55 research outputs found
The aryl hydrocarbon receptor pathway: a linking bridge between the gut microbiome and neurodegenerative diseases
No full textThe Aryl hydrocarbon receptor (AHR) is a cytosolic receptor and ligand-activated transcription factor widely expressed across various cell types in the body. Its signaling is vital for host responses at barrier sites, regulating epithelial renewal, barrier integrity, and the activities of several types of immune cells. This makes AHR essential for various cellular responses during aging, especially those governing inflammation and immunity. In this review, we provided an overview of the mechanisms by which the AHR mediates inflammatory response at gut and brain level through signals from intestinal microbes. The age-related reduction of gut microbiota functions is perceived as a trigger of aberrant immune responses linking gut and brain inflammation to neurodegeneration. Thus, we explored gut microbiome impact on the nature and availability of AHR ligands and outcomes for several signaling pathways involved in neurodegenerative diseases and age-associated decline of brain functions, with an insight on Parkinson's and Alzheimer's diseases, the most common neurodegenerative diseases in the elderly. Specifically, we focused on microbial tryptophan catabolism responsible for the production of several AHR ligands. Perspectives for the development of microbiota-based interventions targeting AHR activity are presented for a healthy aging
Biofilm Formation and Immunomodulatory Activity of Proteus mirabilis Clinically Isolated Strains. [Fusco A. and Coretti L. co-first authors]
No full textUrinary tract infections (UTIs) and catheter-associated UTIs (CAUTIs) are the principal hospital-acquired infections. Proteus mirabilis is characterized by several virulence factors able to promote adhesion and biofilm formation and ameliorate the colonization of urinary tract and the formation of crystalline biofilms on the abiotic surface of the urinary catheters. Since, to date, the role of P. mirabilis in the etiopathogenesis of different types of urinary tract infections is not well established, in this study we sought to characterize two different clinically isolated strains of P. mirabilis (PM1 and PM2) with distinctive phenotypes and analyzed various virulence factors possibly implicated in the ability to induce UTIs and CAUTIs. In particular, we analyzed motility, biofilm formation both on abiotic and biotic surfaces of PM1 and PM2 and paralleled these parameters with the ability to induce an inflammatory response in an epithelial cell model. Results showed that PM1 displayed major motility and a capacity to form biofilm and was associated with an anti-inflammatory response of host cells. Conversely, PM2 exhibited lack motility and a had slower organization in biofilm but promoted an increase of proinflammatory cytokine expression in infected epithelial cells. Our study provides data useful to start uncovering the pathologic basis of P. mirabilis-associated urinary infections. The evidence of different virulence factors expressed by PM1 and PM2 highlights the possibility to use precise and personalized therapies targeting specific virulence pathways
Botulinum Toxin A for controlling obesity
No full textRapid growth of the overweight population and the number of obese individuals in recent decades suggests that current strategies based on diet, exercise, and pharmacological knowledge are not sufficient to address this epidemic. Obesity is the result of a high caloric intake and energy storage, not counterbalanced by an equally important energy expense. Botulinum toxin type A (BoNT-A) use is rapidly expanding to include treatment of a variety of ophthalmological, gastrointestinal, urological, orthopedic, dermatological, secretory, painful, and cosmetic disorders. Many studies evaluating the effect of BoNT-A in gastric antrum e/o fundus for the treatment of obesity have been published. This treatment modality was based on the observation that gastric injection of BoNT-A in laparatomized rats induced a significant reduction of food intake and body weight. These studies have been published yielding debated results. Differences in the selection of patients, the doses of BoNT-A, the method of administration of the toxin, and the instruments of evaluation of some parameters among these studies may be the cause. In this review, it will study the state-of-the-art use of BoNT-A in obesity basic science models and review the clinical evidence on the therapeutic applications of BoNT-A for obesity
Epigenetic alterations induced by bacterial lipopolysaccharides
No full textLipopolysaccharide (LPS) is one of the principal bacterial products known to elicit inflammation. Cells of myeloid lineage such as monocytes and macrophages, but also epithelial cells give rise to an inflammatory response upon LPS stimulation. This phenomenon implies reprogramming of cell specific gene expression that can occur through different mechanisms including epigenetic modifications. Given their intrinsic nature, epigenetic modifications may be involved both in the acute response to LPS and in the establishment of a preconditioned genomic state (epigenomic memory) that may potentially influence the host response to further contacts with microorganisms. Information has accumulated during the last years aimed at elucidating the epigenetic mechanisms which underlie the cellular LPS response. These findings, summarized in this chapter, will hopefully be a good basis for a definition of the complete cascade of LPS-induced epigenetic events and their biological significance in different cell types
Autism spectrum disorder
No full textBackground: Autism spectrum disorder is a complex heterogeneous condition that is characterized by impairments in social interaction, communication, and behavior which mostly co-exists with several comorbidities. The current prevalence of autism spectrum disorder in the general population is estimated to be 1 in 68 children. Despite significant advances in research and multiple treatment options, the management of the disease remains poor. Although there are governmental services and few non-governmental organizations working for individuals with autism, there is no official data available regarding the incidence and prevalence of autism in Malta
Methods: This study focuses on the need of increasing awareness for autism spectrum disorder in Malta among the general public and health care professionals which would benefit a better understanding of the disorder for early diagnosis and more effective treatments. This was best provided through questionnaires.
