Dynamic microbial and metabolic changes during Apulian Caciocavallo cheese-making and ripening produced according to a standardized protocol.

The cheese microbiota plays a critical role in influencing its sensory and physicochemical properties. In this study, traditional Apulian Caciocavallo cheese coming from 4 different dairies in the same area and produced following standardized procedures have been examined, as well as the different bulk milks and natural whey starter cultures used. Moreover, considering the cheese wheels as the blocks of Caciocavallo cheeses as whole, these were characterized at different layers (i.e., core, under-rind, and rind) of the block using a multi-omics approach. In addition to physical-chemical characterization, culturomics, quantitative PCR, metagenomics, and metabolomics analysis, have been carried out post-salting and throughout ripening time (2 mo) to investigate the major shifts in the succession of the microbiota and flavor development. Culture-dependent and 16S rRNA metataxonomics results clearly clustered samples based on the microbiota biodiversity related to the production dairy plant as the result of the use of different NWS or intrinsic conditions of each production site. At the beginning of the ripening, cheeses were dominated by the Lactobacillus and, in 2 dairies (Art and SdC), Streptococcus genera associated with the NWS. The analysis allowed us to show that, although the diversity of identified genera did not change significantly between the rind, under-rind and core fractions of the same samples, there was an evolution in the relative abundance and absolute quantification, modifying and differentiating profiles during ripening. The qPCR mainly differentiated the temporal adaptation of those species originating from bulk milks and those provided by NWSs. The primary starter detected in NWS and cheese reassured the high relative concentration of 1-butanol, 2-butanol, 2-heptanol, 2-butanone, acetoin, delta-dodecalactone, hexanoic acid ethyl ester, octanoic acid ethyl ester, and VFFA during ripening, while cheeses displaying low abundances of Streptococcus and Lactococcus (dairy Del) have a lower total concentration of acetoin compared with Art and SdC. However, the sub-dominant strains and NSLAB present in cheeses are responsible for the production of secondary metabolites belonging to the chemical classes of ketones, alcohols, and organic acids, reaffirming the importance and relevance of autochthonous strains of each dairy plant although considering a delimited production area.

Exploring the Gut Microbiome and Metabolome in Individuals with Alopecia Areata Disease.

In recent years, heightened attention has been devoted to unravelling the intricate interplay between genetic and environmental factors shaping the gut microbiota and its significance for human health. This study delves into exploring the plausible connection between Alopecia Areata (AA), an autoimmune disease, and the dynamics of the gut microbiome. Examining a cohort of healthy adults and individuals with AA, both the gut microbiota composition and volatile organic compound (VOC) metabolites from faeces and urine were analysed. While overall microbiota composition showed no significant differences, intra-individual variability revealed distinctions related to age, gender, and pathology status, with AA individuals exhibiting reduced species richness and evenness. Differential abundance analysis identified microbial biomarkers for AA, notably Firmicutes, Lachnospirales, and Blautia, while Coprococcus stood out for healthy individuals. The Data Integration Analysis for Biomarker discovery using Latent Components (DIABLO) method further supported these findings including metabolite biomarkers, such as esters of branched chain fatty acids and branched chain amino acids as predictors for AA, suggesting potential links to oxidative stress. Despite certain limitations, the study highlights the complexity of the gut microbiome and its metabolites in the context of AA, while the biomarkers identified could be useful starting points for upcoming studies.

Functional and Therapeutic Potential of Cynara scolymus in Health Benefits.

Dietary supplements enriched with bioactive compounds represent a promising approach to influence physiological processes and enhance longevity and overall health. Cynara cardunculus var. scolymus serves as a functional food supplement with a high concentration of bioactive compounds, which offers various health-promoting benefits. Several chronic diseases have metabolic, genetic, or inflammatory origins, which are frequently interconnected. Pharmacological treatments, although effective, often result in undesirable side effects. In this context, preventive approaches are gaining increased attention. Recent literature indicates that the consumption of bioactive compounds in the diet can positively influence the organism's biological functions. Polyphenols, well-known for their health benefits, are widely recognized as valuable compounds in preventing/combating various pathologies related to lifestyle, metabolism, and aging. The C. scolymus belonging to the Asteraceae family, is widely used in the food and herbal medicine fields for its beneficial properties. Although the inflorescences (capitula) of the artichoke are used for food and culinary purposes, preparations based on artichoke leaves can be used as an active ingredient in herbal medicines. Cynara scolymus shows potential benefits in different domains. Its nutritional value and health benefits make it a promising candidate for improving overall well-being. C. scolymus exhibits anti-inflammatory, antioxidant, liver-protective, bile-expelling, antimicrobial, and lipid-lowering neuroprotective properties. Different studies demonstrate that oxidative stress is the leading cause of the onset and progression of major human health disorders such as cardiovascular, neurological, metabolic, and cancer diseases. The large amount of polyphenol found in C. scolymus has an antioxidant activity, enabling it to neutralize free radicals, preventing cellular damage. This reduces the subsequent risk of developing conditions such as cancer, diabetes, and cardiovascular diseases. Additionally, these polyphenols demonstrate anti-inflammatory activity, which is closely associated with their antioxidant properties. As a result, C. scolymus has the potential to contribute to the treatment of chronic diseases, including intestinal disorders, cardiovascular diseases, and neurodegenerative pathologies. The current review discussed the nutritional profiles, potential benefits, and pharmacological effects of C. scolymus.

