Translational Medical Science Research Articles

Increased dietary intake of ultraprocessed foods and mitochondrial metabolism alterations in pediatric obesity

The increased intake of ultraprocessed foods (UPFs) in the pediatric age paralleled with the risen prevalence of childhood obesity. The Ultraprocessed Foods in Obesity (UFO) Project aimed at investigating the potential mechanisms for the effects of UPFs in facilitating pediatric obesity, focusing on the direct role of advanced glycation end-products (AGEs) on mitochondrial function, the key regulator of obesity pathophysiology. We comparatively investigated the daily dietary intake of UPFs, energy, nutrients, dietary AGEs [Nε -(carboxymethyl)lysine (CML), Nε -(1-carboxyethyl)lysine (CEL), and Nδ -(5-hydro-5- methyl-4-imidazolon-2-yl)-ornithine (MG-H1)] in 53 obese patients and in 100 healthy controls visiting the Tertiary Center for Pediatric Nutrition of the Department of Translational Medical Science at the University of Naples “Federico II”. AGEs skin accumulation and mitochondrial function in peripheral blood mononuclear cells (PBMCs) were also assessed. A higher intake of UPFs and AGEs, energy, protein, fat, and saturated fatty acids was observed in obese patients. Obese children presented significantly higher skin AGEs accumulation and alterations in mitochondrial metabolism. PBMCs from healthy controls exposed to AGEs showed the same mitochondrial alterations observed in patients. These findings support the UPFs role in pediatric obesity, and the need for dietary strategies limiting UPFs exposure for obesity prevention and treatment.

Mitochondrial Dysfunction as a Signaling Target for Therapeutic Intervention in Major Neurodegenerative Disease.

Neurodegenerative diseases (NDD) are incurable and the most prevalent cognitive and motor disorders of elderly. Mitochondria are essential for a wide range of cellular processes playing a pivotal role in a number of cellular functions like metabolism, intracellular signaling, apoptosis, and immunity. A plethora of evidence indicates the central role of mitochondrial functions in pathogenesis of many aging related NDD. Considering how mitochondria function in neurodegenerative diseases, oxidative stress, and mutations in mtDNA both contribute to aging. Many substantial reports suggested the involvement of numerous contributing factors including, mitochondrial dysfunction, oxidative stress, mitophagy, accumulation of somatic mtDNA mutations, compromised mitochondrial dynamics, and transport within axons in neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis. Therapies therefore target fundamental mitochondrial processes such as energy metabolism, free-radical generation, mitochondrial biogenesis, mitochondrial redox state, mitochondrial dynamics, mitochondrial protein synthesis, mitochondrial quality control, and metabolism hold great promise to develop pharmacological based therapies in NDD. By emphasizing the most efficient pharmacological strategies to target dysfunction of mitochondria in the treatment of neurodegenerative diseases, this review serves the scientific community engaged in translational medical science by focusing on the establishment of novel, mitochondria-targeted treatment strategies.

Abstract P3-05-18: Unravelling the clinicopathological and functional significance of Replication Protein A (RPA) heterotrimeric complex in sporadic breast cancers

