Publications by authors named "Silvia Falcinelli"

11 Publications

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The probiotic Lactobacillus rhamnosus mimics the dark-driven regulation of appetite markers and melatonin receptors' expression in zebrafish (Danio rerio) larvae: Understanding the role of the gut microbiome.

Comp Biochem Physiol B Biochem Mol Biol 2021 Jun 11;256:110634. Epub 2021 Jun 11.

Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona 08028, Spain. Electronic address:

The use of probiotics has been recently considered a novel therapeutic strategy to prevent pathologies such as obesity; however, the specific mechanisms of action by which probiotics exert their beneficial effects on metabolic health remain unclear. The aim of the present study was to investigate the short-term effects of a probiotic Lactobacillus rhamnosus supplementation (PROB) on appetite regulation, growth-related markers, and microbiota diversity in zebrafish (Danio rerio) larvae, compared to a group subjected to a constant darkness photoperiod (DARK), as well as to evaluate the effects of both treatments on melatonin receptors' expression. After a 24 h treatment, both PROB and DARK conditions caused a significant increase in leptin a expression. Moreover, mRNA abundances of leptin b and proopiomelanocortin a were elevated in the PROB group, and DARK showed a similar tendency, supporting a negative regulation of appetite markers by the treatments. Moreover, both PROB and DARK also enhanced the abundances of melatonin receptors transcript (melatonin receptor 1 ba and bb) and protein (melatonin receptor 1) suggesting a potential involvement of melatonin in mediating these effects. Nevertheless, treatments did not exhibit a significant effect on the expression of most of the growth hormone/insulin-like growth factor axis genes evaluated. Finally, only the DARK condition significantly modulated gut microbiota diversity at such short time, altogether highlighting the rapid effects of this probiotic on modulating appetite regulatory and melatonin receptors' expression, without a concomitant variation of gut microbiota.
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http://dx.doi.org/10.1016/j.cbpb.2021.110634DOI Listing
June 2021

Photoperiod Manipulation Affects Transcriptional Profile of Genes Related to Lipid Metabolism and Apoptosis in Zebrafish (Danio rerio) Larvae: Potential Roles of Gut Microbiota.

Microb Ecol 2020 May 9;79(4):933-946. Epub 2019 Dec 9.

Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, Ancona, Italy.

Gut microbiota plays a fundamental role in maintaining host's health by controlling a wide range of physiological processes. Administration of probiotics and manipulation of photoperiod have been suggested as modulators of microbial composition and are currently undergoing an extensive research in aquaculture as a way to improve health and quality of harvested fish. However, our understanding regarding their effects on physiological processes is still limited. In the present study we investigated whether manipulation of photoperiod and/or probiotic administration was able to alter microbial composition in zebrafish larvae at hatching stage. Our findings show that probiotic does not elicit effects while photoperiod manipulation has a significant impact on microbiota composition. Moreover, we successfully predicted lipid biosynthesis and apoptosis to be modulated by microbial communities undergoing continuous darkness. Interestingly, expression levels of caspase 3 gene (casp3) and lipid-related genes (hnf4a, npc1l1, pparγ, srebf1, agpat4 and fitm2) were found to be significantly overexpressed in dark-exposed larvae, suggesting an increase in the occurrence of apoptotic processes and a lipid metabolism impairment, respectively (p < 0.05). Our results provide the evidence that microbial communities in zebrafish at early life stages are not modulated by a short administration of probiotics and highlight the significant effect that dark photoperiod elicits on zebrafish microbiota and potentially on health.
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http://dx.doi.org/10.1007/s00248-019-01468-7DOI Listing
May 2020

Transcriptomic analysis of short-term 17α-ethynylestradiol exposure in two Californian sentinel fish species sardine (Sardinops sagax) and mackerel (Scomber japonicus).

Environ Pollut 2019 Jan 20;244:926-937. Epub 2018 Oct 20.

