Exploring human gut microbiome variations across life: from eubiosis to dysbiosis in Western populations

The human gut microbiome (GM) is an extremely dynamic ecosystem, able to establish peculiar configurations in response to endogenous and exogenous stimuli – ageing, diet, lifestyle, disease. To explore microbiome-host relationship and unravel GM variations throughout the human lifespan, we studied specific functional aspects related to eubiosis and dysbiosis in Western populations using next-generation sequencing approaches, and developed a versatile murine model of intestinal inflammation to better explore the transition towards dysbiotic layouts. As for the aspects related to eubiotic microbiota configurations, we characterized age-related GM functional changes across life up to extreme longevity (22-109 years), highlighting life-long adaptive responses potentially supporting a new homeostasis. When compared to traditional populations – whose lifestyle resembles that of our ancestors – the Western GM is characterized by reduced biodiversity and supposed to contribute to the rising incidence of non-communicable diseases (NCDs). Consequently, we assessed the possibility to modulate the Western GM towards a more ‘ancestral’ configuration through a dietary intervention with a modern Paleolithic diet. Focusing on dysbiotic variations, we investigated links between diet, GM and obesity. Through a 4-year prospective study, we identified early markers and individual microbiome-host-diet configurations as a potential predictor related to the onset of the disease during childhood. Metagenomic and metatranscriptomic approaches were merged to unravel specific obese-related GM layouts and metabolic activities possibly associated with food addiction in obese women. The shift towards a dysbiotic microbiome structure and its association with several diseases have made the GM a strategic therapeutic target, paving the way for the development of a wide range of microbiome-tailored intervention strategies aimed at the restoration of eubiotic, health-promoting layouts. In this perspective, we developed a murine model of intestinal inflammation and provided researchers with a versatile tool for testing anti-inflammatory agents and/or new microbiome modulators such as classic or next-generation probiotics

The androgen-thyroid hormone crosstalk in prostate cancer and the clinical implications

: There is increasing evidence that thyroid hormones (THs) work in an integrative fashion with androgen receptors (ARs) to regulate gonadal differentiation and reproductive function. Studies reveal that THs have interactions with the AR promoter region and increase AR expression. THs also have a role in the regulation of enzymes involved in the biosynthesis of androgens, such as 5α-reductase, which is essential in the conversion of testosterone into its active form, 5α-dihydrotestosterone. Additionally, the presence of androgen response elements (AREs) in the promoter regions of TH-related genes, such as deiodinases and thyroid hormone receptor isoforms have been identified in some vertebrates, indicating a mutual interaction between THs and ARs. Since the androgen signaling pathway, mediated by ARs, plays a key role in the formation and progression of prostate cancer (PCa), the existence of crosstalk between THs and ARs supports the epidemiologic and experimental evidence indicating a relationship between the high incidence of Prostate Cancer (PCa) and hyperthyroidism. This article aims to review the role of androgen-thyroid hormone crosstalk in PCa and its implication in the clinical management. As life expectancy is growing these days, it can increase the number of patients with PCa and the critical relevance of the disease. In order to gain better knowledge about PCa and to improve the clinical management, it is essential to get better insight into the key factors related to the formation and progression of this cancer

Predicting Commercial Pilot Training Performance: A Validation Study

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Predicting Commercial Pilot Training Performance: A Validation Study

Accepted manuscript version, licensed CC BY-NC-ND 4.0. The main purpose of this study was to examine the predictive validity of the system used for ab initio selection of candidates to a bachelor program in aviation. The selection includes paper-and-pencil tests, computer-based tests, and an interview. A total of 188 candidates participated in the validation study. The total test score predicted the results of three exams in aviation theory (r = .27–.38) and extra flying hours needed (−.22), but not mean university grade. The regression analyses indicated that all predictors (tests and interview ratings) explained 25% of the variance in aviation theory, 19% in extra flying hours needed, and 7% in mean university grade. The overall findings confirmed the predictive validity of selection tests, especially the computer-based tests

Influence of Lactobacillus kefiri on Intestinal Microbiota and Fecal IgA Content of Healthy Dogs

The increasing incidence of gastrointestinal tract pathologies in dogs and the worrisome topic of antibiotic resistance have raised the need to look for new therapeutic frontiers. Of these, the use of probiotics represents a potential therapeutic alternative. Lactobacillus kefiri (Lk) is a species of Lactobacillus isolated from kefir. Previous studies have demonstrated that its administration in mice downregulates the expression of proinflammatory mediators and increases anti-inflammatory molecules in the gut immune system. It also regulates intestinal homeostasis, incrementing immunoglobulin A (IgA) secretion. Since Lk has never been studied as a single probiotic in dogs, the aim of this study was to evaluate the safety of Lk in dogs, and its effect on IgA secretion and on intestinal microbiota composition. Ten healthy dogs without a history of gastrointestinal diseases were included. The dogs received Lk at a dose of 107 live microorganisms orally, once daily for 30 days. The fecal samples were tested before administration, in the middle, at the end, and 30 days after discontinuation. The IgA secretion concentration and the microbiota composition were evaluated on the fecal samples. The results in this study suggested that Lk did not influence the concentration of IgA, nor significant changes of the intestinal microbiota were observed during and after the treatment. Therefore, additional studies are needed to investigate if a higher daily dosage of Lk can influence the intestinal homeostasis of dogs

A Digital Process for Manufacturing Customized Trays for Dental-Whitening Treatments

