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Gut-brain axis: beneficial impact of Shouchella clausii spores on fructose induced dysfunction is associated with modulation of the deoxycholic acid - TGR5 pathway.

Overview

Authors: Maria Stefania Spagnuolo1, Natasha Petecca2, Francesca De Palma2, Antonio Dario Troise1, Angela Di Porzio2, Valentina Barrella2, Anella Saggese2, Sabrina De Pascale1, Marina De Stefano2, Andrea Scaloni1, Loredana Baccigalupi3,4,5, Ezio Ricca2, Susanna Iossa2,4,5, Arianna Mazzoli2, Luisa Cigliano2,5
  1. Institute for the Animal Production System in the Mediterranean Environment, National Research Council, P.Le Enrico Fermi 1, Portici, 80055 Italy
  2. Department of Biology, University of Naples Federico II, Complesso Universitario Monte S. Angelo, Edificio 7, Via Cintia, Naples, 80126 Italy
  3. Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via Pansini 5, Naples, 80100 Italy
  4. NBFC, National Biodiversity Future Center, Palermo, 90133 Italy
  5. Task Force On Microbiome Studies, University of Naples Federico II, Naples, 80126 Italy
Journal: Molecular medicine (Cambridge, Mass.), volume 32, issue 1, article 101
Dates: received 5 February 2026; accepted 6 April 2026; published online 9 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1186/s10020-026-01479-4 · PMID 42106599 · PMCID PMC13326143 · OpenAlex W7160692174
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: rat (organism), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions, Connectivity, fMRI & imaging
Keywords: Sugar, Probiotic, Inflammation, Brain, Bile acids, Synaptic function, Memory, Microbiota
MeSH: Actinobacteria*, Brain*, Brain-Gut Axis*, Deoxycholic Acid*, Fructose*, Probiotics*, Receptors, G-Protein-Coupled*, Animals, Gastrointestinal Microbiome, Male, Rats, Rats, Wistar, Signal Transduction (* major topic)
Topic: Diet, Metabolism, and Disease (Endocrinology, Diabetes and Metabolism, Medicine), according to OpenAlex
Funding: National Recovery and Resilience Plan, mission 4, component 2, investment 1.3, call n. 341/2022 of Italian Ministry of University and Research funded by the European Union - NextGenerationEU ("ON Foods - Research and innovation network on food and nutrition Sustainability, Safety and Security - Working ON Foods", project PE00000003, concession decree n. 1550/2022, CUP E63C22002030007, CUP B83C22004790001); University of Naples Federico II (Ricerca Dip 2023/2024); National Recovery and Resilience Plan, mission 4, Component C2, funded by the European Union - NextGenerationEU (PRIN 2022PNRR (P2022LTFLR))
Citations: cited by 1 paper (Europe PMC); 84 references in the paper

Abstract

Objective: The increased intake of added sweeteners, such as high-fructose corn syrup, has been associated with a rise in metabolic dysfunctions in gut and brain. While different evidence showed that dietary fructose induces gut microbiota reshaping, the sugar impact on specific bacteria-derived metabolites remains an understudied topic. In this study, we identified secondary bile acids (sBAs) as molecules differentially represented in plasma of rats fed a fructose-rich diet compared to control animals, and hypothesized that these metabolites might be a target for probiotic-based strategies to counteract sugar-induced metabolic disorders. To this aim, we investigated whether probiotic spores of Shouchella clausii SF174 ameliorate fructose-induced cognitive and metabolic dysfunctions and prevent molecular alterations in hippocampus and frontal cortex.

Methods: Wistar rats were fed a fructose-rich diet, alone or in combination with the daily administration of Shouchella clausii spores, for six weeks. At the end of treatment, behavioral, metabolomic and molecular analyses were performed.

Results: The probiotic spores exerted a protective effect on the memory function of fructose fed rats and prevented the decrease of markers of synaptic plasticity. This was associated with the maintenance of plasma and brain levels of the sBA deoxycholic acid and of its specific receptor Takeda G protein-coupled receptor 5. Further, spores beneficial modulation of fructose-induced peripheral and central inflammation was observed. Also, probiotic spores produced reshaping of the gut microbiota towards a composition exerting neuroprotective and anti-inflammatory effects.

Conclusion: These results suggest that sBAs might act as a communication bridge along the microbiota gut-brain axis and suggest that their modulation, through probiotic administration, represents an effective strategy to counteract fructose-induced neuroinflammation and gut-brain dysfunction.

Supplementary Information: The online version contains supplementary material available at 10.1186/s10020-026-01479-4.

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

Code

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Data

Datasets cited

Data availability

The data used and/or analyzed in this study are available from the corresponding author upon reasonable request.

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, 15 authors, 8 keywords, 13 MeSH terms, 3 funders, 84 references.

Cite

This paper

Spagnuolo, M. S., Petecca, N., De Palma, F., Troise, A. D., Di Porzio, A., Barrella, V., Saggese, A., De Pascale, S., De Stefano, M., Scaloni, A., Baccigalupi, L., Ricca, E., Iossa, S., Mazzoli, A., & Cigliano, L. (2026). Gut-brain axis: beneficial impact of Shouchella clausii spores on fructose induced dysfunction is associated with modulation of the deoxycholic acid - TGR5 pathway. Molecular medicine (Cambridge, Mass.), 32(1), 101. https://doi.org/10.1186/s10020-026-01479-4

BibTeX

@article{spagnuolo2026gut,
author = {Spagnuolo, Maria Stefania and Petecca, Natasha and De Palma, Francesca and Troise, Antonio Dario and Di Porzio, Angela and Barrella, Valentina and Saggese, Anella and De Pascale, Sabrina and De Stefano, Marina and Scaloni, Andrea and Baccigalupi, Loredana and Ricca, Ezio and Iossa, Susanna and Mazzoli, Arianna and Cigliano, Luisa},
title = {{Gut-brain axis: beneficial impact of Shouchella clausii spores on fructose induced dysfunction is associated with modulation of the deoxycholic acid - TGR5 pathway}},
journal = {Molecular medicine (Cambridge, Mass.)},
year = {2026},
month = may,
volume = {32},
number = {1},
pages = {101},
publisher = {The Feinstein Institute for Medical Research},
issn = {1076-1551},
doi = {10.1186/s10020-026-01479-4},
url = {https://doi.org/10.1186/s10020-026-01479-4},
pmid = {42106599},
pmcid = {PMC13326143}
}

RIS

TY - JOUR
AU - Spagnuolo, Maria Stefania
AU - Petecca, Natasha
AU - De Palma, Francesca
AU - Troise, Antonio Dario
AU - Di Porzio, Angela
AU - Barrella, Valentina
AU - Saggese, Anella
AU - De Pascale, Sabrina
AU - De Stefano, Marina
AU - Scaloni, Andrea
AU - Baccigalupi, Loredana
AU - Ricca, Ezio
AU - Iossa, Susanna
AU - Mazzoli, Arianna
AU - Cigliano, Luisa
TI - Gut-brain axis: beneficial impact of Shouchella clausii spores on fructose induced dysfunction is associated with modulation of the deoxycholic acid - TGR5 pathway
T2 - Molecular medicine (Cambridge, Mass.)
J2 - Mol Med
PY - 2026
DA - 2026/05/09
VL - 32
IS - 1
SP - 101
SN - 1076-1551
PB - The Feinstein Institute for Medical Research
DO - 10.1186/s10020-026-01479-4
UR - https://doi.org/10.1186/s10020-026-01479-4
LA - en
ER -

CSL-JSON

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