Department of Medicine, Nephrology, Medical University of South Carolina, Charleston, SC, USA; Biomedical Informatics Research Center, San Diego State University, San Diego, CA, USA; MUSC Bioinformatics, Center for Genomics Medicine, Medical University of South Carolina, Charleston, SC, USA; Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA; Laboratory for Marine Systems Biology, Hollings Marine Laboratory, Charleston, SC, USA; School of Biological Sciences & Institute for Global Food Security, Queens University Belfast, Stranmillis Road, Belfast BT9 5AG, UK. Electronic address:

Endocrine disrupting chemicals (EDCs) are substances which disrupt normal functioning of the endocrine system by interfering with hormone regulated physiological pathways. Aquatic environments provide the ultimate reservoir for many EDCs as they enter rivers and the ocean via effluent discharges and accumulate in sediments. One EDC widely dispersed in municipal wastewater effluent discharges is 17α-ethynylestradiol (EE2), which is one of the most widely prescribed medicines. EE2 is a bio-active estrogen employed in the majority of oral contraceptive pill formulations. As evidence of the health risks posed by EDCs mount, there is an urgent need to improve diagnostic tools for monitoring the effects of pollutants. As the cost of high throughput sequencing (HTS) diminishes, transcriptional profiling of an organism in response to EDC perturbation presents a cost-effective way of screening a wide range of endocrine responses. Coastal pelagic filter feeding fish species analyzed using HTS provide an excellent tool for EDC risk assessment in the marine environment. Unfortunately, there are limited genome sequence data and annotation for many of these species including Pacific sardine (Sardinops sagax) and chub mackerel (Scomber japonicus), which limits the utility of molecular tools such as HTS to interrogate the effects of endocrine disruption. In this study, we carried out RNA sequencing (RNAseq) of liver RNA harvested from wild sardine and mackerel exposed for 5 h under laboratory conditions to a concentration of 12.5 pM EE2 in the tank water. We developed an analytical framework for transcriptomic analyses of species with limited genomic information. EE2 exposure altered expression patterns of key genes involved in important metabolic and physiological processes. The systems approach presented here provides a powerful tool for obtaining a comprehensive picture of endocrine disruption in aquatic organisms.
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http://dx.doi.org/10.1016/j.envpol.2018.10.058DOI Listing
January 2019

Influence of Probiotics Administration on Gut Microbiota Core: A Review on the Effects on Appetite Control, Glucose, and Lipid Metabolism.

J Clin Gastroenterol 2018 Nov/Dec;52 Suppl 1, Proceedings from the 9th Probiotics, Prebiotics and New Foods, Nutraceuticals and Botanicals for Nutrition & Human and Microbiota Health Meeting, held in Rome, Italy from September 10 to 12, 2017:S50-S56

Department of Life and Environmental Sciences (DiSVA), Marche Polytechnic University, Ancona.

An increasing number of studies has shown that dietary probiotics exert beneficial health effects in both humans and animals. It is well established that gut microbiota play a pivotal role in regulating host metabolism, and a growing number of studies has elucidated that probiotics positively interfere with gut microbiota. Accumulating evidence shows that probiotics, through their metabolic activity, produce metabolites that in turn contribute to positively affect host physiology. For these reasons, probiotics have shown significant potential as a therapeutic tool for a diversity of diseases, but the mechanisms through which probiotics act has not been fully elucidated yet. The goal of this review was to provide evidence on the effects of probiotics on gut microbiota changes associated with host metabolic variations, specifically focusing on feed intake and lipid and glucose metabolism. In addition, we review probiotic interaction with the gut microbiota. The information collected here will give further insight into the effects of probiotics on the gut microbiota and their action on metabolite release, energy metabolism, and appetite. This information will help to improve knowledge to find better probiotic therapeutic strategies for obesity and eating disorders.
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http://dx.doi.org/10.1097/MCG.0000000000001064DOI Listing
October 2019

The Plasticizer Bisphenol A Perturbs the Hepatic Epigenome: A Systems Level Analysis of the miRNome.

Genes (Basel) 2017 Oct 13;8(10). Epub 2017 Oct 13.

Division of Nephrology, Department of Medicine, Medical University of South Carolina (MUSC),Charleston, SC 29425, USA.

Ubiquitous exposure to bisphenol A (BPA), an endocrine disruptor (ED), has raised concerns for both human and ecosystem health. Epigenetic factors, including microRNAs (miRNAs), are key regulators of gene expression during cancer. The effect of BPA exposure on the zebrafish epigenome remains poorly characterized. Zebrafish represents an excellent model to study cancer as the organism develops a disease that resembles human cancer. Using zebrafish as a systems toxicology model, we hypothesized that chronic BPA-exposure impacts the miRNome in adult zebrafish and establishes an epigenome more susceptible to cancer development. After a 3 week exposure to 100 nM BPA, RNA from the liver was extracted to perform high throughput mRNA and miRNA sequencing. Differential expression (DE) analyses comparing BPA-exposed to control specimens were performed using established bioinformatics pipelines. In the BPA-exposed liver, 6188 mRNAs and 15 miRNAs were differently expressed (q ≤ 0.1). By analyzing human orthologs of the DE zebrafish genes, signatures associated with non-alcoholic fatty liver disease (NAFLD), oxidative phosphorylation, mitochondrial dysfunction and cell cycle were uncovered. Chronic exposure to BPA has a significant impact on the liver miRNome and transcriptome in adult zebrafish with the potential to cause adverse health outcomes including cancer.
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http://dx.doi.org/10.3390/genes8100269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5664119PMC
October 2017

Dietary lipid content reorganizes gut microbiota and probiotic L. rhamnosus attenuates obesity and enhances catabolic hormonal milieu in zebrafish.