Molecular Simulations of Hydrogen Sorption in Semicrystalline High-Density Polyethylene: The Impact of the Surface Fraction of Tie-Chains.

The modeling of the barrier properties of semicrystalline polymers has gained interest following the possible application of such materials as protective liners for the safe supply of pressurized hydrogen. The mass transport in such systems is intimately related to the complex intercalation between the crystal and amorphous phases, which was approached in this work through an all-atom representation of high-density polyethylene structures with a tailored fraction of amorphous-crystalline connections (tie-chains). Simulations of the polymer pressure-volume-temperature data and hydrogen sorption were performed by means of molecular dynamics and the Widom test particle insertion method. The discretization of the simulation domains of the semicrystalline structures allowed us to obtain profiles of density, degree of order, and gas solubility. The results indicated that the gas sorption in the crystalline regions is negligible and that the confinement of the amorphous phase between crystals induces a significant increase in density and a drop in the sorption capacity, even in the absence of tie-chains. Adding ties between the crystal and the amorphous phase results in further densification, an increase of the lamella tilt angle, and a decrease in the degree of crystallinity and hydrogen sorption coefficient, in agreement with several literature references.

Explainable artificial intelligence for microbiome data analysis in colorectal cancer biomarker identification.

Background: Colorectal cancer (CRC) is a type of tumor caused by the uncontrolled growth of cells in the mucosa lining the last part of the intestine. Emerging evidence underscores an association between CRC and gut microbiome dysbiosis. The high mortality rate of this cancer has made it necessary to develop new early diagnostic methods. Machine learning (ML) techniques can represent a solution to evaluate the interaction between intestinal microbiota and host physiology. Through explained artificial intelligence (XAI) it is possible to evaluate the individual contributions of microbial taxonomic markers for each subject. Our work also implements the Shapley Method Additive Explanations (SHAP) algorithm to identify for each subject which parameters are important in the context of CRC. Results: The proposed study aimed to implement an explainable artificial intelligence framework using both gut microbiota data and demographic information from subjects to classify a cohort of control subjects from those with CRC. Our analysis revealed an association between gut microbiota and this disease. We compared three machine learning algorithms, and the Random Forest (RF) algorithm emerged as the best classifier, with a precision of 0.729 ± 0.038 and an area under the Precision-Recall curve of 0.668 ± 0.016. Additionally, SHAP analysis highlighted the most crucial variables in the model's decision-making, facilitating the identification of specific bacteria linked to CRC. Our results confirmed the role of certain bacteria, such as Fusobacterium, Peptostreptococcus, and Parvimonas, whose abundance appears notably associated with the disease, as well as bacteria whose presence is linked to a non-diseased state. Discussion: These findings emphasizes the potential of leveraging gut microbiota data within an explainable AI framework for CRC classification. The significant association observed aligns with existing knowledge. The precision exhibited by the RF algorithm reinforces its suitability for such classification tasks. The SHAP analysis not only enhanced interpretability but identified specific bacteria crucial in CRC determination. This approach opens avenues for targeted interventions based on microbial signatures. Further exploration is warranted to deepen our understanding of the intricate interplay between microbiota and health, providing insights for refined diagnostic and therapeutic strategies.

Nutritional and Physiological Properties of Thymbra spicata: In Vitro Study Using Fecal Fermentation and Intestinal Integrity Models.