Abstract Unravelling the clinicopathological and functional significance of Replication Protein A (RPA) heterotrimeric complex in sporadic breast cancers Mashael Algethami1, Michael S Toss 1,4, Juliette Brownlie 1, Corinne L Woodcock 1,2, Chandar Jaipal1, Ahmed Shoqafi 1, Katia A Mesquita1, Adel Alblihy1,3, Andrew R Green1, Nigel P Mongan 1,5, Emad A Rakha 1,4, Jennie N Jeyapalan 1,2 and Srinivasan Madhusudan1,6 1 Nottingham Biodiscovery Institute, Academic Unit for Translational Medical Sciences, School of Medicine, University of Nottingham, University Park, Nottingham NG7 2RD, UK. 2 Faculty of Medicine and Health Sciences, Centre for Cancer Sciences, University of Nottingham, Sutton Bonington Campus, Sutton Bonington, Leicestershire LE12 5RD, UK 3 Medical Center, King Fahad Security College (KFSC), Riyadh 11461, Saudi Arabia. 4 Department of Pathology, Nottingham University Hospital, City Campus, Hucknall Road, Nottingham NG5 1PB, UK. 5 Department of Pharmacology, Weill Cornell Medicine, New York, NY, 10065, USA 6 Department of Oncology, Nottingham University Hospitals, Nottingham NG5 1PB, UK. Introduction: Replication Protein A (RPA) is a critical single-stranded DNA (ssDNA)-binding protein that coats and protects exposed ssDNA from endogenous nucleases. RPA is a heterotrimeric complex consisting of RPA1 (70kDa), RPA2 (32kDa), and RPA3 (14kDa) subunits. RPA provides a platform for recruitment of factors required during replication, checkpoint regulation, DNA repair [including homologous recombination (HR), nucleotide excision repair (NER), base excision repair (BER) and mismatch repair (MMR)], telomere maintenance and retro-transposition. To understand the role of RPA in breast cancer pathogenesis we conducted a comprehensive genomic, transcriptomic, bioinformatic, proteomic and preclinical study. Patients and methods: RPA1, RPA2 and RPA3 protein expression was evaluated in 4221 primary invasive breast carcinomas and 776 breast ductal carcinoma in situ (DCIS). Transcriptomic investigation was completed in the METABRIC cohort (n=1980). Detailed bioinformatics was conducted in the TCGA cohort (n=1090). RPA deficient breast cancer cell lines were tested for Cisplatin, Palbociclib and Olaparib sensitivity. Results: RPA1, RPA2 and RPA3 loss is frequent in DCIS and linked to aggressive phenotype (including high grade, ER and PR negativity) (all p values < 0.01). DCIS with low RPA1 was also associated with poor local recurrence-free interval (p< 0.00001). In invasive breast cancers, low RPA1, low RPA2 and low RPA3 were all associated with larger size, lympho-vascular invasion, higher histological grade, high stage, ER negativity and poor breast cancer specific survival. Transcriptomic alterations in low RPA tumors included those genes involved in steroid hormone biosynthesis, chemical carcinogenesis, and drug metabolism. Pre-clinically, RPA deficient breast cancer cells were sensitive to Cisplatin and Palbociclib (CDK4/6 inhibitor) therapy compared to controls. Additionally, the PARP1 inhibitor Olaparib was synthetically lethal in RPA1 and RPA2 deficient cells compared to controls. Increased Olaparib sensitivity was associated with double strand breaks, S-phase cell cycle arrest and increased apoptosis. Conclusions: We provide the first comprehensive evidence that RPA loss is an early event during breast cancer pathogenesis and promotes aggressive phenotypes. Pre-clinically RPA deficient breast cancer cells were selectively toxic to Cisplatin, Palbociclib and Olaparib. Citation Format: Mashael A. Algethami, Michael Toss, Juliette Brownlie, Corinne L. Woodcock, Chandar Jaipal, AHMED SHOQAFI, Katia Mesquita, Adel Alblihy, Nigel Mongan, Emad Rakha, Jennie N. Jeyapalan, Srinivasan Madhusudan, Andrew R. Green. Unravelling the clinicopathological and functional significance of Replication Protein A (RPA) heterotrimeric complex in sporadic breast cancers [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-18.

Translational proteomics and phosphoproteomics: Tissue to extracellular vesicles.

We are currently experiencing a rapidly developing era in terms of translational and clinical medical sciences. The relatively mature state of nucleic acid examination has significantly improved our understanding of disease mechanism and therapeutic potential of personalized treatment, but misses a large portion of phenotypic disease information. Proteins, in particular phosphorylation events that regulates many cellular functions, could provide real-time information for disease onset, progression and treatment efficacy. The technical advances in liquid chromatography and mass spectrometry have realized large-scale and unbiased proteome and phosphoproteome analyses with disease relevant samples such as tissues. However, tissue biopsy still has multiple shortcomings, such as invasiveness of sample collection, potential health risk for patients, difficulty in protein preservation and extreme heterogeneity. Recently, extracellular vesicles (EVs) have offered a great promise as a unique source of protein biomarkers for non-invasive liquid biopsy. Membranous EVs provide stable preservation of internal proteins and especially labile phosphoproteins, which is essential for effective routine biomarker detection. To aid efficient EV proteomic and phosphoproteomic analyses, recent developments showcase clinically-friendly EV techniques, facilitating diagnostic and therapeutic applications. Ultimately, we envision that with streamlined sample preparation from tissues and EVs proteomics and phosphoproteomics analysis will become routine in clinical settings.

