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Volume 14
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10.3390/microorganisms14040931
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Article

New Postbiotic Derived from Sequential Fermentation of Two Lacticaseibacillus Strains Exerts Beneficial Effects on Epithelial Gut Barrier and Innate Immunity in Human Enterocytes

by
Franca Oglio
1,2,3,4,*,
Alessia Cadavere
1,2,3,4,
Monia De Aloe
1,2,3,4,
Anna Lintura
1,2,3,4,
Marco Michelini
1,2,3,4,
Chiara Luongo
1,2,3,4,
Serena Coppola
1,2,3,4,
Alessandra Agizza
1,2,3,4,
Erika Caldaria
1,2,3,4 and
Laura Carucci
1,2,3,4
1
Department of Translational Medical Science, University of Naples Federico II, 80131 Naples, Italy
2
ImmunoNutritionLab, CEINGE Biotecnologie Avanzate Franco Salvatore, 80131 Naples, Italy
3
NutriTechLab Academic Spin-Off, University of Naples Federico II, 80131 Naples, Italy
4
Task Force for Microbiome Studies, University of Naples Federico II, 80131 Naples, Italy
*
Author to whom correspondence should be addressed.
Microorganisms 2026, 14(4), 931; https://doi.org/10.3390/microorganisms14040931
Submission received: 27 February 2026 / Revised: 15 April 2026 / Accepted: 16 April 2026 / Published: 20 April 2026
(This article belongs to the Special Issue Interactions Between Probiotics and Host)
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Abstract

The efficacy of postbiotics varies significantly between different strains and preparation processes. We aimed at evaluating the effect of an innovative postbiotic product (iPB) generated through the sequential fermentation of Lacticaseibacillus rhamnosus GG and Lacticaseibacillus paracasei NPB-01, compared to single-strain postbiotics, on epithelial barrier integrity and innate immunity in human enterocytes using a Caco-2-cell-based experimental model by measuring human enterocyte proliferation and differentiation (lactase expression), tight junction proteins (occludin and zonula occludens 1, ZO-1), and mucus protein Mucin-2 (Muc-2) expression. The modulatory action on the major innate immunity peptide, Human Beta-Defensin 2 (HBD-2), production was also assessed. The iPB exposure resulted in a higher up-regulation of human enterocyte proliferation and differentiation, as suggested by higher lactase expression, and of occludin, ZO-1, and MUC2 expression compared with the single-strain postbiotics, suggesting a beneficial synergistic action in modulating the epithelial gut barrier. Furthermore, iPB induced a higher production of HBD-2, suggesting a synergistic enhancement of innate immune response. Our findings suggested that the sequential fermentation process could act as a biotechnological catalyst, optimizing the gut-barrier-protective properties and the immunomodulatory action of Lacticaseibacillus strains. This study introduces iPB as a high-performance postbiotic candidate for the prevention and management of conditions characterized by alterations in epithelial gut barrier and innate immunity.
Keywords: postbiotic; cell proliferation; tight junction proteins; occludin; zonula occludens 1; mucus protein Mucin-2; lactase; human beta-defensin 2 postbiotic; cell proliferation; tight junction proteins; occludin; zonula occludens 1; mucus protein Mucin-2; lactase; human beta-defensin 2

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MDPI and ACS Style

Oglio, F.; Cadavere, A.; De Aloe, M.; Lintura, A.; Michelini, M.; Luongo, C.; Coppola, S.; Agizza, A.; Caldaria, E.; Carucci, L. New Postbiotic Derived from Sequential Fermentation of Two Lacticaseibacillus Strains Exerts Beneficial Effects on Epithelial Gut Barrier and Innate Immunity in Human Enterocytes. Microorganisms 2026, 14, 931. https://doi.org/10.3390/microorganisms14040931

AMA Style

Oglio F, Cadavere A, De Aloe M, Lintura A, Michelini M, Luongo C, Coppola S, Agizza A, Caldaria E, Carucci L. New Postbiotic Derived from Sequential Fermentation of Two Lacticaseibacillus Strains Exerts Beneficial Effects on Epithelial Gut Barrier and Innate Immunity in Human Enterocytes. Microorganisms. 2026; 14(4):931. https://doi.org/10.3390/microorganisms14040931

Chicago/Turabian Style

Oglio, Franca, Alessia Cadavere, Monia De Aloe, Anna Lintura, Marco Michelini, Chiara Luongo, Serena Coppola, Alessandra Agizza, Erika Caldaria, and Laura Carucci. 2026. "New Postbiotic Derived from Sequential Fermentation of Two Lacticaseibacillus Strains Exerts Beneficial Effects on Epithelial Gut Barrier and Innate Immunity in Human Enterocytes" Microorganisms 14, no. 4: 931. https://doi.org/10.3390/microorganisms14040931

APA Style

Oglio, F., Cadavere, A., De Aloe, M., Lintura, A., Michelini, M., Luongo, C., Coppola, S., Agizza, A., Caldaria, E., & Carucci, L. (2026). New Postbiotic Derived from Sequential Fermentation of Two Lacticaseibacillus Strains Exerts Beneficial Effects on Epithelial Gut Barrier and Innate Immunity in Human Enterocytes. Microorganisms, 14(4), 931. https://doi.org/10.3390/microorganisms14040931

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