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Nutrients
Volume 17
Issue 15
10.3390/nu17152537
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Lacticaseibacillus paracasei L21 and Its Postbiotics Ameliorate Ulcerative Colitis Through Gut Microbiota Modulation, Intestinal Barrier Restoration, and HIF1α/AhR-IL-22 Axis Activation: Combined In Vitro and In Vivo Evidence

by
Jingru Chen
1,
Linfang Zhang
2,
Yuehua Jiao
3,
Xuan Lu
1,
Ning Zhang
1,
Xinyi Li
1,
Suo Zheng
1,
Bailiang Li
1,
Fei Liu
1,* and
Peng Zuo
4,*
1
Key Laboratory of Dairy Science, Ministry of Education, Food College, Northeast Agricultural University, Harbin 150030, China
2
Department of Grain Engineering, Heilongjiang Jiaotong Polytechnic, Harbin 161000, China
3
Center of Drug Safety Evaluation, Heilongjiang University of Chinese Medicine, Harbin 150040, China
4
College of Arts and Sciences, Northeast Agricultural University, Harbin 150030, China
*
Authors to whom correspondence should be addressed.
Nutrients 2025, 17(15), 2537; https://doi.org/10.3390/nu17152537 (registering DOI)
Submission received: 12 June 2025 / Revised: 26 July 2025 / Accepted: 31 July 2025 / Published: 1 August 2025
(This article belongs to the Special Issue Probiotics, Postbiotics, Gut Microbiota and Gastrointestinal Health)
Versions Notes

Abstract

Background: Ulcerative colitis (UC), characterized by chronic intestinal inflammation, epithelial barrier dysfunction, and immune imbalance demands novel ameliorative strategies beyond conventional approaches. Methods: In this study, the probiotic properties of Lactobacillus paracasei L21 (L. paracasei L21) and its ability to ameliorate colitis were evaluated using an in vitro lipopolysaccharide (LPS)-induced intestinal crypt epithelial cell (IEC-6) model and an in vivo dextran sulfate sodium (DSS)-induced UC mouse model. Results: In vitro, L. paracasei L21 decreased levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-8) while increasing anti-inflammatory IL-10 levels (p < 0.05) in LPS-induced IEC-6 cells, significantly enhancing the expression of tight junction proteins (ZO-1, occludin, claudin-1), thereby restoring the intestinal barrier. In vivo, both viable L. paracasei L21 and its heat-inactivated postbiotic (H-L21) mitigated weight loss, colon shortening, and disease activity indices, concurrently reducing serum LPS and proinflammatory mediators. Interventions inhibited NF-κB signaling while activating HIF1α/AhR pathways, increasing IL-22 and mucin MUC2 to restore goblet cell populations. Gut microbiota analysis showed that both interventions increased the abundance of beneficial gut bacteria (Lactobacillus, Dubococcus, and Akkermansia) and improved faecal propanoic acid and butyric acid levels. H-L21 uniquely exerted an anti-inflammatory effect, marked by the regulation of Dubosiella, while L. paracasei L21 marked by the Akkermansia. Conclusions: These results highlight the potential of L. paracasei L21 as a candidate for the development of both probiotic and postbiotic formulations. It is expected to provide a theoretical basis for the management of UC and to drive the development of the next generation of UC therapies.
Keywords: lactic acid bacteria; ulcerative colitis; gut microbiota; inflammatory cytokines; intestinal barrier lactic acid bacteria; ulcerative colitis; gut microbiota; inflammatory cytokines; intestinal barrier

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MDPI and ACS Style

Chen, J.; Zhang, L.; Jiao, Y.; Lu, X.; Zhang, N.; Li, X.; Zheng, S.; Li, B.; Liu, F.; Zuo, P. Lacticaseibacillus paracasei L21 and Its Postbiotics Ameliorate Ulcerative Colitis Through Gut Microbiota Modulation, Intestinal Barrier Restoration, and HIF1α/AhR-IL-22 Axis Activation: Combined In Vitro and In Vivo Evidence. Nutrients 2025, 17, 2537. https://doi.org/10.3390/nu17152537

AMA Style

Chen J, Zhang L, Jiao Y, Lu X, Zhang N, Li X, Zheng S, Li B, Liu F, Zuo P. Lacticaseibacillus paracasei L21 and Its Postbiotics Ameliorate Ulcerative Colitis Through Gut Microbiota Modulation, Intestinal Barrier Restoration, and HIF1α/AhR-IL-22 Axis Activation: Combined In Vitro and In Vivo Evidence. Nutrients. 2025; 17(15):2537. https://doi.org/10.3390/nu17152537

Chicago/Turabian Style

Chen, Jingru, Linfang Zhang, Yuehua Jiao, Xuan Lu, Ning Zhang, Xinyi Li, Suo Zheng, Bailiang Li, Fei Liu, and Peng Zuo. 2025. "Lacticaseibacillus paracasei L21 and Its Postbiotics Ameliorate Ulcerative Colitis Through Gut Microbiota Modulation, Intestinal Barrier Restoration, and HIF1α/AhR-IL-22 Axis Activation: Combined In Vitro and In Vivo Evidence" Nutrients 17, no. 15: 2537. https://doi.org/10.3390/nu17152537

APA Style

Chen, J., Zhang, L., Jiao, Y., Lu, X., Zhang, N., Li, X., Zheng, S., Li, B., Liu, F., & Zuo, P. (2025). Lacticaseibacillus paracasei L21 and Its Postbiotics Ameliorate Ulcerative Colitis Through Gut Microbiota Modulation, Intestinal Barrier Restoration, and HIF1α/AhR-IL-22 Axis Activation: Combined In Vitro and In Vivo Evidence. Nutrients, 17(15), 2537. https://doi.org/10.3390/nu17152537

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