Sci Rep 2017 07 17;7(1):5512. Epub 2017 Jul 17.

Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, Ancona, Italy.

In the present study, we explored whether dietary lipid content influences the gut microbiome in adult zebrafish. Diets containing three different lipid levels (high [HFD], medium [MFD], and low [LFD]) were administered with or without the supplementation of Lactobacillus rhamnosus (P) to zebrafish in order to explore how the dietary lipid content may influence the gut microbiome. Dietary lipid content shifted the gut microbiome structure. The addition of L. rhamnosus in the diets, induced transcriptional reduction of orexigenic genes, upregulation of anorexigenic genes, and transcriptional decrease of genes involved in cholesterol and triglyceride (TAG) metabolism, concomitantly with lower content of cholesterol and TAG. Probiotic feeding also decreased nesfatin-1 peptide in HFD-P and attenuated weight gain in HFD-P and MFD-P fed zebrafish, but not in LFD-P group. Intestinal ultrastructure was not affected by dietary fat level or probiotic inclusion. In conclusion, these findings underline the role of fat content in the diet in altering gut microbiota community by shifting phylotype composition and highlight the potential of probiotics to attenuate high-fat diet-related metabolic disorder.
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http://dx.doi.org/10.1038/s41598-017-05147-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514052PMC
July 2017

Acute stress enhances the expression of neuroprotection- and neurogenesis-associated genes in the hippocampus of a mouse restraint model.

Oncotarget 2016 Feb;7(8):8455-65

Department of Medicine, School of Medicine, University of California, La Jolla, California, USA.

Stress arises from an external demand placed on an organism that triggers physiological, cognitive and behavioural responses in order to cope with that request. It is thus an adaptive response useful for the survival of an organism. The objective of this study was to identify and characterize global changes in gene expression in the hippocampus in response to acute stress stimuli, by employing a mouse model of short-term restraint stress. In our experimental design mice were subjected to a one time exposure of restraint stress and the regulation of gene expression in the hippocampus was examined 3, 12 and 24 hours thereafter. Microarray analysis revealed that mice which had undergone acute restraint stress differed from non-stressed controls in global hippocampal transcriptional responses. An up-regulation of transcripts contributing directly or indirectly to neurogenesis and neuronal protection including, Ttr, Rab6, Gh, Prl, Ndufb9 and Ndufa6, was observed. Systems level analyses revealed a significant enrichment for neurogenesis, neuron morphogenesis- and cognitive functions-related biological process terms and pathways. This work further supports the hypothesis that acute stress mediates a positive action on the hippocampus favouring the formation and the preservation of neurons, which will be discussed in the context of current data from the literature.
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http://dx.doi.org/10.18632/oncotarget.7225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890979PMC
February 2016

Probiotic treatment reduces appetite and glucose level in the zebrafish model.

Sci Rep 2016 Jan 5;6:18061. Epub 2016 Jan 5.

Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, Ancona, Italy.

The gut microbiota regulates metabolic pathways that modulate the physiological state of hunger or satiety. Nutrients in the gut stimulate the release of several appetite modulators acting at central and peripheral levels to mediate appetite and glucose metabolism. After an eight-day exposure of zebrafish larvae to probiotic Lactobacillus rhamnosus, high-throughput sequence analysis evidenced the ability of the probiotic to modulate the microbial composition of the gastrointestinal tract. These changes were associated with a down-regulation and up-regulation of larval orexigenic and anorexigenic genes, respectively, an up-regulation of genes related to glucose level reduction and concomitantly reduced appetite and body glucose level. BODIPY-FL-pentanoic-acid staining revealed higher short chain fatty acids levels in the intestine of treated larvae. These results underline the capability of the probiotic to modulate the gut microbiota community and provides insight into how the probiotic interacts to regulate a novel gene network involved in glucose metabolism and appetite control, suggesting a possible role for L. rhamnosus in the treatment of impaired glucose tolerance and food intake disorders by gut microbiota manipulation.
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http://dx.doi.org/10.1038/srep18061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700460PMC
January 2016

Biomarkers of hippocampal gene expression in a mouse restraint chronic stress model.

