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β-Sitosterol β-D-glucoside (BSSG) triggers intestinal inflammation in zebrafish and mouse models prior to neurodegeneration onset.

Overview

Authors: Francesca Terrin1, Sofia Faggin2,3, Edoardo Bizzotto1, Davide Santinello1, Silvia Cerantola2, Giuseppe Borsato4, Fabrizio Fabris4, Alessandro Scarso4, Rosario Licitra5, Graziano Guella6, Gabriele Sales1, Stefano Cagnin1,7, Laura Treu1, Luigi Bubacco1, Maria Cecilia Giron2, Nicoletta Plotegher1, Luisa Dalla Valle1
ORCID iDs: Luisa Dalla Valle
  1. Department of Biology, University of Padova, Via U. Bassi 58/B, 35131 Padua, Italy
  2. Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Largo Meneghetti 2, 35131 Padua, Italy
  3. Institute of Digestive Health Research (IRSD), INSERM U1022, INRAe, ENVT, Toulouse University, Toulouse, France
  4. Department of Molecular Science and Nanosystems, Università Ca’ Foscari Venezia, 30172 Mestre Venice, Italy
  5. Department of Veterinary Sciences, University of Pisa, 56124 Pisa, Italy
  6. Department of Biology, University of Trento, 38123 Trento, Italy
  7. CIR-Myo Myology Center, University of Padova, 35131 Padua, Italy
Institutions: University of Padua (Italy); Inserm (France); École Nationale Vétérinaire de Toulouse (France); Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (France); Institut de Recherche en Santé Digestive (France); Université de Toulouse (France); Ca' Foscari University of Venice (Italy); University of Pisa (Italy); University of Trento (Italy)
Journal: Journal of biomedical science, volume 33, issue 1, article 45
Dates: received 28 July 2025; accepted 26 April 2026; published online 4 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1186/s12929-026-01249-8 · PMID 42082968 · PMCID PMC13137512 · OpenAlex W7160053132
Open access: diamond, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism), zebrafish (organism), other condition (population), cellular / molecular (subfield)
Methods: Statistics, Evoked potentials, fMRI & imaging
Keywords: BSSG, Glucosylated sterols, Intestinal inflammation, Gut microbiota, Glucocorticoid receptor, Gut–brain axis, Zebrafish model, Mouse model
MeSH: Glucosides*, Inflammation*, Intestines*, Neurodegenerative Diseases*, Sitosterols*, Animals, Disease Models, Animal, Gastrointestinal Microbiome, Mice, Zebrafish (* major topic)
Topic: Cholesterol and Lipid Metabolism (Surgery, Medicine), according to OpenAlex
Funding: Department of Biology (PostDoc Fellowship 2024); Department of Pharmaceutical and Pharmacological Sciences (PostDoc Fellowship ARD-B 2020, PostDoc Fellowship ARD-B 2023); San Camillo Hospital Grant, Treviso, Italy (UNIPD-DSF-PRID-2023); Department of Biology Intramural Grant (Seed 2022, Seed 2020); MUR/University of Padova (PhD Fellowship 2020); National Center For Gene Therapy And Drugs Based On RNA Technology Neurodegeneration (Project ID: CN00000041 - SP. 3)
Citations: cited by 2 papers (Europe PMC); 79 references in the paper

Abstract

Background: Glucosylated-sterols can be synthetized endogenously, absorbed through the diet or derive from bacterial infection. Their clinical relevance is currently underestimated, even though their imbalance has been associated with an increased risk of neurodegeneration over the lifespan. We studied the detrimental effects elicited by dietary consumption of the plant-derived β-sitosterol β-d-glucoside (BSSG), known to be associated with the occurrence of ALS-PDC, to elucidate its potential mechanism of action.

Methods: Zebrafish larvae and adults, as well as mice, were treated with BSSG administered directly in the water or via customized food pellet, respectively. Since the intestine was identified as the primary target tissue, its morphological and functional characteristics were assessed, together with transcriptional profiling and gut microbiota sequencing. Ex vivo analysis of zebrafish gut contractility was applied to evaluate intestinal neuromuscular responses. Mutant and transgenic zebrafish lines were used to explore a potential BSSG mechanism of action.

