Cancer has the highest death rates due to increased immuno-oncological (IO) challenges and chemoresistance caused by gut dysbiosis, whereas administration of probiotics may reverse these responses against anticancer therapies. Recently, immunotherapeutics have extensively been focused for significant advancements in pharmacological drug discovery and clinical outcomes. Mammals have intestinal epithelial cells, mucosal immune cells, and indigenous gut microbiota which may reshape immunotherapeutics efficacy. These include use of T-cell immune checkpoint inhibitors (ICPI), genetically engineered T-cells, tumor vaccines, monoclonal antibodies (mAbs), and anti-B- and T-cell antibodies. Immunotherapeutics for cancer treatment became popular in both veterinary and human health care systems due to their strong inhibitory actions against PD-1 and CTLA-4 to check tumorigenesis. IO issues in animals also need special attention, where caninized mAbs targeting CD-20 and CD-52 have been clinically used in treating canine B-cell and T-cell lymphomas, respectively. Probiotics appeared as strong immunotherapeutics that might be shaping the epigenetics of the organisms specifically in animal breeding practices for desired features, but limited literature regarding the immunomodulatory effects in humans and animals is available. In addition, considering the important role of probiotics in humans and veterinary medicine, a new perspective on the probiotic-mediated modulation of ncRNAs (miRNAs, lncRNAs, circRNAs) is also highlighted and would be a new therapeutic tool. This review provides insight into the cellular processes and pharmacological activities for treating veterinary infectious diseases and covers small drug molecules as ncRNA-modulators in veterinary medicine.

Nutritional supplements (NS) can help patients by providing various nutrients such as essential vitamins and minerals, helping to prevent and recover from diseases. This study provides a broad overview of the field of NS for sick people through bibliometrics and visualization analysis, to analyze the status and development dynamics, explore the popular research questions and directions, and reveal the development trends and research frontiers.

We searched the Web of Science Core Collection databases for literature related to NS for diseased populations from 2000 to 2024. A total of 1,550 articles were included in the analysis after screening. Analyses performed using CiteSpace and VOSviewer software.

The field of NS for the sick population has witnessed an overall rapid growth in the number of publications, which is divided into three phases: 2000-2008 was the exploratory phase, 2009-2017 was the sustained development phase, and 2018 to date is in the rapid development phase. Research focuses on dietary supplementation, oxidative stress, in vitro injections, development, antioxidant activity, double-blind trials, lipid supplements, functional foods, the health of diseased populations, and the risks of NS.

Different supplements each possess unique benefits and should be chosen according to the type of disease to ensure they contain the corresponding nutrients. Vitamin supplements are widely mentioned among patient populations across the globe. Future trends may focus on applying nutritional supplements in gut microbiota and bioactive compounds. Researchers frequently mention the application of NS in women, infants, and children. It should continue to be monitored and optimized in the future to enhance its therapeutic effects, thereby accelerating patients' recovery and improving their quality of life.

The gut-kidney axis represents the complex interactions between the gut microbiota and kidney, which significantly impact the progression of chronic kidney disease (CKD) and overall patient health. In CKD patients, imbalances in the gut microbiota promote the production of uremic toxins, such as indoxyl sulfate and p-cresyl sulfate, which impair renal function and contribute to systemic inflammation. Mechanisms like endotoxemia, immune activation and oxidative stress worsen renal damage by activating pro-inflammatory and oxidative pathways. Insights into these mechanisms highlight the impact of gut-derived metabolites, bacterial translocation, and immune response changes on kidney health, suggesting new potential approaches for CKD treatment. Clinical applications, such as dietary interventions, prebiotics, probiotics and fecal microbiota transplantation, are promising in adjusting the gut microbiota to alleviate CKD symptoms and slow disease progression. Current research highlights the clinical relevance of the gut-kidney axis, but further study is essential to clarify these mechanisms' diagnostic biomarkers and optimize therapeutic interventions. This review emphasizes the importance of an integrated approach to CKD management, focusing on the gut microbiota as a therapeutic target to limit kidney injury.

Peritoneal dialysis (PD) is a commonly used modality for kidney replacement therapy for patients with end-stage kidney disease (ESKD). PD offers many benefits, including home-based care, greater flexibility, and preservation of residual kidney function compared to in-center hemodialysis. Nonetheless, patients undergoing PD often face significant challenges, including systemic inflammation, PD-related peritonitis, metabolic disorders, and cardiovascular issues that can negatively affect their quality of life and treatment outcomes. Recent studies have demonstrated the crucial role of the gut microbiome in overall health and treatment results, supporting the hypothesis that probiotics may bring potential benefits to the general population of ESKD patients. However, specific data on probiotic use in PD patients are limited. This opinion review aims to summarize the current knowledge on the relationship between PD and the gut microbiome and offers a novel perspective by specifically exploring how probiotic interventions could improve the outcomes of PD treatment. The review also outlines some clinical data supporting the effectiveness of probiotics in patients undergoing PD and considers the difficulties and restrictions in their application. Based on the current knowledge gaps, this study seeks to explore future research directions and their implications for clinical practice.

Vascular calcification (VC) is a common complication in patients with chronic kidney disease (CKD) and a major risk factor for increased cardiovascular mortality in patients with CKD. Its pathology and pathogenesis are complex and have not been fully elucidated. Trimethylamine N-oxide (TMAO) is an enteric-borne uremic toxin that has been found to play a role in the progression of VC. This article mainly reviews the metabolism of TMAO, the relationship between TMAO and VC in CKD patients, and possible treatments for TMAO, aiming to further explore the mechanism of VC occurrence in CKD patients and provide potential diagnostic and treatment strategies.

Evidence suggests that Lactiplantibacillus plantarum (LP) can positively influence gut microbiota, subsequently affecting brain function via the gut-brain axis. However, the oral administration of LP may subject it to damage from gastric acid. To address this issue, a microencapsulation system was developed to protect LP and enhance its viability in the gastrointestinal tract. In the study, zein-microencapsulated LP (MLP) was prepared using the phase separation method. We found that the optimal conditions to encapsulate LP (9 log CFU/mL) were a zein concentration of 10 mg/mL and a zein-to-bacteria mass ratio of 5:1. Scanning electron microscopy and dynamic light scattering analysis demonstrated that MLP exhibited a microstructure with an approximate diameter of 4 µm. Findings also revealed that microencapsulation markedly improved the in vitro survival rate of LP compared to free cells and allowed for controlled release. Subsequent in vivo studies in mice showed that this encapsulation not only boosted the colonization of LP but also ameliorated the imbalance of gut microbiota associated with depression. An analysis of the intestinal microbiota in mice identified 13 genera that exhibited significant shifts in abundance due to the depressive states. The administration of MLP reversed these microbial changes, underscoring its therapeutic potential. Additionally, the study examined the expression of pro-inflammatory cytokines. The administrated MLP was found to reverse the inflammation in both the intestine and hippocampus of mice with depression. Behavioral assessments in mouse models corroborated the efficacy of MLP in preventing depression, positioning it as a promising daily supplement.

