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This research has been funded by the State Research Agency of the Spanish Ministry of Science and Innovation (PID2020-119116RA-I00, PID2020-113812RB-C32 and PID2021-126445OB-I00) , and by the Gobierno de Espana MCIN/AEI/10.13039/501100011033 and Union Europea "Next Generation EU"/PRTR (PDC2021-121248-I00, PLEC2021-007774 and CPP2022-009967) .

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Cabre, MariaAuthorGuardia-Escote, LaiaAuthor
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Exploring microbiota-gut-brain axis biomarkers linked to autism spectrum disorder in prenatally chlorpyrifos-exposed Fmr1 knock-out and wild-type male rats

Publicated to:Toxicology. 506 153871- - 2024-08-01 506(), DOI: 10.1016/j.tox.2024.153871

Authors: Salmeron, Ana M; Perez-Fernandez, Cristian; Abreu, Ana C; Fernandez, Silvia; Tristan, Ana I; Ruiz-Sobremazas, Diego; Cabre, Maria; Guardia-Escote, Laia; Fernandez, Ignacio; Sanchez-Santed, Fernando

Affiliations

Univ Almeria, Dept Psychol, Ctra Sacramento S-N, Almeria 04120, Spain - Author
Univ Almeria, Hlth Res Ctr, Res Ctr Social Welf & Inclus CIBIS, Ctra Sacramento S-N, Almeria 04120, Spain - Author
Univ Almeria, Res Ctr CIAIMBITAL, Dept Chem & Phys, Almeria, Spain - Author
Univ Rovira i Virgili, Dept Biochem & Biotechnol, Tarragona, Spain - Author
Univ Rovira i Virgili, Dept Psychol, Tarragona, Spain - Author
Univ Rovira i Virgili, Res Ctr Behav Assessment CRAMC, Tarragona, Spain - Author
Univ Rovira i Virgili, Res Grp Neurobehav & Hlth NEUROLAB, Tarragona, Spain - Author
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Abstract

Fmr1 (fragile X messenger ribonucleoprotein 1)-knockout (KO) rats, modeling the human Fragile X Syndrome (FXS), are of particular interest for exploring the ASD-like phenotype in preclinical studies. Gestational exposure to chlorpyrifos (CPF) has been associated with ASD diagnosis in humans and ASD-like behaviors in rodents and linked to the microbiota-gut-brain axis. In this study, we have used both Fmr1-KO and wild-type male rats (F2 generation) at postnatal days (PND) 7 and 40 obtained after F1 pregnant females were randomly exposed to 1 mg/kg/mL/day of CPF or vehicle. A nuclear magnetic resonance (NMR) metabolomics approach together with gene expression profiles of these F2 generation rats were employed to analyze different brain regions (such as prefrontal cortex, hippocampus, and cerebellum), whole large intestine (at PND7) and gut content (PND40). The statistical comparison of each matrix spectral profile unveiled tissue-specific metabolic fingerprints. Significant variations in some biomarker levels were detected among brain tissues of different genotypes, including taurine, myo-inositol, and 3-hydroxybutyric acid, and exposure to CPF induced distinct metabolic alterations, particularly in serine and myo-inositol. Additionally, this study provides a set of metabolites associated with gastrointestinal dysfunction in ASD, encompassing several amino acids, choline-derived compounds, bile acids, and sterol molecules. In terms of gene expression, genotype and gestational exposure to CPF had only minimal effects on decarboxylase 2 (gad2) and cholinergic receptor muscarinic 2 (chrm2) genes.

Keywords
AcidAnimalsAutism spectrum disorderAutism spectrum disordersBiomarkersBrainBrain-gut axisChlorpyrifosFemaleFmr1 protein, ratFragile x mental retardation proteinGastrointestinal microbiomeGlutamateMaleMetabolomicsMicrobiota-gut-brain axiMicrobiota-gut-brain axisMouse modelNuclear magnetic resonancePregnancyPrenatal exposure delayed effectsRatsSeruTaurine

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Toxicology due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 50/354, thus managing to position itself as a Q1 (Primer Cuartil), in the category Pharmacology & Pharmacy.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-04-30:

  • WoS: 1
Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-04-30:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 48.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 46 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 2.
  • The number of mentions on the social network X (formerly Twitter): 3 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.