Can the FUT2 non-secretor phenotype associated with gut microbiota increase the children susceptibility for type 1 diabetes? A mini review

The global toll of type 1 diabetes (T1D) has steadily increased over the last decades. It is now widely acknowledged that T1D pathophysiology is more complex than expected. Indeed, a multifaceted interplay between genetic, metabolic, inflammatory and environmental factors exists that leads to heterogeneous clinical manifestations across individuals. Children with non-secretor phenotype and those affected by T1D share low abundance of bifidobacteria, low content of short-chain fatty acids, intestinal phosphatase alkaline and a high incidence of inflammatory bowel diseases. In this context, host-gut microbiota dyad may represent a relevant contributor to T1D development and progression due to its crucial role in shaping host immunity and susceptibility to autoimmune conditions. The FUT2 gene is responsible for the composition and functional properties of glycans in mucosal tissues and bodily secretions, including human milk. FUT2 polymorphisms may profoundly influence gut microbiota composition and host susceptibility to viral infections and chronic inflammatory disease. In this minireview, the possible interplay between mothers’phenotype, host FUT2 genetic background and gut microbiota composition will be discussed in perspective of the T1D onset. The study of FUT2-gut microbiota interaction may add a new piece on the puzzling T1D etiology and unveil novel targets of intervention to contrast T1D development and progression. Dietary interventions, including the intake of a-(1, 2)-fucosyl oligosaccharides in formula milk and the use of specific prebiotics and probiotics, could be hypothesized

Combination of metabolomic and proteomic analysis revealed different features among Lactobacillus delbrueckii subspecies bulgaricus and lactis strains while in vivo testing in the model organism Caenorhabditis elegans highlighted probiotic properties

Lactobacillus delbrueckii represents a technologically relevant member of lactic acid bacteria, since the two subspecies bulgaricus and lactis are widely associated with fermented dairy products. In the present work, we report the characterization of two commercial strains belonging to L. delbrueckii subspecies bulgaricus, lactis and a novel strain previously isolated from a traditional fermented fresh cheese. A phenomic approach was performed by combining metabolomic and proteomic analysis of the three strains, which were subsequently supplemented as food source to the model organism Caenorhabditis elegans, with the final aim to evaluate their possible probiotic effects. Restriction analysis of 16S ribosomal DNA revealed that the novel foodborne strain belonged to L. delbrueckii subspecies lactis. Proteomic and metabolomic approaches showed differences in folate, aminoacid and sugar metabolic pathways among the three strains. Moreover, evaluation of C. elegans lifespan, larval development, brood size, and bacterial colonization capacity demonstrated that L. delbrueckii subsp. bulgaricus diet exerted beneficial effects on nematodes. On the other hand, both L. delbrueckii subsp. lactis strains affected lifespan and larval development. We have characterized three strains belonging to L. delbrueckii subspecies bulgaricus and lactis highlighting their divergent origin. In particular, the two closely related isolates L. delbrueckii subspecies lactis display different galactose metabolic capabilities. Moreover, the L. delbrueckii subspecies bulgaricus strain demonstrated potential probiotic features. Combination of omic platforms coupled with in vivo screening in the simple model organism C. elegans is a powerful tool to characterize industrially relevant bacterial isolates

In vitro probiotic properties and in vivo anti-ageing effects of Lactoplantibacillus plantarum PFA2018AU strain isolated from carrots on Caenorhabditis elegans

Lactic acid bacteria (LAB) share and provide several beneficial effects on human health, such as the release of bioactive metabolites, pathogen competition, and immune stimulation. The two major reservoirs of probiotic microorganisms are the human gastro-intestinal tract and fermented dairy products. However, other sources, such as plant-based foods, represent important alternatives thanks to their large distribution and nutritive value. Here, the probiotic potential of autochthonous Lactiplantibacillus plantarum PFA2018AU, isolated from carrots harvested in Fucino highland, Abruzzo (Italy), was investigated through in vitro and in vivo approaches. The strain was sent to the biobank of Istituto Zooprofilattico Sperimentale della Lombardia ed Emilia Romagna in Italy for the purpose of patent procedures under the Budapest Treaty. The isolate showed high survival capability under in vitro simulated gastro-intestinal conditions, antibiotic susceptibility, hydrophobicity, aggregation, and the ability to inhibit the in vitro growth of Salmonella enterica serovar Typhimurium, Listeria monocytogenes, Pseudomonas aeruginosa, and Staphylococcus aureus pathogens. Caenorhabditis elegans was used as the in vivo model in order to analyse prolongevity and anti-ageing effects. L. plantarum PFA2018AU significantly colonised the gut of the worms, extended their lifespan, and stimulated their innate immunity. Overall, these results showed that autochthonous LAB from vegetables, such as carrots, have functional features that can be considered novel probiotic candidates