Therapeutic Effects of Butyrate on Pediatric Obesity

The pediatric obesity disease burden imposes the necessity of new effective strategies. To determine whether oral butyrate supplementation as an adjunct to standard care is effective in the treatment of pediatric obesity. A randomized, quadruple-blind, placebo-controlled trial was performed from November 1, 2020, to December 31, 2021, at the Tertiary Center for Pediatric Nutrition, Department of Translational Medical Science, University of Naples Federico II, Naples, Italy. Participants included children aged 5 to 17 years with body mass index (BMI) greater than the 95th percentile. Standard care for pediatric obesity supplemented with oral sodium butyrate, 20 mg/kg body weight per day, or placebo for 6 months was administered. The main outcome was the decrease of at least 0.25 BMI SD scores at 6 months. The secondary outcomes were changes in waist circumference; fasting glucose, insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, ghrelin, microRNA-221, and interleukin-6 levels; homeostatic model assessment of insulin resistance (HOMA-IR); dietary and lifestyle habits; and gut microbiome structure. Intention-to-treat analysis was conducted. Fifty-four children with obesity (31 girls [57%], mean [SD] age, 11 [2.91] years) were randomized into the butyrate and placebo groups; 4 were lost to follow-up after receiving the intervention in the butyrate group and 2 in the placebo group. At intention-to-treat analysis (n = 54), children treated with butyrate had a higher rate of BMI decrease greater than or equal to 0.25 SD scores at 6 months (96% vs 56%, absolute benefit increase, 40%; 95% CI, 21% to 61%; P < .01). At per-protocol analysis (n = 48), the butyrate group showed the following changes as compared with the placebo group: waist circumference, -5.07 cm (95% CI, -7.68 to -2.46 cm; P < .001); insulin level, -5.41 μU/mL (95% CI, -10.49 to -0.34 μU/mL; P = .03); HOMA-IR, -1.14 (95% CI, -2.13 to -0.15; P = .02); ghrelin level, -47.89 μg/mL (95% CI, -91.80 to -3.98 μg/mL; P < .001); microRNA221 relative expression, -2.17 (95% CI, -3.35 to -0.99; P < .001); and IL-6 level, -4.81 pg/mL (95% CI, -7.74 to -1.88 pg/mL; P < .001). Similar patterns of adherence to standard care were observed in the 2 groups. Baseline gut microbiome signatures predictable of the therapeutic response were identified. Adverse effects included transient mild nausea and headache reported by 2 patients during the first month of butyrate intervention. Oral butyrate supplementation may be effective in the treatment of pediatric obesity. ClinicalTrials.gov Identifier: NCT04620057.

Is There a Role for Genetic Testing in Patients With Myocarditis?

HomeCirculation: Genomic and Precision MedicineVol. 15, No. 5Is There a Role for Genetic Testing in Patients With Myocarditis? No AccessArticle CommentaryRequest AccessFull TextAboutView Full TextView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialNo AccessArticle CommentaryRequest AccessFull TextIs There a Role for Genetic Testing in Patients With Myocarditis? Emanuele Monda and Giuseppe Limongelli Emanuele MondaEmanuele Monda https://orcid.org/0000-0001-9304-988X Inherited and Rare Cardiovascular Diseases, Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy (E.M., G.L.). Search for more papers by this author and Giuseppe LimongelliGiuseppe Limongelli Correspondence to: Giuseppe Limongelli, MD, PhD, FESC Inherited and Rare Cardiovascular Disease Clinic Department of Translational Medical Sciences University of Campania “Luigi Vanvitelli” Via L. Bianchi 1 c/o Monaldi Hospital, AORN Colli Naples, 80131 Italy. Email E-mail Address: [email protected] https://orcid.org/0000-0002-8291-9517 Inherited and Rare Cardiovascular Diseases, Department of Translational Medical Sciences, University of Campania “Luigi Vanvitelli”, Naples, Italy (E.M., G.L.). Institute of Cardiovascular Sciences, University College of London and St. Bartholomew’s Hospital, London, United Kingdom (G.L.). Search for more papers by this author Originally published29 Sep 2022https://doi.org/10.1161/CIRCGEN.122.003824Circulation: Genomic and Precision Medicine. 2022;15FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCGEN.122.003824For Sources of Funding and Disclosures, see page 478.Correspondence to: Giuseppe Limongelli, MD, PhD, FESC Inherited and Rare Cardiovascular Disease Clinic Department of Translational Medical Sciences University of Campania “Luigi Vanvitelli” Via L. Bianchi 1 c/o Monaldi Hospital, AORN Colli Naples, 80131 Italy. Email [email protected]it

