Marcello Chieppa

@unisalento.it

Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali (DiSTeBA)
Università del Salento



              

https://researchid.co/mchieppa
93

Scopus Publications

Scopus Publications

  • The Chelating Ability of Plant Polyphenols Can Affect Iron Homeostasis and Gut Microbiota
    Aurelia Scarano, Barbara Laddomada, Federica Blando, Stefania De Santis, Giulio Verna, Marcello Chieppa, and Angelo Santino

    MDPI AG
    In the past decades, many studies have widely examined the effects of dietary polyphenols on human health. Polyphenols are well known for their antioxidant properties and for their chelating abilities, by which they can be potentially employed in cases of pathological conditions, such as iron overload. In this review, we have highlighted the chelating abilities of polyphenols, which are due to their structural specific sites, and the differences for each class of polyphenols. We have also explored how the dietary polyphenols and their iron-binding abilities can be important in inflammatory/immunomodulatory responses, with a special focus on the involvement of macrophages and dendritic cells, and how they might contribute to reshape the gut microbiota into a healthy profile. This review also provides evidence that the axes “polyphenol–iron metabolism–inflammatory responses” and “polyphenol–iron availability–gut microbiota” have not been very well explored so far, and the need for further investigation to exploit such a potential to prevent or counteract pathological conditions.

  • Increased hexosamine biosynthetic pathway flux alters cell–cell adhesion in INS-1E cells and murine islets
    Dario Domenico Lofrumento, Alessandro Miraglia, Velia La Pesa, Antonella Sonia Treglia, Marcello Chieppa, Francesco De Nuccio, Giuseppe Nicolardi, Claudia Miele, Francesco Beguinot, Corrado Garbi,et al.

    Springer Science and Business Media LLC
    Abstract Purpose In type 2 Diabetes, β-cell failure is caused by loss of cell mass, mostly by apoptosis, but also by simple dysfunction (dedifferentiation, decline of glucose-stimulated insulin secretion). Apoptosis and dysfunction are caused, at least in part, by glucotoxicity, in which increased flux of glucose in the hexosamine biosynthetic pathway plays a role. In this study, we sought to clarify whether increased hexosamine biosynthetic pathway flux affects another important aspect of β-cell physiology, that is β-cell–β-cell homotypic interactions. Methods We used INS-1E cells and murine islets. The expression and cellular distribution of E-cadherin and β-catenin was evaluated by immunofluorescence, immunohistochemistry and western blot. Cell–cell adhesion was examined by the hanging-drop aggregation assay, islet architecture by isolation and microscopic observation. Results E-cadherin expression was not changed by increased hexosamine biosynthetic pathway flux, however, there was a decrease of cell surface, and an increase in intracellular E-cadherin. Moreover, intracellular E-cadherin delocalized, at least in part, from the Golgi complex to the endoplasmic reticulum. Beta-catenin was found to parallel the E-cadherin redistribution, showing a dislocation from the plasmamembrane to the cytosol. These changes had as a phenotypic consequence a decreased ability of INS-1E to aggregate. Finally, in ex vivo experiments, glucosamine was able to alter islet structure and to decrease surface abundandance of E-cadherin and β-catenin. Conclusion Increased hexosamine biosynthetic pathway flux alters E-cadherin cellular localization both in INS-1E cells and murine islets and affects cell–cell adhesion and islet morphology. These changes are likely caused by alterations of E-cadherin function, highlighting a new potential target to counteract the consequences of glucotoxicity on β-cells.

  • Correction to: The establishment of the gut microbiota in 1‑year‑aged infants: from birth to family food (European Journal of Nutrition, (2022), 61, 5, (2517-2530), 10.1007/s00394-022-02822-1)
    Mirco Vacca, Benedetta Raspini, Francesco Maria Calabrese, Debora Porri, Rachele De Giuseppe, Marcello Chieppa, Marina Liso, Rosa Maria Cerbo, Elisa Civardi, Francesca Garofoli,et al.