Dyslipidemia is a common metabolic complication in patients undergoing peritoneal dialysis (PD) and has traditionally been viewed primarily in terms of cardiovascular risk. Current guidelines do not recommend initiating lipid-lowering therapy in dialysis patients due to insufficient evidence of its benefits on cardiovascular mortality. However, the impact of dyslipidemia in PD patients may extend beyond cardiovascular concerns, influencing PD-related outcomes such as the peritoneal ultrafiltration rate, residual kidney function, PD technique survival, and overall mortality. This review challenges the traditional perspective by discussing dyslipidemia's potential role in PD-related complications, which may account for the observed link between dyslipidemia and increased all-cause mortality in PD patients. It explores the pathophysiology of dyslipidemia in PD, the molecular mechanisms linking dyslipidemia to peritoneal membrane dysfunction, and summarizes clinical evidence supporting this hypothesis. In addition, this paper examines the potential for therapeutic strategies to manage dyslipidemia to improve peritoneal membrane function and patient outcomes. The review calls for future research to investigate dyslipidemia as a potential contributor to peritoneal membrane dysfunction and to develop targeted interventions for PD patients.

The relationship between gut microbiota and osteoarthritis (OA) occurrence remains unclear. Existing research needs to clearly understand how basal metabolic rate (BMR) regulates this relationship. Therefore, using a two-step bidirectional Mendelian Randomization approach, our study aims to investigate whether BMR levels mediate the causal relationship between gut microbiota and OA.

In this study, we examined publicly available summary statistics from Genome-Wide Association Studies (GWAS) to determine the correlation between gut microbiota and OA. The analysis included one primary dataset and two secondary datasets. Initially, a two-step, two-sample, and reverse MR analysis was performed to identify the causal relationship between gut microbiota and OA. Subsequently, a two-step MR analysis revealed that the relationship between microbiota and OA is mediated by BMR. Sensitivity analyses confirmed the robustness of the study results.

In our analysis of the primary dataset, we discovered a positive correlation between three taxa and the outcome of OA, and eight taxa exhibited a negative correlation with the OA outcome. Through comparisons with the secondary dataset and multiple testing corrections, we found a negative association between the class Actinobacteria (OR=0.992886277, p-value = 0.003) and the likelihood of OA occurrence. Notably, knee osteoarthritis (KOA) and hip osteoarthritis (HOA) had a strong negative correlation (OR = 0.927237553/0.892581219). Our analysis suggests that BMR significantly mediates the causal pathway from Actinobacteria to OA, with a mediated effect of 2.59%. Additionally, BMR mediates 3.98% of the impact in the path from the order Bifidobacteriales and the family Bifidobacteriaceae to OA. Besides these findings, our reverse analysis did not indicate any significant effect of OA on gut microbiota or BMR.

Our research results indicate that an increase in the abundance of specific gut microbial taxa is associated with a reduced incidence of OA, and BMR levels mediate this causal relationship. Further large-scale randomized controlled trials are necessary to validate the causal impact of gut microbiota on the risk of OA. This study provides new insights into the potential prevention of OA by modulating the gut microbiota.

Chronic kidney disease (CKD) is a very prevalent and insidious disease, particularly with initially poorly manifested symptoms that progressively culminate in the manifestation of an advanced stage of the condition. The gradual impairment of kidney function, particularly decreased filtration capacity, results in the retention of uremic toxins and affects numerous molecular mechanisms within the body. The dysbiotic intestinal microbiome plays a crucial role in the accumulation of protein-bound uremic toxins such as p-cresol (pC), indoxyl sulfate (IS), and p-cresyl sulfate (p-CS) through the ongoing fermentation process. The described phenomenon leads to an elevated level of oxidative stress and inflammation, subsequently resulting in tissue damage and complications, particularly an increase in cardiovascular risk, representing the predominant cause of mortality in chronic kidney disease (CKD). Therefore, exploring methods to reduce uremic toxins is currently a pivotal therapeutic strategy aimed at reducing the risk of organ damage in patients with chronic kidney disease (CKD). This review aims to summarize recent discoveries on modifying the composition of the intestinal microbiota through the introduction of special probiotic and synbiotic supplements for CKD therapy. The potential to connect the gut microbiota with CKD opens the possibility for further extensive research in this area, which could lead to the incorporation of synbiotics and probiotics into the fundamental treatment and prevention of CKD.

The human gut microbiota constitutes a complex community of microorganisms residing within the gastrointestinal tract, encompassing a vast array of species that play crucial roles in health and disease. The disease processes involved in chronic kidney disease (CKD) and end-stage kidney disease (ESKD) are now increasingly established to result in dysregulation of gut microbiota composition and function. Gut microbiota dysbiosis has been associated with poor clinical outcomes and all-cause mortality in patients with ESKD, particularly individuals receiving dialysis. Prior studies highlighted various factors that affect gut microbiota dysbiosis in CKD and ESKD. These include, but are not limited to, uraemic toxin accumulation, chronic inflammation, immune dysfunction, medications, and dietary restrictions and nutritional status. There is a lack of studies at present that focus on the evaluation of gut microbiota dysbiosis in the context of dialysis. Knowledge on gut microbiota changes in this context is important for determining their impact on dialysis-specific and overall outcomes for this patient cohort. More importantly, evaluating gut microbiota composition can provide information into potential targets for therapeutic intervention. Identification of specific microbial signatures may result in further development of personalised treatments to improve patient outcomes and mitigate complications during dialysis. Optimising gut microbiota through various therapeutic approaches, including dietary adjustments, probiotics, prebiotics, medications, and faecal transplantation, have previously demonstrated potential in multiple medical conditions. It remains to be seen whether these therapeutic approaches are effective within the dialysis setting. Our review aims to evaluate evidence relating to alterations in the gut microbiota of patients undergoing dialysis. A growing body of evidence pointing to the complex yet significant relationship which surrounds gut microbiota and kidney health emphasises the importance of gut microbial balance to improve outcomes for individuals receiving dialysis.

Chronic kidney disease (CKD) affects 9.1% of the population worldwide. CKD may lead to structural and functional gastrointestinal alterations, including impairment in the intestinal barrier, digestion and absorption of nutrients, motility, and changes to the gut microbiome. These changes can lead to increased gastrointestinal symptoms in people with CKD, even in early grades of kidney dysfunction. Gastrointestinal symptoms have been associated with lower quality of life and reduced nutritional status. Therefore, there has been considerable interest in improving gastrointestinal health in this clinical population. Gastrointestinal health can be influenced by lifestyle and medications, particularly in advanced grades of kidney dysfunction. Therapies focused on gastrointestinal health have been studied, including the use of probiotics, prebiotics, and synbiotics, yielding limited and conflicting results. This review summarizes the alterations in the gastrointestinal tract structure and function and provides an overview of potential nutritional interventions that kidney disease professionals can provide to improve gastrointestinal health in individuals with CKD.

The most common kidney replacement therapy (KRT) worldwide is hemodialysis (HD), and only 5%-10% of patients are prescribed peritoneal dialysis (PD) as KRT. Despite PD being a different method, these patients also present particular complications, such as oxidative stress, gut dysbiosis, premature aging, and mitochondrial dysfunction, leading to an inflammation process and high cardiovascular mortality risk. Although recent studies have reported nutritional strategies in patients undergoing HD with attempts to mitigate these complications, more information must be needed for PD patients. Therefore, this review provides a comprehensive analysis of recent studies of nutritional intervention to mitigate inflammation in PD patients.

To ensure effective administration of probiotics in clinical practice, it is crucial to comprehend the specific strains and their association with human health. Therefore, we conducted a systematic review and meta-analysis to evaluate the scientific evidence on the impact of Lactiplantibacillus plantarum probiotic consumption on human health. Out of 11,831 records, 135 studies were assessed qualitatively, and 18 studies were included in the meta-analysis. This systematic review demonstrated that probiotic supplementation with L. plantarum, either alone or in combination, can significantly improve outcomes for patients with specific medical conditions. Meta-analysis revealed notable benefits in periodontal health, evidenced by reduced pocket depth and bleeding on probing (p < 0.001); in gastroenterological health, marked by significant reductions in abdominal pain (p < 0.001); and in infectious disease, through a reduction in C-reactive protein levels (p < 0.001). Cardiovascular benefits included lowered total cholesterol and low-density lipoprotein cholesterol in the L. plantarum intervention group (p < 0.05). Our study's clinical significance highlights the importance of considering probiotic strain and their application to specific diseases when planning future studies and clinical interventions, emphasizing the need for further research in this area.