Olive mill wastes. A source of bioactive molecules for plant growth and protection against pathogens

Olive oil production generates high amounts of liquid and solid wastes. For a long time, such complex matrices were considered only as an environmental issue, due to their polluting properties. On the other hand, olive mill wastes (OMWs) exert a positive effect on plant growth when applied to soil due to the high content of organic matter and mineral nutrients. Moreover, OMWs also exhibit antimicrobial activity and protective properties against plant pathogens possibly due to the presence of bioactive molecules including phenols and polysaccharides. This review covers the recent advances made in the identification, isolation, and characterization of OMW-derived bioactive molecules able to influence important plant processes such as plant growth and defend against pathogens. Such studies are relevant from different points of view. First, basic research in plant biology may benefit from the isolation and characterization of new biomolecules to be potentially applied in crop growth and protection against diseases. Moreover, the valorization of waste materials is necessary for the development of a circular economy, which is foreseen to drive the future development of a more sustainable agriculture

Gut Microbiota Functional Traits, Blood pH, and Anti-GAD Antibodies Concur in the Clinical Characterization of T1D at Onset

Alterations of gut microbiota have been identified before clinical manifestation of type 1 diabetes (T1D). To identify the associations amongst gut microbiome profile, metabolism and disease markers, the 16S rRNA-based microbiota profiling and H-1-NMR metabolomic analysis were performed on stool samples of 52 T1D patients at onset, 17 T1D siblings and 57 healthy subjects (CTRL). Univariate, multivariate analyses and classification models were applied to clinical and -omic integrated datasets. In T1D patients and their siblings, Clostridiales and Dorea were increased and Dialister and Akkermansia were decreased compared to CTRL, while in T1D, Lachnospiraceae were higher and Collinsella was lower, compared to siblings and CTRL. Higher levels of isobutyrate, malonate, Clostridium, Enterobacteriaceae, Clostridiales, Bacteroidales, were associated to T1D compared to CTRL. Patients with higher anti-GAD levels showed low abundances of Roseburia, Faecalibacterium and Alistipes and those with normal blood pH and low serum HbA(1c) levels showed high levels of purine and pyrimidine intermediates. We detected specific gut microbiota profiles linked to both T1D at the onset and to diabetes familiarity. The presence of specific microbial and metabolic profiles in gut linked to anti-GAD levels and to blood acidosis can be considered as predictive biomarker associated progression and severity of T1D

Hyperbaric exposure and oxidative Stress in occupational activities (HEOxS): the study protocol

Background: Hyperbaric exposure (HE) is proven to be a stressor to several mechanisms in living cells. Even if after homeostasis restoration, harmful effects are expected, in particular a presence of free radicals. These latter are the stimulus to negative phenomenon as inflammation or cancer. In Italy, with 7500 km of sea shores, a large quantity of workers is exposed to HE during occupational activities. A deep knowledge of HE and bodily effects is not well defined; hence a multidisciplinary assessment of risk is needed. To detect one or more indicators of HE a research group is organised, under the INAIL sponsorship. The research project focused on the oxidative stress (OxS) and this paper details on the possible protocol to estimate, with a large amount of techniques on several human liquids, the relationship between OxS and HE. Specific attention will be paid to identify confounding factors and their influence. Methods: Blood and urine will be sampled. Several lab techniques will be performed on samples, both targeted, to measure the level of well-known biomarkers, and untargeted. Regard the formers: products of oxidation of DNA and RNA in urine; inflammation and temperature cytokines and protein carbonyles in blood. Untargeted evaluation will be performed for a metabolomics analysis in urine. Confounding factors: temperature, body fat, fitness, allergies and dietary habits. These factors will be assessed, directly or indirectly, prior and after HE. The final scope of the project is to determine one or more indicators that relates to HE in hits twofold nature: depth and duration. Conclusion: The relationship between OxS and HE is not deeply investigated and literature proposes diverging results. The project aims to define the time dependence of biomarkers related to OxS, to rise knowledge in risk assessment in workers exposed to HE

Phylogenetic and Metabolic Tracking of Gut Microbiota during Perinatal Development