(Poly)phenolic-rich Mediterranean plants such as Thymbra spicata have been associated with several health-promoting effects. The nutritional value, as well as physiological interaction of T. spicata with the gastrointestinal tract, has not been investigated before. The nutritional composition of T. spicata leaves was here characterized by standard analytical methods. T. spicata leaves were subjected to ethanolic extraction, simulated gastrointestinal digestion, and anaerobic microbial gut fermentation. Phenols/flavonoid contents and radical scavenging activity were assessed by colorimetric methods. The volatile organic compounds (VOCs) were detected by gas chromatography coupled with mass spectrometry. The effect on intestinal integrity was evaluated using a Caco-2 monolayers mounted in a Ussing chamber. T. spicata contains a high amount of fiber (12.3%) and unsaturated fatty acids (76% of total fat). A positive change in VOCs including short-chain fatty acids was observed without significant change in viable microbe. T. spicata and carvacrol (main phenolic compound) enhanced ionic currents in a concentration-dependent manner without compromising the Caco-2 monolayer's integrity. These effects were partially lost upon simulated digestion and completely abolished after colonic fermentation in line with polyphenols and carvacrol content. Conclusion: T. spicata represents a promising nutrient for the modulation of gut microbiota and the gut barrier. Further studies must better define its mechanisms of action.

Unraveling the microbiome-metabolome nexus: a comprehensive study protocol for personalized management of Behçet's disease using explainable artificial intelligence.

The presented study protocol outlines a comprehensive investigation into the interplay among the human microbiota, volatilome, and disease biomarkers, with a specific focus on Behçet's disease (BD) using methods based on explainable artificial intelligence. The protocol is structured in three phases. During the initial three-month clinical study, participants will be divided into control and experimental groups. The experimental groups will receive a soluble fiber-based dietary supplement alongside standard therapy. Data collection will encompass oral and fecal microbiota, breath samples, clinical characteristics, laboratory parameters, and dietary habits. The subsequent biological data analysis will involve gas chromatography, mass spectrometry, and metagenetic analysis to examine the volatilome and microbiota composition of salivary and fecal samples. Additionally, chemical characterization of breath samples will be performed. The third phase introduces Explainable Artificial Intelligence (XAI) for the analysis of the collected data. This novel approach aims to evaluate eubiosis and dysbiosis conditions, identify markers associated with BD, dietary habits, and the supplement. Primary objectives include establishing correlations between microbiota, volatilome, phenotypic BD characteristics, and identifying patient groups with shared features. The study aims to identify taxonomic units and metabolic markers predicting clinical outcomes, assess the supplement's impact, and investigate the relationship between dietary habits and patient outcomes. This protocol contributes to understanding the microbiome's role in health and disease and pioneers an XAI-driven approach for personalized BD management. With 70 recruited BD patients, XAI algorithms will analyze multi-modal clinical data, potentially revolutionizing BD management and paving the way for improved patient outcomes.

Effects of low-sodium bread on dietary compliance and fecal cultivable bacteria in a randomized controlled pilot trial in hypertensive subjects.

High salt intake and compliance to low-sodium (LS) diets are critical in hypertension. Salt reduction in processed foods can help to achieve the target sodium intake. To verify the hypothesis that an innovative LS formulation of a traditional bread could result in a reduction of sodium intake and blood pressure, we performed a 6-month randomized controlled pilot trial on hypertensive patients. We additionally explored the effects of sodium restriction on blood pressure and fecal cultivable bacteria.Fifty-seven patients were randomized in three groups. Group A (n = 19) followed a free diet using standard bread (750 mg Na/100 g), group B (n = 18) followed a LS diet (2300 mg Na/die) using standard bread, group C (n = 20) followed a LS diet (2300 mg Na/die) using LS bread (280 mg Na/100 g). We measured 24-h urinary sodium, blood pressure, routine parameters, fecal microbial counts (26 patients).After 6 months, as compared to group A, group C showed a reduction of 24-h urinary sodium excretion (-908 mg/24 h), diastolic pressure (-9 mmHg) and microbial counts of Bacteroides, Porphyromonas, Prevotella, Enterobacteriaceae, Staphylococcus, Micrococcus. These results suggest that LS bread could increase the adherence to a LS diet, reducing sodium excretion, diastolic pressure and abundance of some fecal cultivable bacteria.Trial registration Registration nr. NCT03127553, on 25/04/2017.

Maternal Exposure to Endocrine-Disrupting Chemicals: Analysis of Their Impact on Infant Gut Microbiota Composition.