    Springer Science and Business Media LLC

  • Editorial: Immune cells and inflammatory mediators in mucosal pathologies, volume II
    Maria Leite-de-Moraes, Marcello Chieppa, and Mónica Vermeulen

    Frontiers Media SA
    COPYRIGHT © 2022 Leite-de-Moraes, Chieppa and Vermeulen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. TYPE Editorial PUBLISHED 06 December 2022 DOI 10.3389/fimmu.2022.1092146

  • Deletion of TNF in Winnie-APC<sup>Min/+</sup> Mice Reveals Its Dual Role in the Onset and Progression of Colitis-Associated Colorectal Cancer
    Giulio Verna, Marina Liso, Elisabetta Cavalcanti, Raffaele Armentano, Alessandro Miraglia, Vladia Monsurrò, Marcello Chieppa, and Stefania De Santis

    MDPI AG
    Colorectal cancer (CRC) is among the best examples for depicting the relationship between inflammation and cancer. The introduction of new therapeutics targeting inflammatory mediators showed a marked decrease in the overall risk of CRC, although their chemopreventive potential is still debated. Specifically, a monoclonal antibody that blocks tumor necrosis factor (TNF), infliximab, increases CRC risk in inflammatory bowel disease patients. To address the axis between TNF and CRC development and progression, we depleted the Tnf from our previously established murine model of colitis-associated cancer (CAC), the Winnie-ApcMin/+ line. We characterized the new Winnie-APCMin/+-TNF-KO line through macroscopical and microscopical analyses. Surprisingly, the latter demonstrated that the deletion of Tnf in Winnie-ApcMin/+ mice resulted in an initial reduction in dysplastic lesion incidence in 5-week-old mice followed by a faster disease progression at 8 weeks. Histological data were confirmed by the molecular profiling obtained from both the real-time PCR analysis of the whole tissue and the RNA sequencing of the macrodissected tumoral lesions from Winnie-APCMin/+-TNF-KO distal colon at 8 weeks. Our results highlight that TNF could exert a dual role in CAC, supporting the promotion of neoplastic lesions onset in the early stage of the disease while inducing their reduction during disease progression.

  • Phenotyping of Fecal Microbiota of Winnie, a Rodent Model of Spontaneous Chronic Colitis, Reveals Specific Metabolic, Genotoxic, and Pro-inflammatory Properties
    Adelfia Talà, Flora Guerra, Silvia Caterina Resta, Matteo Calcagnile, Amilcare Barca, Salvatore Maurizio Tredici, Maria Dolores De Donno, Mirco Vacca, Marina Liso, Marcello Chieppa,et al.

    Springer Science and Business Media LLC
    Abstract Winnie, a mouse carrying a missense mutation in the MUC2 mucin gene, is a valuable model for inflammatory bowel disease (IBD) with signs and symptoms that have multiple similarities with those observed in patients with ulcerative colitis. MUC2 mucin is present in Winnie, but is not firmly compacted in a tight inner layer. Indeed, these mice develop chronic intestinal inflammation due to the primary epithelial defect with signs of mucosal damage, including thickening of muscle and mucosal layers, goblet cell loss, increased intestinal permeability, enhanced susceptibility to luminal inflammation-inducing toxins, and alteration of innervation in the distal colon. In this study, we show that the intestinal environment of the Winnie mouse, genetically determined by MUC2 mutation, selects an intestinal microbial community characterized by specific pro-inflammatory, genotoxic, and metabolic features that could imply a direct involvement in the pathogenesis of chronic intestinal inflammation. We report results obtained by using a variety of in vitro approaches for fecal microbiota functional characterization. These approaches include Caco-2 cell cultures and Caco-2/THP-1 cell co-culture models for evaluation of geno-cytotoxic and pro-inflammatory properties using a panel of 43 marker RNAs assayed by RT-qPCR, and cell-based phenotypic testing for metabolic profiling of the intestinal microbial communities by Biolog EcoPlates. While adding a further step towards understanding the etiopathogenetic mechanisms underlying IBD, the results of this study provide a reliable method for phenotyping gut microbial communities, which can complement their structural characterization by providing novel functional information.