Gut dysbiosis contributes to deterioration of chronic kidney disease (CKD). Probiotics are a potential approach to modulate gut microbiota and gut-derived metabolites to alleviate CKD progression. We aim to provide a comprehensive view of CKD-related gut dysbiosis and a critical perspective on probiotic function in CKD. First, this review addresses gut microbial alterations during CKD progression and the adverse effects associated with the changes in gut-derived metabolites. Second, we conduct a thorough examination of the latest clinical trials involving probiotic intervention to unravel critical pathways via the gut-kidney axis. Finally, we propose our viewpoints on limitations, further considerations, and future research prospects of probiotic adjuvant therapy in alleviating CKD progression. Enhancing our understanding of host-microbe interactions is crucial for gaining precise insights into the mechanisms through which probiotics exert their effects and identifying factors that influence the effectiveness of probiotics in developing strategies to optimize their use and enhance clinical outcomes.

Several billion microorganisms reside in the gastrointestinal lumen, including viruses, bacteria, fungi, and yeast. Among them, probiotics were primarily used to cure digestive disorders such as intestinal infections and diarrhea; however, with a paradigm shift towards alleviating health through food, their importance is large. Moreover, recent studies have changed the perspective that probiotics prevent numerous ailments in the major organs. Probiotics primarily produce biologically active compounds targeting discommodious pathogens. This review demonstrates the implications of using probiotics from different genres to prevent and alleviate ailments in the primary human organs. The findings reveal that probiotics immediately activate anti-inflammatory mechanisms by producing anti-inflammatory cytokines such as interleukin (IL)-4, IL-10, IL-11, and IL-13, and hindering pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α by involving regulatory T cells (Tregs) and T helper cells (Th cells). Several strains of Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus casei, Lactobacillus reuteri, Bifidobacterium longum, and Bifidobacterium breve have been listed among the probiotics that are excellent in alleviating various simple to complex ailments. Therefore, the importance of probiotics necessitates robust research to unveil the implications of probiotics, including the potency of strains, the optimal dosages, the combination of probiotics, their habitat in the host, the host response, and other pertinent factors.

Protein energy wasting (PEW) is common in patients on hemodialysis, and its development may involve gut microbial dysbiosis. However, the exact relationship between the composition of different flora and the development of PEW remains unclear.

This is an observational longitudinal study on 115 patients undergoing hemodialysis who were followed up for 1 year. All the patients were evaluated at baseline, and different microbiota compositions were determined. After a 1 year follow-up period, the correlations between clinical parameter variations and the relative abundance of different gut flora were assessed using Spearman correlation. Moreover, the associations of the abundance of different gut microbiota with decrease in lean tissue mass and the development of PEW were analyzed using ROC curve and logistical regression analyses.

We found that the relative abundances of Actinobacteria and Bifidobacteriaceae were significantly lower in patients with PEW than in those who did not develop PEW (p < 0.05). The abundance of Actinobacteria and Bifidobacteriaceae correlated positively with variations in serum albumin levels (r = 0.213, p = 0.035 and r = 0.214, p = 0.034, respectively), lean tissue mass (r = 0.296, p = 0.007 and r = 0.238, p = 0.002, respectively), and lean tissue index (r = 0.377, p < 0.001 and r = 0.419, p < 0.001, respectively). The area under the ROC curve or AUC values of Actinobacteria and Bifidobacteriaceae for the prediction of lean tissue mass decrease ranged from 0.676 to 0.708 (p < 0.05). Thus, decrease in the abundance of Actinobacteria and Bifidobacteriaceae may be associated with decrease in lean tissue mass and the occurrence of PEW.

The present findings imply Actinobacteria and Bifidobacteriaceae may be potential markers for predicting skeletal muscle mass decrease and PEW development in patients on hemodialysis.

The gut microbiome is known as the tenth system of the human body that plays a vital role in the intersection between health and disease. The considerable inter-individual variability in gut microbiota poses both challenges and great prospects in promoting precision medicine in cardiovascular diseases (CVDs). In this review, based on the development, evolution, and influencing factors of gut microbiota in a full life circle, we summarized the recent advances on the characteristic alteration in gut microbiota in CVDs throughout different life stages, and depicted their pathological links in mechanism, as well as the highlight achievements of targeting gut microbiota in CVDs prevention, diagnosis and treatment. Personalized strategies could be tailored according to gut microbiota characteristics in different life stages, including gut microbiota-blood metabolites combined prediction and diagnosis, dietary interventions, lifestyle improvements, probiotic or prebiotic supplements. However, to fulfill the promise of a lifelong cardiovascular health, more mechanism studies should progress from correlation to causality and decipher novel mechanisms linking specific microbes and CVDs. It is also promising to use the burgeoning artificial intelligence and machine learning to target gut microbiota for developing diagnosis system and screening for new therapeutic interventions.

Increasing evidence suggests that multipotent mesenchymal stem/stromal cells (MSCs) are a promising intervention strategy in treating autoimmune inflammatory diseases. It should be stated that systemic immunoregulation is increasingly recognized among the beneficial effects of MSCs and probiotics in treating morbid autoimmune disorders such as lupus. This study aimed to determine if immunoregulatory probiotics L. rhamnosus or L. delbrueckii can change the immunomodulatory effects of MSCs in lupus-like disease.

Pristane-induced lupus (PIL) mice model was created via intraperitoneal injection of Pristane and then confirmed. Naïve MSCs (N-MSCs) were coincubated with two Lactobacillus strains, rhamnosus (R-MSCs) or delbrueckii (D-MSCs), and/or a combination of both (DR-MSCs) for 48 h, then administrated intravenously in separate groups. Negative (PBS-treated normal mice) and positive control groups (PBS-treated lupus mice) were also investigated. At the end of the study, flow cytometry and enzyme-linked immunosorbent assay (ELISA) analysis were used to determine the percentage of Th cell subpopulations in splenocytes and the level of their master cytokines in sera, respectively. Moreover, lupus nephritis was investigated and compared. Analysis of variance (ANOVA) was used for multiple comparisons.

Abnormalities in serum levels of anti-dsDNA antibodies, creatinine, and urine proteinuria were significantly suppressed by MSCs transplantation, whereas engrafted MSCs coincubation with both L. strains did a lesser effect on anti-dsDNA antibodies. L. rhamnosus significantly escalated the ability of MSCs to scale down the inflammatory cytokines (IFN-ɣ, IL-17), while L. delbrueckii significantly elevated the capacity of MSCs to scale down the percentage of Th cell subpopulations. However, incubation with both strains induced MSCs with augmented capacity in introducing inflammatory cytokines (IFN-ɣ, IL-17). Strikingly, R-MSCs directly restored the serum level of TGF-β more effectively and showed more significant improvement in disease parameters than N-MSCs. These results suggest that R-MSCs significantly attenuate lupus disease by further skew the immune phenotype of MSCs toward increased immunoregulation.

Results demonstrated that Lactobacillus strains showed different capabilities in training/inducing new abilities in MSCs, in such a way that pretreated MSCs with L. rhamnosus might benefit the treatment of lupus-like symptoms, given their desirable properties.