Endocrine disruptors (EDCs) are chemicals that interfere with the endocrine system. EDC exposure may contribute to the development of obesity, type 2 diabetes, and cardiovascular diseases by impacting the composition of an infant's gut microbiota during the first 1000 days of life. To explore the relationship between maternal urinary levels of Bisphenol-A and phthalates (UHPLC-MS/MS), and the composition of the infant gut microbiota (16S rDNA) at age 12 months (T3) and, retrospectively, at birth (T0), 1 month (T1), and 6 months (T2), stool samples from 20 infants breastfed at least once a day were analyzed. Metataxonomic bacteria relative abundances were correlated with EDC values. Based on median Bisphenol-A levels, infants were assigned to the over-exposed group (O, n = 8) and the low-exposed group (B, n = 12). The B-group exhibited higher gut colonization of the Ruminococcus torques group genus and the O-group showed higher abundances of Erysipelatoclostridium and Bifidobacterium breve. Additionally, infants were stratified as high-risk (HR, n = 12) or low-risk (LR, n = 8) exposure to phthalates, based on the presence of at least three phthalates with concentrations exceeding the cohort median values; no differences were observed in gut microbiota composition. A retrospective analysis of gut microbiota (T0-T2) revealed a disparity in ß-diversity between the O-group and the B-group. Considering T0-T3, the Linear Discriminant Effect Size indicated differences in certain microbes between the O-group vs. the B-group and the HR-group vs. the LR-group. Our findings support the potential role of microbial communities as biomarkers for high EDC exposure levels. Nevertheless, further investigations are required to deeply investigate this issue.

Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs): A Scoping Review of 511 Cases, Including 2 New Cases.

Uterine Tumors Resembling Ovarian Sex Cord Tumors (UTROSCTs) are rare uterine mesenchymal neoplasms with uncertain biological potential. These tumors, which affect both premenopausal and postmenopausal women, usually have a benign clinical course. Nevertheless, local recurrences and distant metastases have been described. By analyzing 511 cases retrieved from individual reports and cases series, we provide here the most comprehensive overview of UTROSCT cases available in the literature, supplemented by two new cases of UTROSCTs. Case 1 was an asymptomatic 31-year-old woman who underwent a laparoscopic resection of a presumed leiomyoma. Case 2 was a 58-year-old postmenopausal woman with abnormal vaginal bleeding who underwent an outpatient hysteroscopic biopsy of a suspicious endometrial area. In both cases, immunohistochemical positivity for Calretinin and Inhibin was noted, typical for a sex cord differentiation. In both cases, total laparoscopic hysterectomy with bilateral salpingo-oophorectomy was performed. In light of the available literature, no pathognomonic clinical or imaging finding can be attributed to UTROSCT. Patients usually present with abnormal uterine bleeding or pelvic discomfort, but 20% of them are asymptomatic. In most cases, a simple hysterectomy appears to be the appropriate treatment, but for women who wish to become pregnant, uterus-preserving approaches should be discussed after excluding risk factors. Age, tumor size, lymphovascular space invasion, nuclear atypia, and cervical involvement are not reliable prognostic factors in UTROSCT. The current research suggests that aggressive cases (with extrauterine spread or recurrence) can be identified based on a distinct genetic and immunohistochemical phenotype. For instance, UTROSCTs characterized by GREB1::NCOA1-3 fusions and PD-L1 molecule expression appear to be predisposed to more aggressive behaviors and recurrence, with GREB1::NCOA2 being the most common gene fusion in recurrent tumors. Hence, redefining the criteria for UTROSCTs may allow a better selection of women suitable for fertility-sparing treatments or requiring more aggressive treatments in the future.

Does Alexis Wound Protector/Retractor Reduce the Risk of Surgical Site Infections After Open Radical Cystectomy for Bladder Cancer? Results From a Single Center, Comparative Study.

OBJECTIVE: To assess if Alexis dual-ring wound protector/retractor reduced the incidence of superficial and deep incisional infection following open radical cystectomy (ORC). METHODS: Since January 2020, all procedures were performed using the Alexis retractor. We retrospectively reviewed our ORC database and compared patients who were operated on with Alexis with the same number of consecutive patients operated with a stainless steel retractor in the previous period. Data are presented as median and (interquartile range). RESULTS: Seventy-four patients underwent RC with Alexis (group 1) and 74 with stainless steel retractor (group 2). Median age was 73.0(13) in group 1, 73.5(14) in group 2 (P = .338). There were 59(79.7%) men in both groups. The groups were comparable in terms of comorbidities, body mass index, American Society of Anesthesiology score, and neoadjuvant chemotherapy rate. There was no statistically significant difference in type of lymph node dissection and urinary diversion, total surgical time. Postoperative stay was shorter in group 1 [8(4) days vs 9(4) in group 2, P = .012]. Group 2 had a significantly higher rate of both superficial (8.1% vs 18.9%, P = .045) and deep incisional infection (2.7% vs 14.9%, P = .009). At multivariable analysis, body mass index (OR 1.129 95% CI 1.162-1.283, P = .043) was significantly associated with higher odds of superficial incisional infection. The use of Alexis was significantly associated with lower odds of having both superficial (OR 0.274 95%CI 0.033-0.781, P = .023) and deep incisional infection (OR 0.159 95% CI 0.034-0.745, P = .020). CONCLUSION: The use of Alexis significantly reduces the rate of superficial and deep incisional infection following ORC.