Results: Our survey revealed that only a limited percentage of the Maltese population had some knowledge about the symptoms, age of onset, potential causes of the disease and treatment options for autism.
Conclusion: There is an immense need for improvement regarding the awareness of autism in Malta to estimate the exact burden of the disorder and make the latest diagnostic and treatment options available to the people living with this disease on the island
Insect-based diet, a promising nutritional source, modulates gut microbiota composition and SCFAs production in laying hens. [Borrelli L. and Coretti L. co-first authors]
No full textInsects could be potential nutritional sources both for humans and animals. Among these, Hermetia illucens, with good amount of chitin and proteins, represents a suitable diet replacement for laying hens. Little is known about insect diet effects on the microbial ecology of the gastrointestinal tract and bacterial metabolites production. In this study we investigated the effect of H. illucens larvae meal administration on cecal microbiota and short chain fatty acids (SCFAs) production in laying hens. 16S rDNA sequencing showed strong differences between cecal microbiota of soybean (SD) and insect diet (ID) groups both in type and relative abundance (unweighted and weighted beta diversity) of microbial species. In particular, Bacteroides plebeius, Elusimicrobium minutum, Alkaliphilus transvaalensis, Christensenella minuta, Vallitalea guaymasensis and Flavonifractor plautii represented the principal contributors of changes in gut microbiota composition of ID group (FDR p-values < 0.05). Of these, F. plautii, C. minuta and A. transvaalensis have the potential to degrade the chitin's insect meal and correlated with the observed high levels of gut SCFAs produced in ID group. These microorganisms may thus connect the chitin degradation with high SCFAs production. Our results suggest H. illucens as a potential prebiotic by well feeding gut microbiota
Gut Microbiota Features in Young Children with Autism Spectrum Disorders. [*Coretti L. corresponding author]
No full textProliferation and/or depletion of clusters of specific bacteria regulate intestinal functions and may interfere with neuro-immune communication and behavior in patients with autism spectrum disorder (ASD). Consistently, qualitative and quantitative alteration of bacterial metabolites may functionally affect ASD pathophysiology. Up to date, age-restricted cohort studies, that may potentially help to identify specific microbial signatures in ASD, are lacking. We investigated the gut microbiota (GM) structure and fecal short chain fatty acids (SCFAs) levels in a cohort of young children (2-4 years of age) with ASD, with respect to age-matched neurotypical healthy controls. Strong increase of Bacteroidetes and Proteobacteria and decrease of Actinobacteria was observed in these patients. Among the 91 OTUs whose relative abundance was altered in ASD patients, we observed a striking depletion of Bifidobacterium longum, one of the dominant bacteria in infant GM and, conversely, an increase of Faecalibacterium prausnitzii, a late colonizer of healthy human gut and a major butyrate producer. High levels of F. prausnitzii were associated to increase of fecal butyrate levels within normal range, and over representation of KEGG functions related to butyrate production in ASD patients. Here we report unbalance of GM structure with a shift in colonization by gut beneficial bacterial species in ASD patients as off early childhood
LPS INFECTION OF INTESTINAL EPITHELIAL CELLS INDUCES EXPRESSION OF COX-2 TROUGH EPIGENETIC MECHANISMS
No full textIntroduction: LPS induces the release of COX-2 by intestinal mucosal cells, because it is now emerging that bacteria may induce alteration of epigenetic patterns in host cells, we have investigated whether LPS induced COX-2 activation in human intestinal epithelial cells (HT-29) involves changes of histone modifications and/or DNA methylation at COX-2 gene regulatory region. We hypothesized that LPS infection may have a direct impact on the epigenetic status of COX-2 gene in HT-29 cells and that LPS-induced COX-2 activation may be mediated by rapid changes at COX-2 gene regulatory regions. LPS induces epigenetic events that include both chromatin and DNA methylation modifications after COX-2 activation in HT-29 cells.
