Bioactive Low-Molecular-Weight Fraction from Limosilactobacillus fermentum CECT5716 Attenuates Intestinal Inflammation and Dysbiosis in DSS-Treated Mice

Gbati, Luckman; Rodríguez-Sojo, María Jesús; Molina-Tijeras, Jose Alberto; García-García, Jorge; López-Escánez, Laura; Vezza, Teresa; Ruiz-Malagon, Antonio Jesús; Bouraïma, Djeri; García, Federico; Gálvez, Julio; Rodríguez-Nogales, Alba; Rodríguez-Cabezas, María Elena

doi:10.3390/nu18121890

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Bioactive Low-Molecular-Weight Fraction from Limosilactobacillus fermentum CECT5716 Attenuates Intestinal Inflammation and Dysbiosis in DSS-Treated Mice

by

Luckman Gbati

^1,2,3,†

,

María Jesús Rodríguez-Sojo

^1,2,†,

Jose Alberto Molina-Tijeras

^1,2,3,*

,

Jorge García-García

^2,4

,

Laura López-Escánez

^1,2,

Teresa Vezza

^2,5

,

Antonio Jesús Ruiz-Malagon

^1,2,*

,

Djeri Bouraïma

⁶,

Federico García

^2,4,7

,

Julio Gálvez

^1,2,8

,

Alba Rodríguez-Nogales

^1,2,‡

and

María Elena Rodríguez-Cabezas

^1,2,‡

¹

Department of Pharmacology, Center for Biomedical Research (CIBM), University of Granada, 18071 Granada, Spain

²

Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012 Granada, Spain

³

Department of Health, Medicine and Life Sciences, Faculty of Science, Technology and Medicine, University of Luxembourg, 4367 Esch-sur-Alzette, Luxembourg

⁴

Servicio de Microbiología, Hospital Universitario San Cecilio, 18007 Granada, Spain

⁵

Servicio de Digestivo, Hospital Universitario Virgen de las Nieves, 18012 Granada, Spain

⁶

Microbiology and Food Quality Control Laboratory (LAMICODA), Higher School of Biological and Food Techniques (ESTBA), University of Lomé, Lomé 01 BP 1515, Togo

⁷

CIBER-Enfermedades Infecciosas (CIBER-Infecc), Instituto de Salud Carlos III, 28029 Madrid, Spain

⁸

CIBER-Enfermedades Hepáticas y Digestivas (CIBER-EHD), Instituto de Salud Carlos III, 28029 Madrid, Spain

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

These authors contributed equally to the supervision of the study.

Nutrients 2026, 18(12), 1890; https://doi.org/10.3390/nu18121890

Submission received: 9 April 2026 / Revised: 8 June 2026 / Accepted: 10 June 2026 / Published: 11 June 2026

(This article belongs to the Special Issue Effects of Probiotics, Prebiotics, and Postbiotics on Human Health (3rd Edition))

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Abstract

Background: Postbiotics, including cell-free supernatants and their fractions, have emerged as a safe and effective alternative to live probiotics for managing intestinal inflammation. This study investigated the protective effects of low-molecular-weight fractions (<3 kDa) of the probiotic Limosilactobacillus fermentum CECT5716 (LMW-LF) in a murine model of experimental colitis. Methods: Male C57BL/6J mice were orally administered LMW-LF for 10 days prior to colitis induction with 3% dextran sodium sulfate (DSS) for 5 days. Colonic damage was assessed via the Disease Activity Index (DAI), histology, and immunofluorescence (Ocln and Ki67). Immune cell populations were analyzed by flow cytometry, while mucosal gene expression and gut microbiota composition were evaluated using RT-qPCR and 16S rRNA sequencing, respectively. Results: LMW-LF administration significantly attenuated clinical symptoms and macroscopic colonic damage. Treatment restored epithelial barrier integrity by upregulating tight junction proteins (Tjp1) and mucin genes (Muc1-3) while normalizing DSS-induced epithelial hyperproliferation. Immunologically, LMW-LF reduced pro-inflammatory monocyte infiltration; downregulated Il6, Tnfa, and Ifng; and promoted an immunoregulatory phenotype by enhancing Ampk expression and partially restoring regulatory T cell (Treg) populations. Furthermore, LMW-LF reshaped the gut microbiota by increasing alpha diversity and promoting the enrichment of beneficial taxa, specifically Akkermansia muciniphila, which correlated with improved mucus layer preservation. Conclusions: LMW-LF is an active fraction acting across the host–microbiota axis. By integrating epithelial protection, immunomodulation, and microbial reshaping, it represents a promising dietary strategy for the management of Inflammatory Bowel Diseases.

Keywords: Limosilactobacillus fermentum CECT5716; postbiotics; DSS-induced colitis; intestinal barrier; gut microbiota; immunomodulation

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MDPI and ACS Style

Gbati, L.; Rodríguez-Sojo, M.J.; Molina-Tijeras, J.A.; García-García, J.; López-Escánez, L.; Vezza, T.; Ruiz-Malagon, A.J.; Bouraïma, D.; García, F.; Gálvez, J.; et al. Bioactive Low-Molecular-Weight Fraction from Limosilactobacillus fermentum CECT5716 Attenuates Intestinal Inflammation and Dysbiosis in DSS-Treated Mice. Nutrients 2026, 18, 1890. https://doi.org/10.3390/nu18121890

AMA Style

Gbati L, Rodríguez-Sojo MJ, Molina-Tijeras JA, García-García J, López-Escánez L, Vezza T, Ruiz-Malagon AJ, Bouraïma D, García F, Gálvez J, et al. Bioactive Low-Molecular-Weight Fraction from Limosilactobacillus fermentum CECT5716 Attenuates Intestinal Inflammation and Dysbiosis in DSS-Treated Mice. Nutrients. 2026; 18(12):1890. https://doi.org/10.3390/nu18121890

Chicago/Turabian Style

Gbati, Luckman, María Jesús Rodríguez-Sojo, Jose Alberto Molina-Tijeras, Jorge García-García, Laura López-Escánez, Teresa Vezza, Antonio Jesús Ruiz-Malagon, Djeri Bouraïma, Federico García, Julio Gálvez, and et al. 2026. "Bioactive Low-Molecular-Weight Fraction from Limosilactobacillus fermentum CECT5716 Attenuates Intestinal Inflammation and Dysbiosis in DSS-Treated Mice" Nutrients 18, no. 12: 1890. https://doi.org/10.3390/nu18121890

APA Style

Gbati, L., Rodríguez-Sojo, M. J., Molina-Tijeras, J. A., García-García, J., López-Escánez, L., Vezza, T., Ruiz-Malagon, A. J., Bouraïma, D., García, F., Gálvez, J., Rodríguez-Nogales, A., & Rodríguez-Cabezas, M. E. (2026). Bioactive Low-Molecular-Weight Fraction from Limosilactobacillus fermentum CECT5716 Attenuates Intestinal Inflammation and Dysbiosis in DSS-Treated Mice. Nutrients, 18(12), 1890. https://doi.org/10.3390/nu18121890

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Bioactive Low-Molecular-Weight Fraction from Limosilactobacillus fermentum CECT5716 Attenuates Intestinal Inflammation and Dysbiosis in DSS-Treated Mice

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