Uterine cervical stenosis: from classification to advances in management. Overcoming the obstacles to access the uterine cavity.

BACKGROUND: To date hysteroscopy is the gold standard technique for the evaluation and management of intrauterine pathologies. The cervical canal represents the access route to the uterine cavity. The presence of cervical stenosis often makes entry into the uterine cavity difficult and occasionally impossible. Cervical stenosis has a multifactorial etiology. It is the result of adhesion processes that can lead to the narrowing or total obliteration of the cervical canal. PURPOSE: In this review, we summarize the scientific evidence about cervical stenosis, aiming to identify the best strategy to overcome this challenging condition. METHODS: The literature review followed the scale for the quality assessment of narrative review articles (SANRA). All articles describing the hysteroscopic management of cervical stenosis were considered eligible. Only original papers that reported data on the topic were included. RESULTS: Various strategies have been proposed to address cervical stenosis, including surgical and non-surgical methods. Medical treatments such as the preprocedural use of cervical-ripening agents or osmotic dilators have been explored. Surgical options include the use of cervical dilators and hysteroscopic treatments. CONCLUSIONS: Cervical stenosis can present challenges in achieving successful intrauterine procedures. Operative hysteroscopy has been shown to have the highest success rate, particularly in cases of severe cervical stenosis, and is currently considered the gold standard for managing this condition. Despite the availability of miniaturized instruments that have made the management of cervical stenosis more feasible, it remains a complex task, even for experienced hysteroscopists.

Microbiome preterm birth DREAM challenge: Crowdsourcing machine learning approaches to advance preterm birth research.

Every year, 11% of infants are born preterm with significant health consequences, with the vaginal microbiome a risk factor for preterm birth. We crowdsource models to predict (1) preterm birth (PTB; <37 weeks) or (2) early preterm birth (ePTB; <32 weeks) from 9 vaginal microbiome studies representing 3,578 samples from 1,268 pregnant individuals, aggregated from public raw data via phylogenetic harmonization. The predictive models are validated on two independent unpublished datasets representing 331 samples from 148 pregnant individuals. The top-performing models (among 148 and 121 submissions from 318 teams) achieve area under the receiver operator characteristic (AUROC) curve scores of 0.69 and 0.87 predicting PTB and ePTB, respectively. Alpha diversity, VALENCIA community state types, and composition are important features in the top-performing models, most of which are tree-based methods. This work is a model for translation of microbiome data into clinically relevant predictive models and to better understand preterm birth.

Metabolomic Profiling of Obese Patients with Altered Intestinal Permeability Undergoing a Very Low-Calorie Ketogenic Diet.

A healthy intestinal permeability facilitates the selective transport of nutrients, metabolites, water, and bacterial products, involving cellular, neural, hormonal, and immune factors. An altered intestinal permeability indicates pathologic phenotypes and is associated with the exacerbation of obesity and related comorbidities. To investigate the impact of altered permeability in obese patients undergoing a calorie-restrictive dietary regimen (VLCKD), we collected urinary and fecal samples from obese patients with both normal and altered permeability (determined based on the lactulose/mannitol ratio) before and after treatment. The analysis of volatile organic compounds (VOCs) aids in understanding the metabolites produced by the intestinal microbiota in this unique ecological niche. Furthermore, we examined clinical and anthropometric variables from the cohort and compared them to significant VOC panels. Consequently, we identified specific markers in the metabolomics data that differentiated between normal and altered profiles before and after the diet. These markers indicated how the variable contribution specifically accounted for interleukins and lipopolysaccharides (LPS). The targeted metabolomics experiment detected no differences in measured short-chain fatty acids (SCFA). In summary, our study evaluated metabolomic markers capable of distinguishing low-grade inflammation conditions, exacerbated in more advanced stages of obesity with altered intestinal permeability.