  • LIMIT: LIfestyle and Microbiome InTeraction Early Adiposity Rebound in Children, a Study Protocol
    Rachele De Giuseppe, Federica Loperfido, Rosa Maria Cerbo, Maria Cristina Monti, Elisa Civardi, Francesca Garofoli, Micol Angelini, Beatrice Maccarini, Eduardo Sommella, Pietro Campiglia,et al.

    MDPI AG
    Childhood obesity is a strong predictor of adult obesity with health and economic consequences for individuals and society. Adiposity rebound (AR) is a rise in the Body Mass Index occurring between 3 and 7 years. Early adiposity rebound (EAR) occurs at a median age of 2 years and predisposes to a later onset of obesity. Since obesity has been associated with intestinal dysbiosis, we hypothesize that EAR could be related to early microbiome changes due to maternal/lifestyle changes and environmental exposures, which can increase the unhealthy consequences of childhood obesity. LIMIT is a prospective cohort study that aims at identifying the longitudinal interplay between infant gut microbiome, infant/maternal lifestyle, and environmental variables, in children with EAR vs. AR. Methods. The study evaluated 272 mother-infant pairs, enrolled at an Italian neonatal unit, at different time points (T0, at delivery; T1, 1 month; T2, 6 months; T3, 12 months; T4, 24 months; T5, 36 months after birth). The variables that were collected include maternal/infant anthropometric measurements, lifestyle habits, maternal environmental endocrine disruptor exposure, as well as infant AR. The LIMIT results will provide the basis for early identification of those maternal and infant modifiable factors on which to act for an effective and personalized prevention of childhood obesity.

  • The establishment of the gut microbiota in 1-year-aged infants: from birth to family food
    Mirco Vacca, Benedetta Raspini, Francesco Maria Calabrese, Debora Porri, Rachele De Giuseppe, Marcello Chieppa, Marina Liso, Rosa Maria Cerbo, Elisa Civardi, Francesca Garofoli,et al.

    Springer Science and Business Media LLC
    Abstract Purpose With the aim of characterizing the gastrointestinal (GI) microbiota and contextually determine how different prenatal, perinatal, and postnatal factors affected its composition in early childhood, infants were enrolled in a longitudinal-prospective study named “A.MA.MI.” (Alimentazione MAmma e bambino nei primi MIlle giorni; NCT04122612, October 2019). Methods Forty-five fecal samples were collected at 12 months of infants’ age, identified as the 3rd follow-up (T3). The evaluated variables were pre-gestational weight and weight gain during pregnancy, delivery mode, feeding, timing of weaning, and presence/absence of older siblings. Fecal alpha and beta-diversities were analyzed. Noteworthy, to determine the impact of the influencing factors, multivariate analyses were conducted. Results At T3, all prenatal and perinatal variables did not result to be significant whereas, among the postnatal variables, type of milk-feeding and weaning showed the greatest contribution in shaping the microbiota. Although aged 1 year, infants exclusively breastfed until 6 months were mainly colonized by Lactobacillaceae and Enterobacteriaceae. Differently, Bacteroidaceae characterized the microbiota of infants that were never breastfed in an exclusive way. Moreover, although an early introduction of solid foods determined higher values of Faith’s PD, high abundances of Ruminococcaceae and Faecalibacterium mainly associated with infants weaned after the 4th month of age. Conclusion The microbial colonization during the first year of life is likely affected by a simultaneous effect of multiple variables playing a significant role at different times. Therefore, these data contribute to add evidence concerning the complex multifactorial interaction between GI microbiota and various stimuli affecting infants during the early stages of life.