This study presents an alternative process for designing and manufacturing customized trays for dental-whitening treatments. The process is based on a digitized approach consisting of three main stages: design of a reference model, its manufacturing by AM, and thermoforming of the tray. The aim of the study was to develop a high-performance tray, able to guarantee comfort, safety, and efficacy for whitening treatments. To evaluate the patient’s experience, some tests under real operating conditions were performed. Twenty people carried out a nighttime treatment of 14 days. Each patient was asked to assess the overall level of satisfaction and the comfort of the tray and its ability to retain the gel. Tooth whitening was also determined according to the VITAPAN scale. All patients involved in the study were satisfied and provided positive feedback about comfort and tightness of the tray. At the end of the treatment, 15 out of 20 patients achieved shade A1 on the VITAPAN scale. The mean improvement in color shades was about 7. These results confirmed the great potential of the proposed dental tray. Its use was proven to guarantee a high level of quality, flexibility, and customization of dental-whitening treatments, improving comfort, safety, and efficacy

Non-invasive Assessment of Fecal Stress Biomarkers in Hunting Dogs During Exercise and at Rest

Intense exercise causes to organisms to have oxidative stress and inflammation at the gastrointestinal (GI) level. The reduction in intestinal blood flow and the exercise-linked thermal damage to the intestinal mucosa can cause intestinal barrier disruption, followed by an inflammatory response. Furthermore, the adaptation to exercise may affect the gut microbiota and the metabolome of the biofluids. The aim of the present research was to evaluate the presence of a GI derangement in hunting dogs through a non-invasive sampling as a consequence of a period of intense exercise in comparison with samples collected at rest. The study included nine dogs that underwent the same training regime for hunting wild boar. In order to counterbalance physiological variations, multiple-day replicates were collected and pooled at each experimental point for each dog. The samples were collected immediately at rest before the training (T0), after 60 days of training (T1), after 60 days of hunting wild boar (T2), and finally, at 60 days of rest after hunting (T3). A number of potential stress markers were evaluated: fecal cortisol metabolites (FCMs) as a major indicator of altered physiological states, immunoglobulin A (IgA) as an indicator of intestinal immune protection, and total antioxidant activity [total antioxidant capacity (TAC)]. Since stool samples contain exfoliated cells, we investigated also the presence of some transcripts involved in GI permeability [occludin (OCLN), protease-activated receptor-2 (PAR-2)] and in the inflammatory mechanism [interleukin (IL)-8, IL-6, IL-1b, tumor necrosis factor alpha (TNF\u3b1), calprotectin (CALP), heme oxygenase-1 (HO-1)]. Finally, the metabolome and the microbiota profiles were analyzed. No variation in FCM and IgA content and no differences in OCLN and CALP gene expression between rest and training were observed. On the contrary, an increase in PAR-2 and HO-1 transcripts, a reduction in total antioxidant activity, and a different profile of microbiota and metabolomics data were observed. Collectively, the data in the present study indicated that physical exercise in our model could be considered a mild stressor stimulus

Diffusion and wave behaviour in linear Voigt model

A boundary value problem related to a third- order parabolic equation with a small parameter is analized. This equation models the one-dimensional evolution of many dissipative media as viscoelastic fluids or solids, viscous gases, superconducting materials, incompressible and electrically conducting fluids. Moreover, the third-order parabolic operator regularizes various non linear second order wave equations. In this paper, the hyperbolic and parabolic behaviour of the solution is estimated by means of slow time and fast time. As consequence, a rigorous asymptotic approximation for the solution is established

Polyphenol and Tannin Nutraceuticals and Their Metabolites: How the Human Gut Microbiota Influences Their Properties

Nutraceuticals have been receiving increasing attention in the last few years due to their potential role as adjuvants against non-communicable chronic diseases (cardiovascular disease, diabetes, cancer, etc.). However, a limited number of studies have been performed to evaluate the bioavailability of such compounds, and it is generally reported that a substantial elevation of their plasma concentration can only be achieved when they are consumed at pharmacological levels. Even so, positive effects have been reported associated with an average dietary consumption of several nutraceutical classes, meaning that the primary compound might not be solely responsible for all the biological effects. The in vivo activities of such biomolecules might be carried out by metabolites derived from gut microbiota fermentative transformation. This review discusses the structure and properties of phenolic nutraceuticals (i.e., polyphenols and tannins) and the putative role of the human gut microbiota in influencing the beneficial effects of such compounds

Early-life gut microbiota and neurodevelopment in preterm infants: a narrative review

Infants born preterm are at a high risk of both gut microbiota (GM) dysbiosis and neurodevelopmental impairment. While the link between early dysbiosis and short-term clinical outcomes is well established, the relationship with longterm infant health has only recently gained interest. Notably, there is a significant overlap in the developmental windows of GM and the nervous system in early life. The connection between GM and neurodevelopment was first described in animal models, but over the last decade a growing body of research has also identified GM features as one of the potential mediators for human neurodevelopmental and neuropsychiatric disorders. In this narrative review, we provide an overview of the developing GM in early life and its prospective relationship with neurodevelopment, with a focus on preterm infants. Animal models have provided evidence for emerging pathways linking early-life GM with brain development. Furthermore, a relationship between both dynamic patterns and static features of the GM during preterm infants’ early life and brain maturation, as well as neurodevelopmental outcomes in early childhood, was documented. Future human studies in larger cohorts, integrated with studies on animal models, may provide additional evidence and help to identify predictive biomarkers and potential therapeutic targets for healthy neurodevelopment in preterm infants