Growing evidence has demonstrated that patients undergoing peritoneal dialysis (PD) are more likely to experience cognitive impairment than patients with non-dialysis end-stage renal disease (ESRD); however, the underlying mechanisms remain unclear. This study aimed to identify the role and predictive significance of gut microbiome alterations in PD-associated cognitive impairment.

A total of 29 non-dialysis ESRD patients and 28 PD patients were enrolled in this study and divided into subgroups according to the Montreal Cognitive Assessment (MoCA). Faecal samples were analyzed using 16 S rRNA. Mini-Mental State Examination (MMSE) and MoCA scores were used to assess the degree of cognitive impairment in patients.

The 16 S rRNA analysis demonstrated differences in gut microbiome abundance and structure between PD and non-dialysis ESRD patients and between PD patients with cognitive impairment (PCI) and PD patients with normal cognition (PNCI). At family and genus levels, Prevotellaceae exhibited the greatest structure difference, while Lactobacillus exhibited the greatest abundance difference between PCI and PNCI. Altered microbiota abundance significantly correlated with cognitive function and serum indicators in PD. In addition, different modules related to fatty acid, lipid, pantothenate, and coenzyme A biosynthesis, and tyrosine and tryptophan metabolism were inferred from 16 S rRNA data between PCI and PNCI. Both groups could be distinguished using models based on the abundance of Lactobacillaceae (Area under curve [AUC] = 0.83), Actinomycetaceae (AUC = 0.798), and Prevotellaceae (AUC = 0.778) families and Lactobacillus (AUC = 0.848) and Actinomyces (AUC = 0.798) genera.

Gut microbiome evaluation could aid early cognitive impairment diagnosis in patients undergoing PD.

As dysbiosis of gut microbiota is recognized as a major risk factor for malnutrition in hemodialysis (HD) patients, we aimed to assess the effects of fortified synbiotic dessert on malnutrition, oxidative stress, inflammation, and quality of life in patients undergoing hemodialysis. A total of 50 hemodialysis patients were randomized into two groups of intervention and control to consume either 50 g of synbiotic dessert fortified with vitamin D (1000 IU) and calcium (500 mg) (FSD) or 50 g of control dessert (CD) for 8 weeks, respectively. Changes in nutritional status [Subjective Global Assessment (SGA)], anthropometric measures, malondialdehyde (MDA), total antioxidant capacity (TAC), high-sensitivity C-reactive protein (hs-CRP), ferritin, biochemistry [serum albumin, vitamin D, creatinine, blood urea nitrogen (BUN), complete blood count (CBC), and electrolytes], and quality of life were assessed before and at the end of the trial. The SGA scores and serum ferritin levels decreased significantly in the FSD group compared to the control group (p = .01 and p = .03, respectively). Regarding other markers, no statistically significant changes were found comparing the two groups. This novel fortified synbiotic dessert as a functional food may be effective in reducing the severity of malnutrition by improving SGA score in short term in hemodialysis patients. Thus, it is suggested to do further studies to elucidate the possible mechanisms related to the effects of this dessert on microbiota, skeletal muscle mass, and inflammation in HD in long term.

To investigate the efficacy of vaginal probiotics administration in combination with prophylactic antibiotics versus antibiotic prophylaxis only on perinatal outcomes in women with preterm premature rupture of membrane (PPROM).

Four different databases were searched from inception till March 2023. We selected randomized controlled trials (RCTs) that compared vaginal probiotics along with antibiotics versus antibiotics only among pregnant women who were presented with PPROM between 24 and 34 weeks of gestation. We performed the meta-analysis using Revman software. Our primary outcomes were gestational age at birth and latency period duration. Our secondary outcomes were the rate of admission in the neonatal intensive care unit (NICU), infant birth weight, length of stay in the NICU, and neonatal complications.

Four RCTs, involving a total of 339 patients, were included in the meta-analysis. The gestational age at the time of delivery and latency period duration were significantly higher among probiotics + antibiotics group (p = 0.01 & p < 0.001). There was a significant reduction in the rate of NICU admission and length of NICU stay among the probiotics + antibiotics group compared to the antibiotics only group. A significant improvement in the infant birth weight after delivery was demonstrated among the probiotics + antibiotics group (p = 0.002). Although there was a decrease in the incidence of neonatal sepsis and respiratory distress syndrome within probiotics + antibiotics group versus antibiotics only group, these differences were not statistically significant (p > 0.05).

The combination of vaginal probiotics and antibiotic prophylaxis has been shown to effectively improve perinatal outcomes in women with PPROM. Further trials are needed to validate our findings.

Chronic kidney disease (CKD) is a severe condition and a significant public health issue worldwide, carrying the burden of an increased risk of cardiovascular events and mortality. The traditional factors that promote the onset and progression of CKD are cardiometabolic risk factors like hypertension and diabetes, but non-traditional contributors are escalating. Moreover, gut dysbiosis, inflammation, and an impaired immune response are emerging as crucial mechanisms in the disease pathology. The gut microbiome and kidney disease exert a reciprocal influence commonly referred to as "the gut-kidney axis" through the induction of metabolic, immunological, and endocrine alterations. Periodontal diseases are strictly involved in the gut-kidney axis for their impact on the gut microbiota composition and for the metabolic and immunological alterations occurring in and reciprocally affecting both conditions. This review aims to provide an overview of the dynamic biological interconnections between oral health status, gut, and renal pathophysiology, spotlighting the dynamic oral-gut-kidney axis and raising whether periodontal diseases and gut microbiota can be disease modifiers in CKD. By doing so, we try to offer new insights into therapeutic strategies that may enhance the clinical trajectory of CKD patients, ultimately advancing our quest for improved patient outcomes and well-being.

The gut microbiota plays a crucial role in the human microenvironment. Dysbiosis of the gut microbiota is a common pathophysiological phenomenon in critically ill patients. Therefore, utilizing intestinal microbiota to prevent complications and improve the prognosis of critically ill patients is a possible therapeutic direction. The gut microbiome-based therapeutics approach focuses on improving intestinal microbiota homeostasis by modulating its diversity, or treating critical illness by altering the metabolites of intestinal microbiota. There is growing evidence that fecal microbiota transplantation (FMT), selective digestive decontamination (SDD), and microbiota-derived therapies are all effective treatments for critical illness. However, different treatments are appropriate for different conditions, and more evidence is needed to support the selection of optimal gut microbiota-related treatments for different diseases. This narrative review summarizes the curative effects and limitations of microbiome-based therapeutics in different critically ill adult patients, aiming to provide possible directions for gut microbiome-based therapeutics for critically ill patients such as ventilator-associated pneumonia, sepsis, acute respiratory distress syndrome, and COVID-19, etc.

Functional constipation is a common problem in otherwise healthy children. Children with chronic kidney disease (CKD) and on dialysis have additional disease-related risk factors including the uremic milieu, fluid and dietary restrictions, and decreased physical activity, as well as treatment-related risk factors such as dialysis therapy and polypharmacy that contribute to and compound the problem. Constipation causes significant distress for children and their caregivers. In children on peritoneal dialysis, severe constipation can impede catheter function and ultrafiltration. Accumulating evidence points to a possible bidirectional relationship between constipation and CKD, potentially mediated by gut dysbiosis with consequent increased generation of gut-derived uremic toxins and disruption of intestinal epithelium integrity leading to translocation of noxious luminal contents into the circulation inducing systemic inflammation. Effective management of constipation is required but there is little published data on the safety and effectiveness of treatments in adults or children with CKD. In this review, we discuss the diagnosis and epidemiology of functional constipation, provide an overview of its pathophysiology, summarize the therapeutic management, and reflect on the challenges in children with CKD.