  • 1.03 - Microbiota as a Metabolic Organ Processing Dietary Polyphenols
    Aurelia Scarano, Marcello Chieppa, and Angelo Santino

    Elsevier

  • Engineering the polyphenolic biosynthetic pathway stimulates metabolic and molecular changes during fruit ripening in "Bronze" tomato
    Aurelia Scarano, Carmela Gerardi, Eduardo Sommella, Pietro Campiglia, Marcello Chieppa, Eugenio Butelli, and Angelo Santino

    Oxford University Press (OUP)
    Abstract The metabolic engineered Bronze tomato line is characterized by the constitutive over-expression of the VvStSy gene encoding a structural protein responsible for the stilbenoids biosynthesis and the fruit-specific over-expression of AmDel/Rosea1 and AtMYB12 genes encoding transcription factors that activate the polyphenol biosynthetic pathway. This tomato line is known for the increased levels of polyphenols in ripe fruits and for beneficial health promoting antioxidant and anti-inflammatory effects. In this study we analyzed the transcriptional and metabolic profiling in mature green, breaker, orange and ripe fruits compared to the normal tomato counterparts during ripening, to unravel the effect of regulatory and structural transgenes on metabolic fluxes of primary and secondary metabolisms. Our results showed that the shikimate synthase (SK) gene was up-regulated in the Bronze fruit, and the transcriptional activation is consistent with the metabolic changes observed throughout fruit ripening. These results paralleled with a reduced level of simple sugars and malate, highlighting the consumption of primary metabolites to favor secondary metabolites production and accumulation. Finally, carotenoids quantification revealed a change in the lycopene/β-carotene ratio in the Bronze fruit as a consequence of significant lower level of the first and higher levels of the latter. The high polyphenols and β-carotene content displayed by the Bronze fruit at the later stages of fruit ripening renders this line an interesting model to study the additive or synergic effects of these phyto-chemicals in the prevention of human pathologies.

  • Interleukin 1β Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor–Independent Ulcerative Colitis
    Marina Liso, Giulio Verna, Elisabetta Cavalcanti, Stefania De Santis, Raffaele Armentano, Angela Tafaro, Antonio Lippolis, Pietro Campiglia, Antonio Gasbarrini, Mauro Mastronardi,et al.

    Elsevier BV

  • Nutritional Regimes Enriched with Antioxidants as an Efficient Adjuvant for IBD Patients under Infliximab Administration, a Pilot Study
    Marina Liso, Annamaria Sila, Giulio Verna, Aurelia Scarano, Rossella Donghia, Fabio Castellana, Elisabetta Cavalcanti, Pasqua Letizia Pesole, Eduardo Maria Sommella, Antonio Lippolis,et al.

    MDPI AG
    Antioxidants are privileged candidates for the development of adjuvants able to improve the efficiency of pharmacological therapies, particularly for chronic inflammatory syndromes. During the last 20 years, anti-TNFα (tumor necrosis factor alpha) monoclonal antibodies infusion has been the biological therapy most frequently administered but there is still large space for improvement in disease remission rates and maintenance. In this context, nutritional bioactive compounds contained in dietary patterns or included as supplements, may act as adjuvants for the induction and maintenance of IBD (inflammatory bowel diseases) remission. To verify this possibility, a single-center preliminary study (SI-CURA, Soluzioni Innovative per la gestione del paziente e il follow up terapeutico della Colite UlceRosA) was designed and carried out to evaluate whether a daily administration of purple corn supplement could improve the response to Infliximab (IFX) infusion of IBD patients with both Crohn’s disease (CD) and ulcerative colitis (UC). A cohort of 47 patients was enrolled in the study. Biological samples were collected before the first and the third IFX infusion. All patients received nutritional guidelines, 27 of them received commercial red fruit tea with low anthocyanins content, while 20 received a purple corn supplement with a high anthocyanin content. Results show that the administration of an antioxidant-enriched purple corn supplement could improve IFX-mediated disease remission in terms of circulating inflammatory markers. Comparison between CD and UC patients revealed that, at this anthocyanin dosage, the purple corn extract administration improved the IFX response in CD but not in UC patients. Our results may pave the way for a new metacentric study of CD patients, recruiting a wider cohort and followed-up over a longer observational time.