Results: BSSG induced intestinal inflammation in both zebrafish and mouse models. This previously unknown effect was evidenced by gut dysmotility and inflammatory response. Transcriptomic analyses revealed increased expression of inflammation-related genes in the intestine of both zebrafish and mice, while preliminary gut microbiota analyses suggested the onset of dysbiosis. Transgenic and mutant zebrafish lines, depleted of genes involved in glucocorticoids synthesis and activity, evidenced that BSSG likely interacts with the glucocorticoid receptor, potentially impairing its canonical anti-inflammatory activity.

Conclusions: We identified novel pathways altered by dietary BSSG exposure. This molecule appears to initially induce gut inflammation, leading to changes in intestinal morphology and function, and may contribute to neurodegeneration through disruption of the well-known gut–brain axis.

Supplementary Information: The online version contains supplementary material available at 10.1186/s12929-026-01249-8.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

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Data

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Availability of data and materials

Transcriptional data generated during the current study have been deposited in SRA database (URL will be made available upon request). Other data supporting the findings of this study are available on reasonable request to the corresponding authors.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 17 authors, 8 keywords, 10 MeSH terms, 6 funders, 75 references.

Cite

This paper

Terrin, F., Faggin, S., Bizzotto, E., Santinello, D., Cerantola, S., Borsato, G., Fabris, F., Scarso, A., Licitra, R., Guella, G., Sales, G., Cagnin, S., Treu, L., Bubacco, L., Giron, M. C., Plotegher, N., & Dalla Valle, L. (2026). β-Sitosterol β-D-glucoside (BSSG) triggers intestinal inflammation in zebrafish and mouse models prior to neurodegeneration onset. Journal of biomedical science, 33(1), 45. https://doi.org/10.1186/s12929-026-01249-8

BibTeX

@article{terrin2026sitosterol,
author = {Terrin, Francesca and Faggin, Sofia and Bizzotto, Edoardo and Santinello, Davide and Cerantola, Silvia and Borsato, Giuseppe and Fabris, Fabrizio and Scarso, Alessandro and Licitra, Rosario and Guella, Graziano and Sales, Gabriele and Cagnin, Stefano and Treu, Laura and Bubacco, Luigi and Giron, Maria Cecilia and Plotegher, Nicoletta and Dalla Valle, Luisa},
title = {{β-Sitosterol β-D-glucoside (BSSG) triggers intestinal inflammation in zebrafish and mouse models prior to neurodegeneration onset}},
journal = {Journal of biomedical science},
year = {2026},
month = may,
volume = {33},
number = {1},
pages = {45},
publisher = {BMC},
issn = {1021-7770},
doi = {10.1186/s12929-026-01249-8},
url = {https://doi.org/10.1186/s12929-026-01249-8},
pmid = {42082968},
pmcid = {PMC13137512}
}

RIS

TY - JOUR
AU - Terrin, Francesca
AU - Faggin, Sofia
AU - Bizzotto, Edoardo
AU - Santinello, Davide
AU - Cerantola, Silvia
AU - Borsato, Giuseppe
AU - Fabris, Fabrizio
AU - Scarso, Alessandro
AU - Licitra, Rosario
AU - Guella, Graziano
AU - Sales, Gabriele
AU - Cagnin, Stefano
AU - Treu, Laura
AU - Bubacco, Luigi
AU - Giron, Maria Cecilia
AU - Plotegher, Nicoletta
AU - Dalla Valle, Luisa
TI - β-Sitosterol β-D-glucoside (BSSG) triggers intestinal inflammation in zebrafish and mouse models prior to neurodegeneration onset
T2 - Journal of biomedical science
J2 - J Biomed Sci
PY - 2026
DA - 2026/05/04
VL - 33
IS - 1
SP - 45
SN - 1021-7770
PB - BMC
DO - 10.1186/s12929-026-01249-8
UR - https://doi.org/10.1186/s12929-026-01249-8
LA - en
ER -

CSL-JSON

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