The majority of kidney recipients are a subset of chronic kidney disease. Our previous study demonstrated that the combination of Lactobacillus plantarum and Lactobacillus paracasei (Lm) had the highest clearance ability of uremic toxins and improved kidney function in a mouse model. This study aimed to evaluate Lm in improving graft function, effects on immunosuppressants, and safety in transplant recipients.

We retrospectively reviewed 24 patients. Twelve of them take Lm regularly; we compared the creatinine measurements and estimated glomerular filtration rate 3 months before and after Lm using a 2-tailed Wilcoxon matched-pairs signed-rank test while also evaluating the drug level of immunosuppressants and infection events. Other 12 patients who do not have Lm for evaluation of laboratory calibration and compared the proportion of improving creatinine using Fisher's exact test.

The creatinine decreased by 0.06 mg/dL (P = .02), and the estimated glomerular filtration rate increased by 3.1 mL/min/1.73 m2 (P = .03) after Lm supplementation. This pilot study revealed the association of higher incidence (odds ratio 13.3, 95% CI 1.64-77.2, P = .01) of decreasing creatinine in transplant recipients using Lm. Furthermore, results showed a trend of higher trough levels of tacrolimus and sirolimus, which might provide a potential strategy for reducing the dosages of immunosuppressants.

Our findings revealed an association between a higher incidence of decreasing creatinine in kidney transplant recipients using Lm, which may also provide a potential strategy for reducing the acquired dosages of immunosuppressants.

Chronic kidney disease (CKD) is a major public health problem affecting 13% of the global population. Prior research has indicated that CKD is associated with gut dysbiosis. Gut dysbiosis may lead to the development and/or progression of CKD, which in turn may in turn lead to gut dysbiosis as a result of uraemic toxins, intestinal wall oedema, metabolic acidosis, prolonged intestinal transit times, polypharmacy (frequent antibiotic exposures) and dietary restrictions used to treat CKD. Interventions such as synbiotics, prebiotics, and probiotics may improve the balance of the gut flora by altering intestinal pH, improving gut microbiota balance and enhancing gut barrier function (i.e. reducing gut permeability).

This review aimed to evaluate the benefits and harms of synbiotics, prebiotics, and probiotics for people with CKD.

We searched the Cochrane Kidney and Transplant Register of Studies up to 9 October 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov.

We included randomised controlled trials (RCTs) measuring and reporting the effects of synbiotics, prebiotics, or probiotics in any combination and any formulation given to people with CKD (CKD stages 1 to 5, including dialysis and kidney transplant). Two authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria.

Data extraction was independently carried out by two authors using a standard data extraction form. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Forty-five studies (2266 randomised participants) were included in this review. Study participants were adults (two studies in children) with CKD ranging from stages 1 to 5, with patients receiving and not receiving dialysis, of whom half also had diabetes and hypertension. No studies investigated the same synbiotic, prebiotic or probiotic of similar strains, doses, or frequencies. Most studies were judged to be low risk for selection bias, performance bias and reporting bias, unclear risk for detection bias and for control of confounding factors, and high risk for attrition and other biases. Compared to prebiotics, it is uncertain whether synbiotics improve estimated glomerular filtration rate (eGFR) at four weeks (1 study, 34 participants: MD -3.80 mL/min/1.73 m², 95% CI -17.98 to 10.38), indoxyl sulfate at four weeks (1 study, 42 participants: MD 128.30 ng/mL, 95% CI -242.77 to 499.37), change in gastrointestinal (GI) upset (borborymgi) at four weeks (1 study, 34 participants: RR 15.26, 95% CI 0.99 to 236.23), or change in GI upset (Gastrointestinal Symptom Rating Scale) at 12 months (1 study, 56 participants: MD 0.00, 95% CI -0.27 to 0.27), because the certainty of the evidence was very low. Compared to certain strains of prebiotics, it is uncertain whether a different strain of prebiotics improves eGFR at 12 weeks (1 study, 50 participants: MD 0.00 mL/min, 95% CI -1.73 to 1.73), indoxyl sulfate at six weeks (2 studies, 64 participants: MD -0.20 μg/mL, 95% CI -1.01 to 0.61; I² = 0%) or change in any GI upset, intolerance or microbiota composition, because the certainty of the evidence was very low. Compared to certain strains of probiotics, it is uncertain whether a different strain of probiotic improves eGFR at eight weeks (1 study, 30 participants: MD -0.64 mL/min, 95% CI -9.51 to 8.23; very low certainty evidence). Compared to placebo or no treatment, it is uncertain whether synbiotics improve eGFR at six or 12 weeks (2 studies, 98 participants: MD 1.42 mL/min, 95% CI 0.65 to 2.2) or change in any GI upset or intolerance at 12 weeks because the certainty of the evidence was very low. Compared to placebo or no treatment, it is uncertain whether prebiotics improves indoxyl sulfate at eight weeks (2 studies, 75 participants: SMD -0.14 mg/L, 95% CI -0.60 to 0.31; very low certainty evidence) or microbiota composition because the certainty of the evidence is very low. Compared to placebo or no treatment, it is uncertain whether probiotics improve eGFR at eight, 12 or 15 weeks (3 studies, 128 participants: MD 2.73 mL/min, 95% CI -2.28 to 7.75; I² = 78%), proteinuria at 12 or 24 weeks (1 study, 60 participants: MD -15.60 mg/dL, 95% CI -34.30 to 3.10), indoxyl sulfate at 12 or 24 weeks (2 studies, 83 participants: MD -4.42 mg/dL, 95% CI -9.83 to 1.35; I² = 0%), or any change in GI upset or intolerance because the certainty of the evidence was very low. Probiotics may have little or no effect on albuminuria at 12 or 24 weeks compared to placebo or no treatment (4 studies, 193 participants: MD 0.02 g/dL, 95% CI -0.08 to 0.13; I² = 0%; low certainty evidence). For all comparisons, adverse events were poorly reported and were minimal (flatulence, nausea, diarrhoea, abdominal pain) and non-serious, and withdrawals were not related to the study treatment.

We found very few studies that adequately test biotic supplementation as alternative treatments for improving kidney function, GI symptoms, dialysis outcomes, allograft function, patient-reported outcomes, CVD, cancer, reducing uraemic toxins, and adverse effects. We are not certain whether synbiotics, prebiotics, or probiotics are more or less effective compared to one another, antibiotics, or standard care for improving patient outcomes in people with CKD. Adverse events were uncommon and mild.

This study aimed to investigate whether the gastroprotective effects of three types of bacterial levans are correlated with their prebiotic-associated anti-inflammatory/antioxidant potentials. Three levans designated as LevAE, LevP, and LevZ were prepared from bacterial honey isolates; purified, and characterized using TLC, NMR, and FTIR. The anti-inflammatory properties of levan preparations were assessed in LPS-stimulated RAW 264.7 cell lines, while their safety and gastroprotective potentials were assessed in Wistar rats. The three levans significantly reduced ulcer number (22.29-70.05 %) and severity (31.76-80.54 %) in the ethanol-induced gastric ulcer model compared to the control (P < 0.0001/each), with the highest effect observed in LevAE and levZ (200 mg/each) (P < 0.0001). LevZ produced the highest levels of glutathione; catalase activity, and the lowest MDA levels (P = 0.0001/each). The highest anti-inflammatory activity was observed in LevAE and levZ in terms of higher inhibitory effect on IL-1β and TNF-α production (P < 0.0001 each); COX2, PGE2, and NF-κB gene expression. The three levan preparations also proved safe with no signs of toxicity, with anti-lipidemic properties as well as promising prebiotic activity that directly correlated with their antiulcer effect. This novel study highlights the implication of prebiotic-mediated systemic immunomodulation exhibited by bacterial levans that directly correlated with their gastroprotective activity.