Pharmacogenomics 2015 ;16(5):471-82

School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri 9, Camerino, Italy.

Objective: Acute stress provides many beneficial effects whereas chronic stress contributes to a variety of human health issues including anxiety, depression, gastrointestinal problems, cardiac disease, sleep disorders and obesity. The goal of this work was to identify, using a rodent model, hippocampal gene signatures associated with prolonged chronic stress representing candidate biomarkers and therapeutic targets for early diagnosis and pharmacological intervention for stress induced disease.

Materials & Methods: Mice underwent 'restraint stress' over 7 consecutive days and hippocampal gene-expression changes were analyzed at 3, 12 and 24 h following the final restraint treatment.

Results: Data indicated that mice exposed to chronic restraint stress exhibit a differential gene-expression profile compared with non-stressed controls. The greatest differences were observed 12 and 24 h following the final stress test.

Conclusion: Our study indicated that Gpr88, Ttr, Gh and Tac1 mRNAs were modulated in mice exposed to chronic restraint stress. These transcripts represent a panel of biomarkers and druggable targets for further analysis in the context of chronic stress associated disease in humans.
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http://dx.doi.org/10.2217/pgs.15.3DOI Listing
January 2016

Lactobacillus rhamnosus lowers zebrafish lipid content by changing gut microbiota and host transcription of genes involved in lipid metabolism.

Sci Rep 2015 Mar 30;5:9336. Epub 2015 Mar 30.

Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, Ancona, Italy.

The microbiome plays an important role in lipid metabolism but how the introduction of probiotic communities affects host lipid metabolism is poorly understood. Using a multidisciplinary approach we addressed this knowledge gap using the zebrafish model by coupling high-throughput sequencing with biochemical, molecular and morphological analysis to evaluate the changes in the intestine. Analysis of bacterial 16S libraries revealed that Lactobacillus rhamnosus was able to modulate the gut microbiome of zebrafish larvae, elevating the abundance of Firmicutes sequences and reducing the abundance of Actinobacteria. The gut microbiome changes modulated host lipid processing by inducing transcriptional down-regulation of genes involved in cholesterol and triglycerides metabolism (fit2, agpat4, dgat2, mgll, hnf4α, scap, and cck) concomitantly decreasing total body cholesterol and triglyceride content and increasing fatty acid levels. L. rhamnosus treatment also increased microvilli and enterocyte lengths and decreased lipid droplet size in the intestinal epithelium. These changes resulted in elevated zebrafish larval growth. This integrated system investigation demonstrates probiotic modulation of the gut microbiome, highlights a novel gene network involved in lipid metabolism, provides an insight into how the microbiome regulates molecules involved in lipid metabolism, and reveals a new potential role for L. rhamnosus in the treatment of lipid disorders.
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http://dx.doi.org/10.1038/srep09336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4378510PMC
March 2015

Probiotic supplementation promotes calcification in Danio rerio larvae: a molecular study.

PLoS One 2013 17;8(12):e83155. Epub 2013 Dec 17.

Dipartimento di Scienze della Vita e dell'Ambiente, Università Politecnica delle Marche, Ancona, Italia ; Istituto Nazionale Biostrutture e Biosistemi, Roma, Italia.

A growing number of studies have been showing that dietary probiotics can exert beneficial health effects in both humans and animals. We previously demonstrated that dietary supplementation with Lactobacillus rhamnosus - a component of the human gut microflora - enhances reproduction, larval development, and the biomineralization process in Danio rerio (zebrafish). The aim of this study was to identify the pathways affected by L. rhamnosus during zebrafish larval development. Our morphological and histochemical findings show that L. rhamnosus accelerates bone deposition through stimulation of the expression of key genes involved in ossification, e.g. runt-related transcription factor 2 (runx2), Sp7 transcription factor (sp7), matrix Gla protein (mgp), and bone gamma-carboxyglutamate (gla) protein (bglap) as well as through inhibition of sclerostin (sost), a bone formation inhibitor. Western blot analysis of mitogen-activated protein kinase 1 and 3-(Mapk1 and Mapk3), which are involved in osteoblast and osteocyte differentiation, documented an increase in Mapk1 16 days post fertilization (dpf) and of Mapk3 23 dpf in individuals receiving L. rhamnosus supplementation. Interestingly, a reduction of sost detected in the same individuals suggests that the probiotic may help treat bone disorders.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0083155PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3866187PMC
October 2014
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