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. 2024 Jan 2;12(1):2184157.
doi: 10.1080/21688370.2023.2184157. Epub 2023 Feb 28.

Yogurt starter strains ameliorate intestinal barrier dysfunction via activating AMPK in Caco-2 cells

Kyosuke Kobayashi  1 , Junko Mochizuki  1 , Fuka Yamazaki  1 , Toshihiro Sashihara  1
Affiliations

Yogurt starter strains ameliorate intestinal barrier dysfunction via activating AMPK in Caco-2 cells

Kyosuke Kobayashi et al. Tissue Barriers. .

Abstract

Lactic acid bacteria (LAB) are commonly used probiotics that improve human health in various aspects. We previously reported that yogurt starter strains, Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131, potentially enhance the intestinal epithelial barrier function by inducing the expression of antimicrobial peptides in the small intestine. However, their effects on physical barrier functions remain unknown. In this study, we found that both strains ameliorated the decreased trans-epithelial resistance and the increased permeability of fluorescein isothiocyanate-dextran induced by tumor necrosis factor (TNF)-α and interferon (IFN)-γ in Caco-2 cells. We also demonstrated that LAB prevented a decrease in the expression and disassembly of tight junctions (TJs) induced by TNF-α and IFN-γ. To assess the repair activity of TJs, a calcium switch assay was performed. Both strains were found to promote the reassembly of TJs, and their activity was canceled by the inhibitor of AMP-activated protein kinase (AMPK). Moreover, these strains showed increased AMPK phosphorylation. These observations suggest that the strains ameliorated physical barrier dysfunction via the activation of AMPK. The activities preventing barrier destruction induced by TNF-α and IFN-γ were strain-dependent. Several strains containing L. bulgaricus 2038 and S. thermophilus 1131 significantly suppressed the barrier impairment, and L. bulgaricus 2038 showed the strongest activity among them. Our findings suggest that the intake of L. bulgaricus 2038 and S. thermophilus 1131 is a potential strategy for the prevention and repair of leaky gut.

Keywords: AMPK; Lactobacillus delbrueckii subsp. bulgaricus; Streptococcus thermophilus; calcium switch assay; intestinal barrier function; tight junction.

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Conflict of interest statement

All authors are employees of Meiji Co. Ltd.

Figures

Figure 1.
Figure 1.
Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 improved the intestinal barrier dysfunction by tumor necrosis factor (TNF)-α and interferon (IFN)-γ.
Figure 2.
Figure 2.
L. bulgaricus 2038 and S. thermophilus 1131 suppressed the decrease in the gene expression levels of tight junctions (TJs) by TNF-α and IFN-γ.
Figure 3.
Figure 3.
L. bulgaricus 2038 and S. thermophilus 1131 suppressed the destruction of TJ proteins by TNF-α and IFN-γ.
Figure 4.
Figure 4.
L. bulgaricus 2038 and S. thermophilus 1131 promoted the assembly of TJ proteins in a calcium switch assay.
Figure 5.
Figure 5.
L. bulgaricus 2038 and S. thermophilus 1131 increased the expression of p-AMPK.
Figure 6.
Figure 6.
Protective effect on FD-4 permeability increased by TNF-α and IFN-γ was strain-dependent.
See this image and copyright information in PMC

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