Recent observational studies and clinical trials demonstrated an association between gut microbiota and musculoskeletal (MSK) diseases. Nonetheless, whether the gut microbiota composition has a causal effect on the risk of MSK diseases remains unclear.

Based on large-scale genome-wide association studies (GWAS), we performed a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between gut microbiota and six MSK diseases, namely osteoporosis (OP), fracture, sarcopenia, low back pain (LBP), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). Instrumental variables for 211 gut microbiota taxa were obtained from the largest available GWAS meta-analysis (n = 18,340) conducted by the MiBioGen consortium. And the summary-level data for six MSK diseases were derived from published GWAS. The inverse-variance weighted (IVW) method was conducted as a primary analysis to estimate the causal effect, and the robustness of the results was tested via sensitivity analyses using multiple methods. The Bonferroni-corrected test was used to determine the strength of the causal relationship between gut microbiota and various MSK diseases. Finally, a reverse MR analysis was applied to evaluate reverse causality.

According to the IVW method, we found 57 suggestive causal relationships and 3 significant causal relationships between gut microbiota and MSK diseases. Among them, Genus Bifidobacterium (β: 0.035, 95% CI: 0.013-0.058, p = 0.0002) was associated with increased left handgrip strength, Genus Oxalobacter (OR: 1.151, 95% CI: 1.065-1.245, p = 0.0003) was correlated with an increased risk of LBP, and Family Oxalobacteraceae (OR: 0.792, 95% CI: 0.698-0.899, p = 0.0003) was linked with a decreased risk of RA. Subsequently, sensitivity analyses revealed no heterogeneity, directional pleiotropy, or outliers for the causal effect of specific gut microbiota on MSK diseases (p > 0.05). Reverse MR analysis showed fracture may result in a higher abundance of Family Bacteroidales (p = 0.030) and sarcopenia may lead to a higher abundance of Genus Sellimonas (p = 0.032).

Genetic evidence suggested a causal relationship between specific bacteria taxa and six MSK diseases, which highlights the association of the "gut-bone/muscle" axis. Further exploration of the potential microbiota-related mechanisms of bone and muscle metabolism might provide novel insights into the prevention and treatment of MSK diseases.

Uremic toxins are chemicals, organic or inorganic, that accumulate in the body fluids of individuals with acute or chronic kidney disease and impaired renal function. More than 130 uremic solutions are included in the most comprehensive reviews to date by the European Uremic Toxins Work Group, and novel investigations are ongoing to increase this number. Although approaches to remove uremic toxins have emerged, recalcitrant toxins that injure the human body remain a difficult problem. Herein, we review the derivation and elimination of uremic toxins, outline kidney-gut axis function and relative toxin removal methods, and elucidate promising approaches to effectively remove toxins.

Chronic kidney disease (CKD) is a global health challenge affecting nearly 700 million people worldwide. In the United States alone, the Medicare costs for CKD management has reached nearly USD 80 billion per year. While reversing CKD may be possible in the future, current strategies aim to slow its progression. For the most part, current management strategies have focused on employing Renin Angiotensin Aldosterone (RAS) inhibitors and optimizing blood pressure and diabetes mellitus control. Emerging data are showing that a disruption of the gut-kidney axis has a significant impact on delaying CKD progression. Recent investigations have documented promising results in using microbiota-based interventions to better manage CKD. This review will summarize the current evidence and explore future possibilities on the use of probiotics, prebiotics, synbiotics, and fecal microbial transplant to reduce CKD progression.

Tissue engineering and regenerative medicine (TERM) as an emerging field is a multidisciplinary science and combines basic sciences such as biomaterials science, biology, genetics and medical sciences to achieve functional TERM-based products to regenerate or replace damaged or diseased tissues or organs. Probiotics are useful microorganisms which have multiple effective functions on human health. They have some immunomodulatory and biocompatibility effects and improve wound healing. In this article, we describe the latest findings on probiotics and their pro-healing properties on various body systems that are useable in regenerative medicine. Therefore, this review presents a new perspective on the therapeutic potential of probiotics for TERM.

Gut microbial dysbiosis influences the development of sarcopenia. This case-control study explored the gut microbiota composition in elderly Chinese women with sarcopenia. The information from 50 cases and 50 controls was collected. Grip strength, body weight, body mass index, skeletal muscle mass, energy intake, and total and high-quality protein intake were lower in cases than in controls (p < 0.05). Gut microbiota metagenomic sequencing showed that phylum Bacteroides was significantly reduced in the case group, whereas genus Prevotella was more abundant (p < 0.05). Linear discriminant analysis (LDA) effect size showed that 9 and 13 distinct microbial taxa were enriched in the case and control groups, respectively (LDA > 2, p < 0.05), among which Prevotella copri and Bifidobacterium longum were significantly different (LDA > 4, p < 0.05). The AUC of Bifidobacterium longum was 0.674 (95% CI: 0.539-0.756). Elderly women with sarcopenia exhibited significantly different gut microbiota compositions than healthy controls.

Altering dysbiotic gut flora through synbiotic supplementation has recently been recognized as a potential treatment strategy to reduce the levels of gut-derived uremic toxins and decrease inflammation. Assessing its efficacy and safety has been the main goal of our randomized, double-blind, placebo-controlled study.

A total of 34 nondialyzed chronic kidney disease patients, aged ≥18 years, with an estimated glomerular filtration rate between 15 and 45 mL/minute, were randomized either to an intervention group (n = 17), receiving synbiotic (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium lactis, 32 billion colony forming units per day plus 3.2 g of inulin), or control group (n = 17), receiving placebo during 12 weeks. The impact of treatment on the dynamic of serum levels of gut-derived uremic toxins, total serum indoxyl sulfate, p-cresyl sulfate, and trimethylamine N-oxide, was defined as the primary outcome of the study. Secondary outcomes included changes in the stool microbiome, serum interleukin-6 levels, high-sensitivity C-reactive protein, estimated glomerular filtration rate, albuminuria, diet, gastrointestinal symptom dynamics, and safety. Serum levels of uremic toxins were determined using ultraperformance liquid chromatography. The stool microbiome analysis was performed using the 16S ribosomal ribonucleic acid gene sequencing approach.

Synbiotic treatment significantly modified gut microbiome with Bifidobacteria, Lactobacillus, and Subdoligranulum genera enrichment and consequently reduced serum level of indoxyl sulfate (ΔIS -21.5% vs. 5.3%, P < .001), improved estimated glomerular filtration rate (ΔeGFR 12% vs. 8%, P = .029), and decreased level of high-sensitivity C-reactive protein (-39.5 vs. -8.5%, P < .001) in treated patients. Two patients of the intervention arm complained of increased flatulence. No other safety issues were noted.

Synbiotics could be available, safe, and an effective therapeutic strategy we could use in daily practice in order to decrease levels of uremic toxins and microinflammation in chronic kidney disease patients.

Interleukin 17 (IL17)-expressing CD4⁺ T cells and IL-17/IL-23 pathway play a key role in the pathogenesis of axial spondyloarthritis (axSpA). Synbiotics have been suggested due to their immunomodulatory effects in the treatment of autoimmune diseases. This randomized double-blind, placebo-controlled trial was designed to assess the effects of synbiotic supplement on IL-17/IL-23 pathway and disease activity in patients with axSpA.