Material e Methods: HT-29 treated with LPS and not were used for Relative Quantitative expression analysis in real time PCR. Quantitative ChIP analysis was performed on COX-2 promoter for histone modifications analysis. Gene silencing by RNA interference were used for determine the epigenetic mechanism of COX-2 activation LPS-dependent. DNA methylation analysis of COX-2 promoter was performed by MALDI-TOF.
Results: We described the chromatin and DNA methylation changes occurring at the COX-2 gene in HT-29 cells as direct consequences of LPS exposure. LPS infection is followed by several expression, chromatin and DNA modifica- tion events including: activation of the COX-2 gene; transient gradual increase of H3K4 dimethylation and decrease of H3K9 dimethylation and H3K27 trimethylation in correspondence of the later 2h peak of COX-2 mRNA expression; rapid cyclical DNA methylation/demethylation events at specific CpG sites at COX-2 gene-regulatory region mainly in concomitance with the early expression gene. Discussion e Conclusion: We have investigated the epigenetic changes occurring at the COX-2 locus during the first 24 h after exposure of human HT29 to LPS and, thus directly attributable to host-parasite interaction. 2h of LPS exposure of HT29 cells induces the JMJD3 binding to COX-2 promoter region and following removing of H3K27me3 associated to expression of COX-2. Most of chromatin marks are then restored in a short time after LPS infection with the exception of LSD1 that no longer bind to COX-2 promoter, possibly responsible of not H3K9me2 demethylation underlying a more condensed chromatin state at the COX-2 gene. In addiction, a cyclic DNA methylation/demethilation of COX-2 promoter, observed in LPS-HT29 cells treatment, can to be associated at stable expression of gene. It will be very important to investigate whether the observed decrease of JMJD3 levels at COX-2 in response to long treatment with LPS may occur in intestinal mucosa and may represent a stable epigenetic mark during long exposition to microorganisms
Spectroscopic identification and anti-biofilm properties of polar metabolites from the medicinal plant Helichrysum italicum against Pseudomonas aeruginosa
No full textTwo new acylated styrylpyrones, one 5-methoxy-1(3H)-isobenzofuranone glucoside and a hydroxymethyl-orcinol derivative, along with sixteen known aromatic metabolites, including lignans, quinic acid derivatives low-molecular weight phenol glucosides, have been isolated from the methanol extract of Helichrysum italicum, a medicinal plant typical of the Mediterranean vegetation. The structures of these compounds have been elucidated on the basis of extensive 2D-NMR spectroscopic analyses, including COSY, TOCSY, HSQC, CIGAR-HMBC, H2BC and HSQC-TOCSY, along with Q-TOF HRMS(2) analysis. Selected compounds were evaluated for their anti-biofilm properties against Pseudomonas aeruginosa
The Interplay between Defensins and Microbiota in Crohn's Disease
No full textCrohn's disease (CD) is a chronic inflammation of the intestinal mucosa, characterized by periods of acute recurrence and remission. Depending on the specific region affected, CD is classified as ileal CD or colonic CD. It is largely accepted that the intestinal microbiota is involved in the onset of the pathology. Indeed, a reduced immune tolerance to components of the intestinal commensal microbiota and inflammation of the intestinal barrier typifies patients with CD. Several studies have shown defective expression of intestinal antimicrobial peptides (AMPs) in patients with CD compared to controls, particularly defensins. A reduction in α-defensins is observed in ileal CD, while β-defensins are increased in colonic CD. In addition to an immunological basis, the disease is frequently associated with genetic alterations including mutations of NOD2 gene. Several therapeutic strategies to circumvent the dysfunction observed in CD are currently under investigation. These include the use of delivery systems to administer endogenous AMPs and the engineering of peptidomimetics that could ameliorate the severity of CD. In this review, the role defensins play in CD and the strategies aimed at overcoming bacterial resistance will be discussed
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