The colonization and development of gut microbiota immediately after birth is highly variable and depends on several factors, such as delivery mode and modality of feeding during the first months of life. A cohort of 31 mother and neonate pairs, including 25 at-term caesarean (CS) and 6 vaginally (V) delivered neonates (DNs), were included in this study and 121 meconium/faecal samples were collected at days 1 through 30 following birth. Operational taxonomic units (OTUs) were assessed in 69 stool samples by phylogenetic microarray HITChip and inter- and intra-individual distributions were established by inter-OTUs correlation matrices and OTUs co-occurrence or co-exclusion networks. H-1-NMR metabolites were determined in 70 stool samples, PCA analysis was performed on 55 CS DNs samples, and metabolome/OTUs co-correlations were assessed in 45 CS samples, providing an integrated map of the early microbiota OTUs-metabolome. A microbiota "core" of OTUs was identified that was independent of delivery mode and lactation stage, suggesting highly specialized communities that act as seminal colonizers of microbial networks. Correlations among OTUs, metabolites, and OTUs-metabolites revealed metabolic profiles associated with early microbial ecological dynamics, maturation of milk components, and host physiology.Peer reviewe

Si può modificare il microbiota intestinale durante l’epoca perinatale?

L’influenza della flora intestinale sulla salute umana è continua dalla nascita alla vecchiaia. Il primo contatto con i batteri durante e immediatamente dopo la nascita ha un ruolo importante nello sviluppo della flora intestinale e successivamente sul sistema immunitario della mucosa del neonato. Il microbiota intestinale del neonato è correlato alla suscettibilità alle infezioni e alla sensibilizzazione ad antigeni ambientali nei primi anni di vita. La corretta successione nelle specie microbiche che colonizzano l’intestino del neonato nel primo periodo di vita determina una programmazione immunitaria e metabolica che ha un’influenza a lungo termine sul rischio di malattie. Ad esempio la nascita mediante parto cesareo sembra aumentare il rischio di malattia celiaca, diabete di tipo 1 e asma, che sono generalmente associati a risposte T helper eccessive o aberranti. È stato ipotizzato che il contatto tra microbiota materno e feto possa avvenire già a livello uterino. Quantità rilevabili di batteri o DNA batterico sono stati rilevati nella placenta sana come pure nelle membrane e nel liquido amniotico e questo contatto microbico, pur non ancora del tutto chiarito, è associato ad una risposta immunitaria sistemica nel neonato. La presenza di DNA microbico nella placenta potrebbe modulare significativamente l’immunità innata nell’ intestino fetale. La possibilità di modulare lo sviluppo e la composizione del microbiota intestinale allo scopo di migliorare la salute della madre e del bambino è alla base dell’utilizzo di probiotici. La somministrazione di probiotici alla madre nel periodo perinatale determina variazioni sul microbiota intestinale della donna che si riflettono in modifiche di fattori immunitari e del microbiota del neonato. Infatti l’assunzione di una miscela di lattobacilli e bifidobatteri (VSL#3) nell’ultimo mese di gravidanza e durante il primo mese di allattamento ha determinato nel latte materno un aumento significativo della concentrazione di IgA secretorie e citochine ad attività antinfiammatoria e immunomodulante come TGF-β e Il-10. Inoltre la concentrazione di lattobacilli e bifidobatteri del microbiota intestinale dei neonati allattati da madri che assumevano il probiotico è risultata maggiore rispetto ai neonati di madri di controllo (1). Anche l’assunzione del Lactobacillus GG da parte di madri finlandesi prima del parto e durante l’allattamento induceva la modulazione della colonizzazione e dello sviluppo di bifidobatteri nell’intestino dei loro bambini, in particolare aumentando la diversità delle specie di bifidobatteri (2). Inoltre la somministrazione alle madri durante le ultime settimane di gravidanza di probiotici contenenti un ceppo di lattobacilli ha determinato un’aumentata quantità di B. longum fecale nei neonati (3) e si è dimostrata efficace nel proteggere il bambino dalla dermatite atopica (4). Uno studio recente (5) ha dimostrato che l’assunzione orale di VSL#3 nell’ultimo trimestre di gravidanza è associato ad una modulazione del microbiota vaginale e della secrezione di citochine, con livelli significativamente più alti di IL-4 e IL-10, ad azione antiinfiammatoria, e riduzione della Eotassina, chemochina pro-infiammatoria. Tutto ciò potrebbe avere importanti implicazioni nella prevenzione delle infezioni vaginali e quindi del parto pretermine. In conclusione, alcuni probiotici, validati sul piano scientifico, somministrati alla madre durante la gravidanza e l’allattamento possono modulare il microbiota della madre e del neonato