Forty-eight axSpA patients were randomly allocated to use one synbiotic capsule or placebo daily for 12 weeks. Disease activity was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and ASAS-endorsed disease activity score-C-reactive protein (ASDAS-CRP). The secondary outcome was proportion of IL17-expressing CD4+ T cells, IL-17 and IL-23 gene expression, and supernatant levels of IL-17 and IL-23, which were measured at the baseline and end of the trial.

A total of 48 patients were randomized into the synbiotic and placebo groups. Thirty-eight patients completed the study. Synbiotic supplementation significantly reduced the proportion of IL17-expressing CD4⁺ T cells (4.88 ± 2.47 vs. 2.16 ± 1.25), gene expression of IL-17 (1.03 ± 0.24 vs. 0.65 ± 0.26) and IL-23 (1.01 ± 0.13 vs. 0.68 ± 0.24) and serum IL-17 (38.22 ± 14.40 vs. 24.38 ± 11.68) and IL-23 (51.77 ± 17.40 vs. 32.16 ± 12.46) compared with baseline. Significant differences between groups were noticed only in the proportion of IL17-expressing CD4⁺ T cells, and IL-17 and IL-23 gene expression. Synbiotic supplementation did not significantly alter BASDAI and ASDAS-CRP compared with baseline and placebo group at the end of trial.

Present study indicated beneficial effect of synbiotic supplement on IL-17/IL-23 pathway without improving disease activity in axSpApatients.HighlightsSynbiotic supplementation reduced IL17-expressing CD4⁺ T cells proportion in axSpA.Synbiotic supplementation decreased IL-17 and IL-23 gene expression in axSpA.Synbiotic supplementation did not change disease activity score in axSpA.

Constipation is a common complication in patients with chronic kidney disease (CKD) and is involved in the pathogenesis of dysbiosis and progression of CKD. However, little is known about its association with disorders of the bone-cardiovascular axis in patients with CKD.

We performed a cross-sectional analysis of 3878 patients with CKD using the baseline dataset of the Fukuoka Kidney disease Registry study, as a multicenter, prospective cohort study of pre-dialysis CKD patients. The main exposure of interest was constipation defined as use of at least one type of laxative. The main outcomes were the histories of bone fractures and cardiovascular diseases (CVDs) as manifestations of disorders of the bone-cardiovascular axis.

The prevalences of laxative use and histories of bone fractures and CVDs increased as kidney function declined. Among the 3878 patients, 532 (13.7%) patients used laxatives, 235 (6.1%) patients had prior bone fractures, and 1001 (25.8%) patients had prior CVDs. Histories of bone fractures and CVDs were significantly more prevalent among laxative users (P < 0.05). Multivariable-adjusted logistic regression analysis revealed that patients with laxatives had a significantly higher odds ratios for histories of bone fractures and CVDs than those without laxatives [adjusted odds ratios (95% confidence intervals) 1.67 (1.20-2.31) and 1.70 (1.30-2.22), respectively, P < 0.05].

These results suggest that constipation indicated by laxative use is associated with increased prevalences of historical bone fractures and CVDs in pre-dialysis patients with CKD.

Immune cells and commensal microbes in the human intestine constantly communicate with and react to each other in a stable environment in order to maintain healthy immune activities. Immune system-microbiota cross-talk relies on a complex network of pathways that sustain the balance between immune tolerance and immunogenicity. Probiotic bacteria can interact and stimulate intestinal immune cells and commensal microflora to modulate specific immune functions and immune homeostasis. Growing evidence shows that probiotic bacteria present important health-promoting and immunomodulatory properties. Thus, the use of probiotics might represent a promising approach for improving immune system activities. So far, few studies have been reported on the beneficial immune modulatory effect of probiotics. However, many others, which are mainly focused on their metabolic/nutritional properties, have been published. Therefore, the mechanisms behind the interaction between host immune cells and probiotics have only been partially described. The present review aims to collect and summarize the most recent scientific results and the resulting implications of how probiotic bacteria and immune cells interact to improve immune functions. Hence, a description of the currently known immunomodulatory mechanisms of probiotic bacteria in improving the host immune system is provided.

The current systematic review and meta-analysis investigated the effects of probiotic, prebiotic, and synbiotic administration on inflammation, metabolic parameters, nutritional status, and uremic toxin in dialysis patients.

Up to June 2021, publications were searched in Cochrane Library, PubMed, EMBASE, and Web of Science databases. The protocol was submitted to the International Prospective Register of Systematic Reviews and was approved.

This meta-analysis included 18 randomized controlled trials which were eligible. This meta-analysis discovered that probiotic, prebiotic, and synbiotic supplements could reduce C-reactive protein (standardized mean difference (SMD), -0.38; 95% confidence interval (CI), -0.68 to -0.08; P = .01), interleukin 6 (SMD, -0.48; 95% CI, -0.76 to -0.20; P = .00), and indoxyl sulfate (SMD, -0.24; 95% CI, -0.48 to -0.01; P = .045) and increase high-density lipoprotein cholesterol (SMD, 0.25; 95% CI, 0.03 to 0.46; P = .025) compared with the control group but had no significant influence on tumor necrosis factor α, albumin, hemoglobin, triglyceride, total cholesterol, low-density lipoprotein cholesterol, calcium, phosphorus, uric acid, or p-cresyl sulfate in dialysis patients.

Probiotic, prebiotic, and synbiotic administration could reduce C-reactive protein, interleukin 6, and indoxyl sulfate and increase high-density lipoprotein cholesterol in dialysis patients. To better examine the impact, large-scale, long-term, controlled diets and well-designed randomized controlled trials are needed.

The significance of Bifidobacterium to human health can be appreciated from its early colonization of the neonatal gut, where Bifidobacterium longum represents the most abundant species. While its relative abundance declines with age, it is further reduced in several diseases. Research into the beneficial properties of B. longum has unveiled a range of mechanisms, including the production of bioactive molecules, such as short-chain fatty acids, polysaccharides, and serine protease inhibitors. From its intestinal niche, B. longum can have far-reaching effects in the body influencing immune responses in the lungs and even skin, as well as influencing brain activity. In this review, we present the biological and clinical impacts of this species on a range of human conditions beginning in neonatal life and beyond. The available scientific evidence reveals a strong rationale for continued research and further clinical trials that investigate the ability of B. longum to treat or prevent a range of diseases across the human lifespan.

Diabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Specific remedies are needed for preventing Type 2 diabetes which causes significant changes in an array of plasma metabolites. By untargeted metabolome analysis, phenyl sulfate (PS) increased with the progression of diabetes. In experimental diabetes models, PS administration induces albuminuria and podocyte damage due to the mitochondrial dysfunction. By clinical diabetic kidney disease (DKD) cohort analysis, it was also confirmed that the PS levels significantly correlate with basal and predicted 2-year progression of albuminuria. Phenol is synthesized from dietary tyrosine by gut bacterial-specific tyrosine phenol-lyase (TPL), and absorbed phenol is metabolized into PS in the liver. Inhibition of TPL reduces not only the circulating PS level but also albuminuria in diabetic mice. TPL inhibitor did not significantly alter the major composition, showing the non-lethal inhibition of microbial-specific enzymes has a therapeutic advantage, with lower selective pressure for the development of drug resistance. Clinically, 362 patients in a multi-center clinical study in diabetic nephropathy cohort (U-CARE) were analyzed with full data. The basal plasma PS level significantly correlated with ACR, eGFR, age, duration, HbA1c and uric acid, but not with suPAR. Multiple regression analysis revealed that ACR was the only factor that significantly correlated with PS. By stratified logistic regression analysis, in the microalbuminuria group, PS was the only factor related to the amount of change in the 2-year ACR in all models. PS is not only an early diagnosis marker, but also a modifiable cause and therefore a target for the treatment of DKD. Reduction of microbiota-derived phenol by the inhibitor should represent another aspect for developing drugs of DKD prevention.