  • Hop-derived fraction rich in beta acids and prenylflavonoids regulates the inflammatory response in dendritic cells differently from quercetin: Unveiling metabolic changes by mass spectrometry-based metabolomics
    Eduardo Sommella, Giulio Verna, Marina Liso, Emanuela Salviati, Tiziana Esposito, Daniela Carbone, Camilla Pecoraro, Marcello Chieppa, and Pietro Campiglia

    Royal Society of Chemistry (RSC)
    Metabolomics highlights that Hop fraction rich in bitter acids and prenylflavonoids modulates dendritic cells inflammatory status.

  • Quercetin administration suppresses the cytokine storm in myeloid and plasmacytoid dendritic cells
    Giulio Verna, Marina Liso, Elisabetta Cavalcanti, Giusy Bianco, Veronica Di Sarno, Angelo Santino, Pietro Campiglia, and Marcello Chieppa

    MDPI AG
    Dendritic cells (DCs) can be divided by lineage into myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs). They both are present in mucosal tissues and regulate the immune response by secreting chemokines and cytokines. Inflammatory bowel diseases (IBDs) are characterized by a leaky intestinal barrier and the consequent translocation of bacterial lipopolysaccharide (LPS) to the basolateral side. This results in DCs activation, but the response of pDCs is still poorly characterized. In the present study, we compared mDCs and pDCs responses to LPS administration. We present a broad panel of DCs secreted factors, including cytokines, chemokines, and growth factors. Our recent studies demonstrated the anti-inflammatory effects of quercetin administration, but to date, there is no evidence about quercetin’s effects on pDCs. The results of the present study demonstrate that pDCs can respond to LPS and that quercetin exposure modulates soluble factors release through the same molecular pathway used by mDCs (Slpi, Hmox1, and AP-1).

  • Neglected and underutilized plant species (Nus) from the apulia region worthy of being rescued and re-included in daily diet
    Aurelia Scarano, Teodoro Semeraro, Marcello Chieppa, and Angelo Santino

    MDPI AG
    Neglected and underutilized species (NUS) are cultivated, semi-domesticated, or wild plant species, not included in the group of the major staple crops, since, in most cases, they do not meet the global market requirements. As they often represent resilient species and valuable sources of vitamins, micronutrients, and other phytochemicals, a wider use of NUS would enhance sustainability of agro-systems and a choice of nutritious foods with a strategic role for addressing the nutritional security challenge across Europe. In this review, we focused on some examples of NUS from the Apulia Region (Southern Italy), either cultivated or spontaneously growing species, showing interesting adaptative, nutritional, and economical potential that can be exploited and properly enhanced in future programs.

  • Extra virgin olive oil extracts modulate the inflammatory ability of murine dendritic cells based on their polyphenols pattern: Correlation between chemical composition and biological function
    Stefania De Santis, Marina Liso, Giulio Verna, Francesca Curci, Gualtiero Milani, Maria Felicia Faienza, Carlo Franchini, Antonio Moschetta, Marcello Chieppa, Maria Lisa Clodoveo,et al.

    MDPI AG
    Extra virgin olive oil (EVOO) represents one of the most important health-promoting foods whose antioxidant and anti-inflammatory activities are mainly associated to its polyphenols content. To date, studies exploring the effect of EVOO polyphenols on dendritic cells (DCs), acting as a crosstalk between the innate and the adaptive immune response, are scanty. Therefore, we studied the ability of three EVOO extracts (cv. Coratina, Cima di Mola/Coratina, and Casaliva), characterized by different polyphenols amount, to regulate DCs maturation in resting conditions or after an inflammatory stimulus. Cima di Mola/Coratina and Casaliva extracts were demonstrated to be the most effective in modulating DCs toward an anti-inflammatory profile by reduction of TNF and IL-6 secretion and CD86 expression, along with a down-modulation of Il-1β and iNOS expression. From factorial analysis results, 9 polyphenols were tentatively established to play a synergistic role in modulating DCs inflammatory ability, thus reducing the risk of chronic inflammation.

  • Dietary Habits and Nutrient Intakes Are Associated to Age-Related Central Auditory Processing Disorder in a Cohort From Southern Italy
    Luisa Lampignano, Nicola Quaranta, Ilaria Bortone, Sarah Tirelli, Roberta Zupo, Fabio Castellana, Rossella Donghia, Vito Guerra, Chiara Griseta, Pasqua Letizia Pesole,et al.