Abstracts from the ISSAID 2021 Periodic Congress

Abstracts from the ISSAID 2021 Periodic Congress

Pharmacological advances in mitochondrial therapy

Mitochondria play a vital role in cellular metabolism and are central mediator of intracellular signalling, cell differentiation, morphogenesis and demise. An increasingly higher number of pathologies is linked with mitochondrial dysfunction, which can arise from either genetic defects affecting core mitochondrial components or malfunctioning pathways impairing mitochondrial homeostasis. As such, mitochondria are considered an important target in several pathologies spanning from neoplastic to neurodegenerative diseases as well as metabolic syndromes. In this review we provide an overview of the state-of-the-art in mitochondrial pharmacology, focusing on the novel compounds that have been generated in the bid to correct mitochondrial aberrations. Our work aims to serve the scientific community working on translational medical science by highlighting the most promising pharmacological approaches to target mitochondrial dysfunction in disease.

Vitamin A in Children Hospitalized for Measles in a High-Income Country

Background: Worldwide medical authorities recommend vitamin A supplementation for severe measles requiring hospitalization; however, evidence supporting its use in high-income countries is lacking. A nationwide vitamin A shortage reported in concomitance with a recent measles outbreak in Italy provided an opportunity to test the effectiveness of vitamin A in a high-income setting, simulating a random allocation to treatment. Methods: We conducted a prospective controlled cohort study involving children admitted to a tertiary-care hospital in Southern Italy. The primary outcome was the duration of fever· Secondary outcomes included the length of hospitalization, rate of complications, need for antibiotic treatment, and body temperature. The study has been registered to the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance ( EU PAS 31805). Findings: A total of 108 inpatient children (36% females, median age 16·3 months) were enrolled; 36 received two doses of oil-based vitamin A according to age, and 72 matched controls received standard care. There were no significant differences between the study groups in the duration of fever (7·03±2·67 vs· 6·82±3·27, p=0·74), length of hospitalization (median, 5·5 vs· 5·0 days, p=0·36), maximum body temperature (median, 39°C in both groups, p=0·90), rate of organ (69·4% vs· 63·9%, p=0·56) and hematological complications (41·7% vs· 59·7%, p=0·07), or the need for antibiotic treatment (66·7% vs· 61·1%, p=0·57). Overall, vitamin A supplementation did not reduce the risk of any complications (relative risk, 1·33; 95% confidence intervals 0·59 to 2·96). Sub-group analysis in children with chronic conditions, weight-for-age <2 SD, known measles contact, or receiving care within 48h of fever did not demonstrate effectiveness of vitamin A over standard care. Interpretation: Vitamin A does not change the clinical course of measles virus infection or the rate of complications in children hospitalized in a high-income country. Trial Registration: The study has been registered to the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP®). Funding Statement: Department of Translational Medical Sciences, University of Naples Federico II. Declaration of Interests: The authors stated that there were no conflicts of interest to declare. Ethics Approval Statement: The study protocol was approved by the “Ethical Committee Federico II” of the University of Naples, Italy. Patients’ caregivers signed specific informed consent, and all patients’ data were analyzed and reported anonymously by using a single patient code.

How Translational Medicine Is Progressively Redefining Healthcare: From Bench to Bedside, the Patient Is the Bedrock of Translational Research

Translational medicine or translation research is an umbrella term that covers specific research in biological sciences whose main goal is to increase human life expectancy by keeping us healthy (from better ideas to better health). It’s synonymous with translational medical science, disease-targeted research, or evidence-based research. Translation research is particular because of its bidirectional nature. It’s commonly called the B2B approach or bench to bedside approach because it incorporates clinical skills and observations as well as scientific hypotheses utilized by researchers in the laboratories. The whole concept functions in a loop: bench to bedside and back. It translates knowledge, skills, or science from one place to another not only by focusing on the traditional 4P-Medicine – personalization, prevention, prediction, and participation – but also by taking into consideration another 3 Ps: providing (staff training), preemptive (research and development), and point of care (making sure that healthcare can be given anytime anywhere). Because of that, translational medicine can be viewed as a paradigm shift. This revolutionary concept shows how research discoveries can translate into effective therapies… Moreover, the understanding of disease pathology and preclinical models (their availability, their relevance to the disease and their translatability are considered key focus of modern translation research or translational medicine. Disease pathology may differ from one individual to the next. Researchers in the biological and the medical fields understand that. Thus, today, pharmacogenomics or personalized medicine is a field in the making and is set to revolutionized how patients are treated because the one size fits all approach is becoming more and more a thing of the past. Disease pathology also prompts researchers to consider our genetic makeups or our DNA first thing when trying to invent drugs or medical techniques likely to improve or enhance life expectancy.