In silico screening of nanoporous materials for urea removal in hemodialysis applications.

The design of miniaturized hemodialysis devices, such as wearable artificial kidneys, requires regeneration of the dialysate stream to remove uremic toxins from water. Adsorption has the potential to capture such molecules, but conventional adsorbents have low urea/water selectivity. In this work, we performed a comprehensive computational study of 560 porous crystalline adsorbents comprising mainly covalent organic frameworks (COFs), as well as some siliceous zeolites, metal organic frameworks (MOFs) and graphitic materials. An initial screening using Widom insertion method assessed the excess chemical potential at infinite dilution for water and urea at 310 K, providing information on the strength and selectivity of urea adsorption. From such analysis it was observed that urea adsorption and urea/water selectivity increased strongly with fluorine content in COFs, while other compositional or structural parameters did not correlate with material performance. Two COFs, namely COF-F6 and Tf-DHzDPr were explored further through Molecular Dynamics simulations. The results agree with those of the Widom method and allow to identify the urea binding sites, the contribution of electrostatic and van der Waals interactions, and the position of preferential urea-urea and urea-framework interactions. This study paves the way for a well-informed experimental campaign and accelerates the development of novel sorbents for urea removal, ultimately advancing on the path to achieve wearable artificial kidneys.

Diode laser use in hysteroscopic surgery: current status and future perspectives.

Recent advances in surgical technology and innovative techniques have revolutionized surgical gynecology, including transcervical hysteroscopic procedures. Surgical lasers (Nd-Yag, Argon, diode, and CO2 lasers) have been promoted to remove a variety of gynecological pathologies. For hysteroscopic surgery, the diode laser represents the most versatile and feasible innovation, with simultaneous cut and coagulate action, providing improved hemostasis compared with CO2 laser. The newest diode laser devices exhibit increased power and a dual wavelength, to work precisely with reduced thermal dispersion and minimal damage to surrounding tissues. Their efficacy and safety have been validated both in the hospitals as well as in the office setting. Updated evidence reports that several hysteroscopic procedures, including endometrial polypectomies, myomectomies and metroplasties can be successfully performed with a diode laser. Therefore, this review aimed to give a deeper understanding of the role of laser energy in gynecology and subsequently in hysteroscopy in order to safely incorporate this technology into clinical practice.

Simple lattice model explains equilibrium separation phenomena in glassy polymers.

The Robeson bound is a theoretical limit that applies to kinetics-driven membrane separations of gas mixtures. However, this bound does not apply to sorption-driven membrane processes such as CO2/N2 separation, which lacks a theoretical explanation. As a result, we are uncertain about the factors that control the limiting behavior of sorption-driven separations. To address this issue, we employed a simple lattice model and dynamic mean field theory to examine the transport properties of disordered model structures, isolating sorption effects from purely kinetic effects. Our findings indicate that transport effects play a crucial role in sorption-driven processes, and perm-selectivity is consistently lower than sorption selectivity, which is an unattainable limit. We used basic geometric fragments of the structure to explain how transport effects emerge and manifest themselves in sorption-driven processes.

In vivo evaluation of an innovative synbiotics on stage IIIb-IV chronic kidney disease patients.

Background: Microbiota unbalance has been proven to affect chronic kidney disease (CKD) patients and, noteworthy, microbiota composition and activity are implicated in CKD worsening. The progression of kidney failure implies an exceeding accumulation of waste compounds deriving from the nitrogenous metabolism in the intestinal milieu. Therefore, in the presence of an altered intestinal permeability, gut-derived uremic toxins, i.e., indoxyl sulfate (IS) and p-cresyl sulfate (PCS), can accumulate in the blood. Methods: In a scenario facing the nutritional management as adjuvant therapy, the present study assessed the effectiveness of an innovative synbiotics for its ability to modulate the patient gut microbiota and metabolome by setting a randomized, single-blind, placebo-controlled, pilot trial accounting for IIIb-IV stage CKD patients and healthy controls. Metataxonomic fecal microbiota and fecal volatilome were analyzed at the run-in, after 2 months of treatment, and after 1 month of wash out. Results: Significant changes in microbiota profile, as well as an increase of the saccharolytic metabolism, in feces were found for those CKD patients that were allocated in the synbiotics arm. Conclusions: Noteworthy, the here analyzed data emphasized a selective efficacy of the present synbiotics on a stage IIIb-IV CKD patients. Nonetheless, a further validation of this trial accounting for an increased patient number should be considered. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT03815786.