    Frontiers Media SA
    ObjectivesCentral auditory processing disorder (CAPD) commonly occurs in older age. However, few studies of a possible link between age-related CAPD and diet in an older population have been conducted. The objective of the present study was to investigate the relationship between eating habits and age-related CAPD in a population &amp;gt;65 years, using cross-sectional and retrospective data obtained in the same population-based study about 12 years ago.MethodsWe selected 734 participants (403 men) from a large population-based study. For age-related CAPD assessment, we used the Synthetic Sentence Identification with Ipsilateral Competitive Message test. Dietary habits were assessed by a Food Frequency Questionnaire. Associations between age-related CAPD and food groups/macro-and micronutrients were explored using adjusted logistic regression models.ResultsAge-related CAPD subjects consumed more dairy (111 vs. 98 g/d), olives and vegetable oil (63 vs. 52 g/d) and spirits (2 vs.1 g/d), and less fruits (536 vs. 651 g/d) in the cross-sectional analysis. Age-related CAPD subjects had a lower intake of potassium, vitamin C, and a higher fat intake. Further analyses identified dietary fiber as being inversely related to age-related CAPD.DiscussionThe present study provided evidence that the dietary hypotheses proposed for explaining the development of cognitive disorders in older age might also hold for age-related CAPD. Further data from other large and prospective population-based studies are needed for confirming these findings.

  • Early Life Microbiota Colonization at Six Months of Age: A Transitional Time Point
    Benedetta Raspini, Mirco Vacca, Debora Porri, Rachele De Giuseppe, Francesco Maria Calabrese, Marcello Chieppa, Marina Liso, Rosa Maria Cerbo, Elisa Civardi, Francesca Garofoli,et al.

    Frontiers Media SA
    BackgroundEarly life gut microbiota is involved in several biological processes, particularly metabolism, immunity, and cognitive neurodevelopment. Perturbation in the infant’s gut microbiota increases the risk for diseases in early and later life, highlighting the importance of understanding the connections between perinatal factors with early life microbial composition. The present research paper is aimed at exploring the prenatal and postnatal factors influencing the infant gut microbiota composition at six months of age.MethodsGut microbiota of infants enrolled in the longitudinal, prospective, observational study “A.MA.MI” (Alimentazione MAmma e bambino nei primi MIlle giorni) was analyzed. We collected and analyzed 61 fecal samples at baseline (meconium, T0); at six months of age (T2), we collected and analyzed 53 fecal samples. Samples were grouped based on maternal and gestational weight factors, type of delivery, type of feeding, time of weaning, and presence/absence of older siblings. Alpha and beta diversities were evaluated to describe microbiota composition. Multivariate analyses were performed to understand the impact of the aforementioned factors on the infant’s microbiota composition at six months of age.ResultsDifferent clustering hypotheses have been tested to evaluate the impact of known metadata factors on the infant microbiota. Neither maternal body mass index nor gestational weight gain was able to determine significant differences in infant microbiota composition six months of age. Concerning the type of feeding, we observed a low alpha diversity in exclusive breastfed infants; conversely, non-exclusively breastfed infants reported an overgrowth of Ruminococcaceae and Flavonifractor. Furthermore, we did not find any statistically significant difference resulting from an early introduction of solid foods (before 4 months of age). Lastly, our sample showed a higher abundance of clostridial patterns in firstborn babies when compared to infants with older siblings in the family.ConclusionOur findings showed that, at this stage of life, there is not a single factor able to affect in a distinct way the infants’ gut microbiota development. Rather, there seems to be a complex multifactorial interaction between maternal and neonatal factors determining a unique microbial niche in the gastrointestinal tract.

