Role of Lactiplantibacillus plantarum UBLP-40, Lactobacillus rhamnosus UBLR-58 and Bifidobacterium longum UBBL-64 in the Wound Healing Process of the Excisional Skin

Abstract

The probiotics Lactiplantibacillus plantarum UBLP-40, Lactobacillus rhamnosus UBLR-58 and Bifidobacterium longum UBBL-64 seem to promote wound healing when applied topically. Our aim was to investigate their effect on the mRNA expression of pro-inflammatory, healing and angiogenetic factors during the healing process of a standardized excisional wound model in rats. Rats subjected to six dorsal skin wounds were allocated to Control; L. plantarum; combined formula of L. rhamnosus plus B. longum; L. rhamnosus; and B. longum treatments, applied every two days, along with tissue collection. The pro-inflammatory, wound-healing, and angiogenetic factors of mRNA expression were assessed by qRT-PCR. We found that L. plantarum exerts a strong anti-inflammatory effect in relation to L. rhamnosus–B. longum, given alone or in combination; the combined regime of L. rhamnosus–B. longum, works better, greatly promoting the expression of healing and angiogenic factors than L. plantarum. When separately tested, L. rhamnosus was found to work better than B. longum in promoting the expression of healing factors, while B. longum seems stronger than L. rhamnosus in the expression of angiogenic factors. We, therefore, suggest that an ideal probiotic treatment should definitively contain more than one probiotic strain to speed up all three healing phases.

Looking for the Ideal Probiotic Healing Regime

“…Probiotics seem to work toward that end in two steps: L. plantarum spp., as the USM8613, MTCC 2621, SGL07, and UBLP-40 have been recognized in many studies as being that which has the strongest anti-inflammatory action, not only by means of significantly up-regulating the pro-inflammatory factors IL-1β, IL-4, IL-6, IFN-γ, β-defensin and the mRNA expression of CXCL10 and CXCL8, which are seriously involved in neutrophil and macrophage recruitment, but also by earlier down-regulating IL-8, IL-6, MCP-1, and RANTES and up-regulating the anti-inflammatory IL-10 and others. These actions clearly document their marked anti-inflammatory effect, which is possibly involved in the reduction of hypertrophic wound scar formation [19,20,33,38,41]. Furthermore, earlier experiments, having documented a faster wound closure during the inflammatory phase (days 1 to 4), clearly suggested the anti-inflammatory properties of probiotics [18,34,35].…”

“…Thus, it resulted in a mild but statistically significant induction of collagen type III mRNA expression from day 2 while reducing the TGF-β expression on day 8 compared to controls. In parallel, it up-regulated the EGF mRNA throughout the study period and down-regulated the VEGF mRNA up to day 8 in relation to controls [19].…”

“…Regarding wound healing response, B. longum exerts a significantly increased mRNA expression of TGF-β and α-SMA but a less profound up-regulation of collagen type III mRNA expression compared to L. plantarum. However, it generally seems stronger in promoting the expression of angiogenic factors compared to L. rhamnosus since it significantly up-regulates EGF and VEGF mRNA expression; however, it also exhibits significantly higher values in VEGF mRNA expression in relation to L. plantarum up to day 4 and down-regulates thereafter [19].…”

“…The topical effect of L. rhamnosus UBLR-58 regarding the mRNA expression of proinflammatory, healing, and angiogenetic factors involved in the healing process in relation to L. plantarum UBLP-40 was recently investigated on a standardized excisional wound in rats [19]. A statistically significant increase in the expression of IL-1β on days 2 and 15 and of IL-6 throughout the 14 d healing period compared to L. plantarum was found, which supports the hypothesis that L. rhamnosus exerts a less active role in the progression of the inflammatory phase compared to L. plantarum.…”

“…However, it is very difficult to assess the precise involvement of probiotics or postbiotics in the healing process since each strain has separate, distinctive, and even multi-factorial features of action [16,17]. With this knowledge, and given that a multi-probiotic formula exerts better results than a single strain [16,[18][19][20], although there are references to the opposite [21][22][23], the pharmaceutical industry has embarked on a race to produce a complex formulation containing a combination of probiotics, capable not only of modulating all the healing phases but also without the one probiotic inhibiting the action of the other [19,20,[24][25][26]. Hence, the object of this review is to describe what is known to date of the distinctive and even multi-factorial "healing" mechanisms of each probiotic strain in order to further facilitate research for the development of combinations of strains and doses covering the whole spectrum of healing.…”