HIGH HE4 CYSTIC FLUID/SERUM RATIO: A PREDICTOR OF MALIGNANCY IN PANCREATIC CYSTIC LESION? A CASE REPORT.

26Jul 2017 HIGH HE4 CYSTIC FLUID/SERUM RATIO: A PREDICTOR OF MALIGNANCY IN PANCREATIC CYSTIC LESION? A CASE REPORT. Vincenzo Napolitano , Claudia Mazzarella , Augusta Moccia , Manuela Avellino , Melania D?Anna , Giuseppe Perruolo , Giuseppe Portella and Daniela Terracciano. Department of Anaesthesiology, Surgery and Emergency Sciences, Second University of Naples, Italy. Department of Translational Medical Sciences, University of Naples Federico II, Italy. Department of Public Health, Pathology Division, University of Naples Federico II, Italy.

The Role of Simulation in Surgical Education.

The current healthcare environment demands optimization of patient outcomes in addition to maximal cost efficiency. Restrictions on resident work hours have placed limitations on the amount of time that trainee physicians can spend on patient care. For the surgery resident, the consequence is less time spent in the operating room under the supervision of a senior surgeon, the cornerstone of Halsted's approach to resident surgeon education. The use of simulation in graduate medical education has gained significant traction as a way to provide trainees with exposure to various techniques and procedures before use on the general patient population. This article describes simulation-based education with particular attention to surgical education. It proceeds to address competency-based education and mastery learning (ML) as key features of effective surgery education programs. A case study of ML in surgery is presented along with examples of translational medical education science from other medical specialties. The report concludes with a brief discussion about simulation-based surgical education today and prospects for the future.

Inflammatory Immune Infiltration in Human Tumors: Role in Pathogenesis and Prognostic and Diagnostic Value.

The cellular microenvironment directly and indirectly influences tumor development and possesses prognostic and in some cases diagnostic value. Over the years, understanding of structural organization of the immune/inflammatory moiety of neoplasms as well as in-depth phenotypic and transcriptomic profiling of its cellular components together provide more and more insights in both basic and translational medical science. In this review, we will discuss the specific roles of various stromal cells and their impact on neoplastic progression as well as address the use of quantitative and phenotypic analysis of immune/inflammatory infiltrate for diagnostics and predicting the clinical course of human malignancies.

Translational medical science

Translational medical science

Orientations and outcome of interdisciplinary research: the case of research behaviour in translational medical science

The importance of interdisciplinary research in accelerating the progress and commercialization of science is widely recognized, yet little is known about how academic research self-organizes towards interdisciplinarity. In this paper, we therefore explore the micro-level behavior of researchers as they venture into a promising space for interdisciplinary research, namely translational research--a bridge between basic and applied biomedical research. More specifically, we ask (1) whether the researchers who choose to engage in translational research have a strong scientific record, (2) how interdisciplinary research spanning basic and applied research influences the output of academic research, and (3) how different disciplinary distance in interdisciplinary research contributes to reputational benefits of researchers. We find that for some types of collaboration, interdisciplinarity results in more highly cited research, while in others it is not, and look for explanations for this difference. Our results show that translational research draws higher citations when it involves university researchers from the most basic end of the disciplinary spectrum, and when its issues are directed at basic (rather than applied) research.

Epigenetic mechanisms elicited by butyrate in peripheral blood mononuclear cells from children with IGE-mediated cow milk allergy

L. Paparo1,∗, R. Nocerino1, R. Aitoro1, V. Granata1, L. Cosenza1, I. Langella1, A. Amoroso1, G. Gioielli 1, R. Berni Canani2 1 Department of Translational Medical Science, University of Naples “Federico II”, Naples, Italy 2 Department of Translational Medical Science and European Laboratory for the Investigation of Food-Induced Diseases and CEINGE Advanced Biotechnologies, University of Naples “Federico II”, Naples, Italy

Bench-to-bedside translation of magnetic nanoparticles.

