing the remaining wound area by up to 50% relative to controls within the 48–64 h window, whereas the highest concentration was markedly less active.

Taken together, these data point to a potentially beneficial interaction between Cannabis spp. bioactives and L. rhamnosus-derived postbiotics in supporting epithelial barrier restoration, with implications for both functional food development and microbiome-targeted therapeutic strategies.

This research was funded by the METROFOOD-CZ Research Infrastructure Project (MEYS grant number: LM2023064).