This study was conducted on samples from patients enrolled in a randomized double-masked placebo-controlled trial on the effect of synbiotic supplementation on the IL-17/IL-23 pathway and disease activity in patients with axial spondyloarthritis (axSpA) to investigate the effects of synbiotic supplementation on regulatory T (Treg) cells' response in these patients. Forty-eight axSpA patients were randomized to take one synbiotic capsule or placebo daily for 12 weeks. Treg cell proportion, gene expression of forkhead box protein P3 (Foxp3), microRNA (miRNA)-25, miRNA-106b, miRNA-146a, interleukin (IL)-10, and transforming growth factor (TGF)-β as well as serum IL-10 and TGF-β levels were assessed before and after the trial. Thirty-eight patients (19 in each group) completed the trial. The proportion of Treg cells (P < 0.001), the gene expression of FoxP3 (P < 0.001), IL-10 (P = 0.001), TGF-β (P < 0.001), and miRNA-146a (P < 0.001) and serum IL-10 (P = 0.003) and TGF-β (P = 0.002) levels significantly increased compared to the baseline in the synbiotic group. Additionally, a significant reduction in the gene expression of miRNA-25 (P < 0.001) and miRNA-106b (P < 0.001) was observed in the synbiotic group. Significant between-group differences were observed in the proportion of Treg cells (P = 0.024) and the gene expression of FoxP3 (P = 0.010), IL-10 (P = 0.002), TGF-β (P = 0.016), miRNA-25 (P = 0.008), miRNA-106b (P = 0.001), and miRNA-146a (P = 0.010). Differences in the serum levels of IL-10 and TGF-β between the groups were not significant. As a conclusion, synbiotic supplementation could modulate Treg cells' response in axSpA patients and thus can be promising as an adjunctive therapy. Additional investigations would help in further clarifying the subject.

To assess the effect of a probiotic strain Bacillus clausii UBBC-07 on gut microbiota and cytokines in IBD patients.

Patients were randomly allocated to either placebo or probiotic Bacillus clausii UBBC-07 for four weeks along with the standard medical treatment (SMT). Enrolled patients were evaluated before and after intervention for presence of the given probiotic, change in gut microbiota, change in serum cytokines, serotonin and dopamine, symptoms of disease, physical, behavioral and psychological parameters.

Probiotic strain Bacillus clausii UBBC-07 showed good survival in IBD patients in the treatment group (p < 0.01) without any reported adverse event. Metagenomic analysis showed that the given probiotic strain was able to modulate the gut microbiota in treated group. Phylum Firmicutes was increased and phylum Bacteroidetes was decreased in the probiotic treated group. A significant increase was observed in the abundance of anaerobic bacterial genera Lactobacillus, Bifidobacterium and Faecalibacterium in the probiotic treated group (p < 0.01) as compared to placebo group. Significant increase was observed in IL-10 (p < 0.05) and variable decrease in the secretion of IL-1β, TNF- α, IL-6, IL -17 and IL -23 in probiotic treated group. In the treatment group a significant decrease in the symptoms of IBD and improvement in the psychological parameter to various degrees was noted.

These results indicated that probiotic strain B clausii UBBC-07 affected the gut microbiota and cytokine secretion and shown efficacy in IBD patients.

The therapeutic modulation of the gut microbiome has been suggested to be one of the tools in the integrated management of chronic kidney disease (CKD) in recent years. Lactobacillus and Bifidobacterium genera are the two most commonly used probiotics strains. Most of the probiotics used in studies are mixed formulation. There is no consensus on the dose and duration of the probiotic administration for CKD patients Increasing evidence indicates that patients with early stage (1-2) CKD have an altered quantitative and qualitative microbiota profile. However, there was a dearth of prospective controlled studies on the use of probiotics in the early stage of the CKD population. The association between gut microbiota disturbance and advanced CKD was reported. Most randomized controlled trials on probiotic treatment used in CKD stage 3-5ND patients reported positive results. The metabolites of abnormal gut microbiota are directly involved in the pathogenetic mechanisms of cardiovascular disease and inflammation. We summarized 13 studies performed in the dialysis population, including 10 in hemodialysis (HD) patients and 3 in peritoneal dialysis (PD). Some controversial results were concluded on the decreasing plasma concentration of uremic toxin, symptoms, inflammation, and cardiovascular risk. Only three randomized controlled trials on PD were reported to show the potential beneficial effects of probiotics on inflammation, uremic toxins and gastrointestinal symptoms. There is still no standard in the dosage and duration of the use of probiotics in CKD patients. Overall, the probiotic administration may have potential benefit in improving symptoms and quality of life, reducing inflammation, and delaying the progression of kidney failure. Further research studies using a larger sample size with longer follow-up durations and a greater focus on clinical outcomes-including survival-are warranted to elucidate the significant clinical impact of the use of probiotics in CKD patients.

Design, participants, setting, and measurements: Predialysis adult participants with chronic kidney disease (CKD) and mean estimated glomerular filtration rate (eGFR) <45 mL/min per 1.73 m2) were recruited in 2019 to a multicentric double-blinded randomized controlled trial of enzobiotic therapy (synbiotics and proteolytic enzymes) conducted over 12 weeks. The primary objective was to evaluate the efficacy and safety of enzobiotics in reducing the generation of p-cresol sulfate (PCS) and indoxyl sulfate (IS), stabilizing renal function, and improving quality of life (QoL), while the secondary objective was to evaluate the feasibility of the diagnostic prediction of IS and PCS from CKD parameters. Results: Of the 85 patients randomized (age 48.76 years, mean eGFR 23.24 mL/min per 1.73 m2 in the placebo group; age 54.03 years, eGFR 28.93 mL/min per 1.73 m2 in the enzobiotic group), 50 completed the study. The absolute mean value of PCS increased by 12% from 19 µg/mL (Day 0) to 21 µg/mL (Day90) for the placebo group, whereas it decreased by 31% from 23 µg/mL (Day 0) to 16 µg/mL (Day 90) for the enzobiotic group. For IS, the enzobiotic group showed a decrease (6.7%) from 11,668 to 10,888 ng/mL, whereas the placebo group showed an increase (8.8%) from 11,462 to 12,466 ng/mL (Day 90). Each patient improvement ratio for Day 90/Day 0 analysis showed that enzobiotics reduced PCS by 23% (0.77, p = 0.01). IS levels remained unchanged. In the placebo group, PCS increased by 27% (1.27, p = 0.14) and IS increased by 20% (1.20, p = 0.14). The proportion of individuals beyond the risk threshold for PCS (>20 µg/mL) was 53% for the placebo group and 32% for the enzobiotic group. The corresponding levels for IS risk (threshold >20,000 ng/mL) were 35% and 24% for the placebo and enzobiotic groups, respectively. In the placebo group, eGFR decreased by 7% (Day 90) but remained stable (1.00) in the enzobiotic group. QoL as assessed by the adversity ratio decreased significantly (p = 0.00), highlighting an improvement in the enzobiotic group compared to the placebo group. The predictive equations were as follows: PCS (Day 0 = −5.97 + 0.0453 PC + 2.987 UA − 1.310 Creat; IS (Day 0) = 756 + 1143 Creat + 436.0 Creat2. Conclusion: Enzobiotics significantly reduced the PCS and IS, as well as improved the QoL.