  • Iron-enriched nutritional supplements for the 2030 pharmacy shelves
    Giulio Verna, Annamaria Sila, Marina Liso, Mauro Mastronardi, Marcello Chieppa, Hellas Cena, and Pietro Campiglia

    MDPI AG
    Iron deficiency (ID) affects people of all ages in many countries. Due to intestinal blood loss and reduced iron absorption, ID is a threat to IBD patients, women, and children the most. Current therapies can efficiently recover normal serum transferrin saturation and hemoglobin concentration but may cause several side effects, including intestinal inflammation. ID patients may benefit from innovative nutritional supplements that may satisfy iron needs without side effects. There is a growing interest in new iron-rich superfoods, like algae and mushrooms, which combine antioxidant and anti-inflammatory properties with iron richness.

  • Dysbiosis triggers ACF development in genetically predisposed subjects
    Stefania De Santis, Marina Liso, Mirco Vacca, Giulio Verna, Elisabetta Cavalcanti, Sergio Coletta, Francesco Maria Calabrese, Rajaraman Eri, Antonio Lippolis, Raffaele Armentano,et al.

    MDPI AG
    Background: Colorectal cancer (CRC) is the third most common cancer worldwide, characterized by a multifactorial etiology including genetics, lifestyle, and environmental factors including microbiota composition. To address the role of microbial modulation in CRC, we used our recently established mouse model (the Winnie-APCMin/+) combining inflammation and genetics. Methods: Gut microbiota profiling was performed on 8-week-old Winnie-APCMin/+ mice and their littermates by 16S rDNA gene amplicon sequencing. Moreover, to study the impact of dysbiosis induced by the mother’s genetics in ACF development, the large intestines of APCMin/+ mice born from wild type mice were investigated by histological analysis at 8 weeks. Results: ACF development in 8-week-old Winnie-APCMin/+ mice was triggered by dysbiosis. Specifically, the onset of ACF in genetically predisposed mice may result from dysbiotic signatures in the gastrointestinal tract of the breeders. Additionally, fecal transplant from Winnie donors to APCMin/+ hosts leads to an increased rate of ACF development. Conclusions: The characterization of microbiota profiling supporting CRC development in genetically predisposed mice could help to design therapeutic strategies to prevent dysbiosis. The application of these strategies in mothers during pregnancy and lactation could also reduce the CRC risk in the offspring.

  • Polyphenol enriched diet administration during pregnancy and lactation prevents dysbiosis in ulcerative colitis predisposed littermates
    Stefania De Santis, Aurelia Scarano, Marina Liso, Francesco Maria Calabrese, Giulio Verna, Elisabetta Cavalcanti, Annamaria Sila, Antonio Lippolis, Maria De Angelis, Angelo Santino,et al.

    Frontiers Media SA
    Neonatal colonization of the gastrointestinal tract depends on mother microbiome, thus mother microbiota dysbiosis is transmitted to the offspring during the delivery and shaped by breastmilk characteristics. Here we used a murine model of UC predisposition (Winnie-/-) to evaluate the effects of maternal diet during pregnancy and lactation. Using heterozygous breeders, we obtained both Winnie-/- and C57BL/6 littermates from the same mother and compared their microbiota at weaning and adult age, using a diet enriched with 1% tomato fruit of a line – named Bronze – highly enriched in bioactive polyphenols, or Control tomato. Females received enriched diets two weeks before the beginning of the breeding and never stopped for the following six months. No significant effect was observed in regard to the percentage of Winnie-/- offspring, as with both diets the percentage was about 25% as expected. Winnie littermates from breeders fed with the Bronze-enriched diet showed reduced dysbiosis at 4 weeks of age if compared with Winnie under the Control tomato diet. This effect was then reduced when mice reached adult age. Conversely, the microbiota of C57BL/6 does not change significantly, indicating that fortified mothers-diet significantly contribute to preventing dysbiosis in genetically predisposed offspring, but has mild effects on healthy littermates and adult mice. An overall tendency towards reduced inflammation was underlined by the colon weight and the percentage of Foxp3+ cells reduction in Winnie mice fed with Bronze diet. Control diet did not show similar tendency.