Magnetic nanoparticles (MNPs) are a new and promising addition to the spectrum of biomedicines. Their promise revolves around the broad versatility and biocompatibility of the MNPs and their unique physicochemical properties. Guided by applied external magnetic fields, MNPs represent a cutting-edge tool designed to improve diagnosis and therapy of a broad range of inflammatory, infectious, genetic and degenerative diseases. Magnetic hyperthermia, targeted drug and gene delivery, cell tracking, protein bioseparation and tissue engineering are but a few applications being developed for MNPs. MNPs toxicities linked to shape, size and surface chemistry are real and must be addressed before clinical use is realized. This article presents both the promise and perils of this new nanotechnology, with an eye towards opportunity in translational medical science.

A Balanced Look at the Implications of Genomic (and Other "Omics") Testing for Disease Diagnosis and Clinical Care.

The tremendous increase in DNA sequencing capacity arising from the commercialization of “next generation” instruments has opened the door to innumerable routes of investigation in basic and translational medical science. It enables very large data sets to be gathered, whose interpretation and conversion into useful knowledge is only beginning. A challenge for modern healthcare systems and academic medical centers is to apply these new methods for the diagnosis of disease and the management of patient care without unnecessary delay, but also with appropriate evaluation of the quality of data and interpretation, as well as the clinical value of the insights gained. Most critically, the standards applied for evaluating these new laboratory data and ensuring that the results and their significance are clearly communicated to patients and their caregivers should be at least as rigorous as those applied to other kinds of medical tests. Here, we present an overview of conceptual and practical issues to be considered in planning for the integration of genomic methods or, in principle, any other type of “omics” testing into clinical care.

Tailoring therapy for heart failure: the pharmacogenomics of adrenergic receptor signaling

Heart failure is one of the leading causes of mortality in Western countries, and β-blockers are a cornerstone of its treatment. However, the response to these drugs is variable among individuals, which might be explained, at least in part, by genetic differences. Pharmacogenomics is the study of genetic contributions to drug response variability in order to provide evidence for a tailored therapy in an individual patient. Several studies have investigated the pharmacogenomics of the adrenergic receptor system and its role in the context of the use of β-blockers in treating heart failure. In this review, we will focus on the most significant polymorphisms described in the literature involving adrenergic receptors and adrenergic receptor-related proteins, as well as genetic variations influencing β-blocker metabolism.

Small intestinal bacterial overgrowth and cystic fibrosis: Epidemiology, clinical impact and efficacy of rifaximin therapy

s / Digestive and Liver Disease 46 (2014) e85–e127 e89 style GFD were analysed. A core salivary microbiota of Saharawi T-CD children before and after Italian-style GFDwas identified and compared to Italian T-CD and healthy children (HC). Results: We found significant (P<0.05; FDR<0.05) differences in the salivary microbiota and metabolome between African and Italian-style GFD. Compared to Italian T-CD children, salivary samples of Saharawi T-CD children under African GFD were characterized for the unusual presence of Clostridia and for a high abundance of some other Firmicutes, Actinobacteria and Tenericutes genera. Italian GFD positively affected the abundance of Granulicatella, Porphyromonas and Neisseria. On the contrary, Clostridium, Prevotella and Veillonella strongly decreased after 60 days of Italian GFD. The OTU co-occurrence/exclusion pattern was identified and strong correlations (P<0.05; FDR<0.05) were found between the core bacterial genera and volatile organic compounds (VOC). During Italian GFD, Saharawi T-CD children strongly increased the amount of VOC, especially, acetone and 2-butanone. Conclusions: The insightsgleanedshouldhelp tofindingdietary implementation to improve health status of Saharawi T-CD children, and provide the first strong evidence for the effect of the diet on the human microbiota and metabolome. http://dx.doi.org/10.1016/j.dld.2014.07.063 ORAL ADMINISTRATION OF BUTYRATE PROTECTS AGAINST SENSITIZATION TO COW MILK PROTEIN IN A MURINE MODEL OF COW MILK ALLERGY Margherita Di Costanzo1,∗, Rosita Aitoro1, Lorella Paparo1, Andrew T. Stefka2, Tiffany J. Patton3, Rita Nocerino1, Antonio Calignano4, Rosaria Meli4, Giuseppina Mattace Raso4, Raffaele Simeoli4, Stefano Guandalini3, Cathryn Nagler2, Roberto Berni Canani1 1 Department of Translational Medical Science Pediatric Section, European Laboratory for the Investigation of Food-Induced Diseases, Federico II, Italy 2 Department of Pathology, University of Chicago, IL, USA 3 Department of Pediatric Gastroenterology, University of Chicago, IL, USA 4 Department of Pharmacy, University of Naples,