Improving skin barrier by enhancing function of Tight junctions

Improving skin barrier by enhancing function of Tight junctions

Probiotic lysates from certain bacterial strains can enhance tight-junction function in human keratinocytes, with Bifidobacterium longum and Lactobacillus rhamnosus GG being the most effective, potentially through modulation of protein components.

Reshma Sultana and colleagues (2013) described strain-dependent augmentation of tight-junction barrier function in human primary epidermal keratinocytes by lactobacillus and Bifidobacterium lysates. Probiotic lysates, specifically from B. longum, can enhance tight junction function in human primary keratinocytes through signaling via Toll Like Receptor-2 (TLR2). The potential of bacterially derived components to improve tight junction function in keratinocytes is demonstrated, with ramifications for conditions like atopic dermatitis. Tight junctions are crucial for skin barrier function, and probiotic lysates may play a role in treating barrier dysfunction. The use of lysates from probiotic bacteria is preferred for skin health due to their safety record.

WHAT THIS ARTICLE ADDS:

the study investigated whether probiotic lysates can modify the tight-junction function of human primary keratinocytes

  • The mechanism by which  B. longum  increases tight junctions (TJs) protein expression and transepithelial electrical resistance (TEER) is almost certainly associated with signaling through Toll Like Receptor-2 (TLR2)
  • The peptidoglycan-induced increase in TJ function was Toll-like receptors (TLRs) dependent. All these data demonstrate the potential for bacterial lysate to augment TJ function in keratinocytes.
  • It may be that some of the molecular mechanisms used by probiotic bacteria such as L. rhamnosus GG to increase TJ function are similar between gut and skin.
  • Currently, virtually nothing is known regarding how TJs are formed or regulated in skin, so much more work is required in the area before firm conclusions can be reached as to how the L. rhamnosus GG lysate enhances keratinocyte TJ barrier function
  • Lysates of probiotic bacteria could potentially play a role in the treatment of barrier dysfunction under conditions where the TJs are known to be aberrant, such as atopic dermatitis, where loss of expression of claudin 1 is reportedly involved in a subset of patients.

ABSTRACT

In this study, the authors investigated whether probiotic lysates can modify the tight-junction function of human primary keratinocytes. The keratinocytes were grown on cell culture inserts and treated with lysates from Bifidobacterium longum, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus fermentum, or Lactobacillus rhamnosus GG. With the exception of L. fermentum (which decreased cell viability), all strains markedly enhanced tight-junction barrier function within 24 h, as assessed by measurements of transepithelial electrical resistance (TEER). However, B. longum and L. rhamnosus GG were the most efficacious, producing dose-dependent increases in resistance that were maintained for 4 days. These increases in TEER correlated with elevated expression of tight-junction protein components. Neutralization of Toll-like receptor 2 abolished both the increase in TEER and expression of tight-junction proteins induced by B. longum, but not L. rhamnosus GG. These data suggest that some bacterial strains increase tight-junction function via modulation of protein components but the different pathways involved may vary depending on the bacterial strain.

KEY RESULTS

  • Five strains of bacteria were evaluated for their effect on TJ function. Of these, lysates of all but L. fermentum were able to increase the TEER of keratinocytes. L. The other four strains of lactobacilli all enhanced TJ function, but to different degrees. In this regard, L. rhamnosus GG and B. longum produced greater and more sustained increases in TEER than did L. plantarum or L. reuteri.
  • Peptidoglycan also induced increased transepithelial electrical resistance (TEER) in keratinocytes. However, the changes observed were strikingly different from those seen with whole lysates.  Nevertheless, this raises the interesting possibility that cell wall components in the lysates may be at least partially responsible for the changes observed in TJ function. However, the significant differences between the effects of peptidoglycan and lysates, and the differential effects of lysates derived from specific strains, suggest that molecules specific to individual bacteria have different efficacies in enhancing barrier function.
  • Both L. rhamnosus GG and B. longum increased the expression of TJ proteins in keratinocytes. However, the particular subset of molecules was different in each case. 
  •  The modulation of protein expression by B. longum and L. rhamnosus GG is almost certainly the mechanism by which lysates of increase the TJ barrier function of keratinocytes. Changes in the expression levels of claudins in particular have been shown many times previously to be linked to changes in barrier function. Furthermore, the human skin disease atopic dermatitis, where the barrier is aberrant, is known to be associated with reduced claudin 1 expression. Hence, the evidence in skin so far suggests that expression of TJ proteins is associated with barrier function.

FINDINGS

Lysates of probiotic bacteria could potentially play a role in the treatment of barrier dysfunction under conditions where the TJs are known to be aberrant, such as atopic dermatitis, where loss of expression of claudin 1 is reportedly involved in a subset of patients.

Sultana, R., McBain, A. J., & O’Neill, C. A. (2013). Strain-Dependent Augmentation of Tight-Junction Barrier Function in Human Primary Epidermal Keratinocytes by Lactobacillus and Bifidobacterium Lysates. Applied and Environmental Microbiology, 79(16), 4887–4894. https://doi.org/10.1128/aem.00982-13

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