  • Plant polyphenols-biofortified foods as a novel tool for the prevention of human gut diseases
    Aurelia Scarano, Marcello Chieppa, and Angelo Santino

    MDPI AG
    Plant food biofortification is recently receiving remarkable attention, as it aims to increase the intake of minerals, vitamins, or antioxidants, crucial for their contribution to the general human health status and disease prevention. In this context, the study of the plant’s secondary metabolites, such as polyphenols, plays a pivotal role for the development of a new generation of plant crops, compensating, at least in part, the low nutritional quality of Western diets with a higher quality of dietary sources. Due to the prevalent immunomodulatory activity at the intestinal level, polyphenols represent a nutritionally relevant class of plant secondary metabolites. In this review, we focus on the antioxidant and anti-inflammatory properties of different classes of polyphenols with a specific attention to their potential in the prevention of intestinal pathological processes. We also discuss the latest biotechnology strategies and new advances of genomic techniques as a helpful tool for polyphenols biofortification and the development of novel, healthy dietary alternatives that can contribute to the prevention of inflammatory bowel diseases.

  • miR-369-3p modulates inducible nitric oxide synthase and is involved in regulation of chronic inflammatory response
    Viviana Scalavino, Marina Liso, Elisabetta Cavalcanti, Isabella Gigante, Antonio Lippolis, Mauro Mastronardi, Marcello Chieppa, and Grazia Serino

    Springer Science and Business Media LLC
    AbstractDendritic cells are the most important antigen-presenting cells that link the innate and acquired immune system. In our previous study, we identified that the upregulation of miR-369-3p suppresses the LPS-induced inflammatory response, reducing C/EBP-β, TNFα and IL-6 production. With the aim of gaining further insight into the biological function of miR-369-3p during acute inflammatory response, in the present study we identified novel gene targets of miR-369-3p and demonstrated the suppressive ability of these genes on the inflammatory dendritic cells. Bioinformatic analyses revealed that iNOS is a potential target of miR-369-3p. We demonstrated that the ectopic induction of miR-369-3p markedly reduced iNOS mRNA and protein as well as NO production. Moreover, we found that the upregulation of miR-369-3p decreased the release of TNFα, IL-6, IL-12, IL-1α, IL-1β in response to LPS, and increased the production of anti-inflammatory cytokines such as IL-10 and IL-1RA. In addition, LPS-induced nuclear translocation of NF-kB was inhibited by miR-369-3p. Levels of miR-369-3p were decreased in human inflamed regions of human intestine obtained from IBD patients. Our results provide novel additional information on miR-369-3p as a potential core of the signaling regulating the inflammatory response. These findings suggest that miR-369-3p should be considered as a potential target for the future development of new molecular therapeutic approaches.

  • Diet influences the functions of the human intestinal microbiome
    Maria De Angelis, Ilario Ferrocino, Francesco Maria Calabrese, Francesca De Filippis, Noemi Cavallo, Sonya Siragusa, Simone Rampelli, Raffaella Di Cagno, Kalliopi Rantsiou, Lucia Vannini,et al.

    Springer Science and Business Media LLC
    AbstractGut microbes programme their metabolism to suit intestinal conditions and convert dietary components into a panel of small molecules that ultimately affect host physiology. To unveil what is behind the effects of key dietary components on microbial functions and the way they modulate host–microbe interaction, we used for the first time a multi-omic approach that goes behind the mere gut phylogenetic composition and provides an overall picture of the functional repertoire in 27 fecal samples from omnivorous, vegan and vegetarian volunteers. Based on our data, vegan and vegetarian diets were associated to the highest abundance of microbial genes/proteins responsible for cell motility, carbohydrate- and protein-hydrolyzing enzymes, transport systems and the synthesis of essential amino acids and vitamins. A positive correlation was observed when intake of fiber and the relative fecal abundance of flagellin were compared. Microbial cells and flagellin extracted from fecal samples of 61 healthy donors modulated the viability of the human (HT29) colon carcinoma cells and the host response through the stimulation of the expression of Toll-like receptor 5, lectin RegIIIα and three interleukins (IL-8, IL-22 and IL-23). Our findings concretize a further and relevant milestone on how the diet may prevent/mitigate disease risk.