The establishment and maintenance of immune homeostasis rely on a dynamic, bidirectional exchange of information between commensal microorganisms and the host immune system. At the center of this process are CD4+Foxp3+ regulatory T cells (Tregs), which have emerged as pivotal mediators to ensure immunological equilibrium. This review explores the sophisticated mechanisms by which the gut microbiota modulates the differentiation, expansion, and functional specialization of Tregs, orchestrating intestinal immune tolerance to support host-microbiota mutualism. We discuss the role of microbial-derived structural components and metabolites in shaping the immunoregulatory fitness of Tregs. Additionally, we explore the impact of gut microbial dysbiosis, where disrupted microbial-immune crosstalk compromises immune tolerance, contributing to the development of inflammatory and autoimmune disorders. Finally, we highlight the potential of microbiota-based strategies to recalibrate intestinal immunity and restore immune tolerance.

Severe acute pancreatitis (SAP)-induced intestinal bacterial translocation and enterogenic infection are among the leading causes of mortality in patients. However, the mechanisms by which SAP disrupted the intestinal barrier and led to bacterial translocation remained unclear. Therefore, we employed multi-omics analysis including microbiome, metabolome, epigenome, transcriptome, and mass cytometry (CyTOF) to identify potential targets, followed by functional validation using transgenic mice. The integrated multi-omics analysis primarily indicated overgrowth of intestinal flagellated bacteria, upregulation of intestinal Toll-like receptor 5 (TLR5) and acute inflammatory response, and increased infiltration of intestinal high-expressing TLR5 lamina propria dendritic cells (TLR5hi LPDC) after SAP. Subsequently, intestinal flagellin-TLR5 signaling was activated after SAP. Intestinal barrier disruption, bacterial translocation, and helper T cells (Th) differentiation imbalance caused by SAP were alleviated in TLR5 knocked out (Tlr5-/-) or conditionally knocked out on LPDC (Tlr5ΔDC) mice. However, TLR5 conditional knockout on intestinal epithelial cells (Tlr5ΔIEC) failed to improve SAP-induced bacterial translocation. Moreover, depletion of LPDC and regulatory T cells (Treg) ameliorated bacterial translocation after SAP. Our findings identify TLR5 on LPDC as a potential novel target for preventing or treating intestinal bacterial translocation caused by SAP.

The human gut hosts a diverse microbial community, essential for maintaining overall health. However, antibiotics, commonly prescribed for infections, can disrupt this delicate balance, leading to antibiotic-associated diarrhea, inflammatory bowel disease, obesity, and even neurological disorders. Recognizing this, probiotics have emerged as a promising strategy to counteract these adverse effects.

This review aims to offer a comprehensive overview of the latest evidence concerning the utilization of probiotics in managing antibiotic-associated side effects.

Probiotics play a crucial role in preserving gut homeostasis, regulating intestinal function and metabolism, and modulating the host immune system. These mechanisms serve to effectively alleviate antibiotic-associated adverse effects and enhance overall well-being.

Gastric cancer is a common malignant tumor, and radical gastrectomy can markedly improve the prognosis of gastric cancer patients. However, some patients are diagnosed with advanced gastric cancer before receiving any antitumor therapy and need to receive neoadjuvant chemotherapy (NACT). Previous studies have shown that NACT may cause gut barrier dysfunction and intestinal dysbacteriosis which may further lead to infections. Probiotics have the potential to reduce postoperative infections and improve short-term outcomes after abdominal surgery; however, no large-sample, multicenter, randomized clinical trials have been conducted to explore the effectiveness of probiotics in gastric cancer patients receiving NACT. So we proposed a hypothesis that probiotics can improve short-term outcomes after minimally invasive radical gastrectomy in gastric cancer patients receiving NACT and designed this multicenter randomized controlled trial with the objective to verify this hypothesis.

The GISSG 2023-01 study will be a prospective, open-label, multicenter RCT to verify whether perioperatively probiotic supplementation (begin from the end of the last cycle of NACT to postoperative day 7 or the discharge day) can reduce postoperative infections and improve recovery of gastrointestinal function and other short-term outcomes after minimally invasive radical gastrectomy in gastric cancer patients receiving NACT. A total of 318 patients who meet the inclusion criteria will be enrolled in this study and randomly divided into two groups in a 1:1 ratio: the probiotic group (n = 159) and the control group (n = 159). The participants in the probiotic group will receive perioperative probiotic supplementation, and those in the control group will receive blank control management. The other perioperative management protocols will be the same between the two groups. The primary outcome is postoperative infection compared between the two groups, and the secondary outcomes are postoperative recovery of gastrointestinal function, quality of life, laboratory parameters of systemic inflammation and other short-term outcomes.

The results of this RCT should clarify whether perioperative probiotic supplementation would reduce postoperative infection, promote recovery of gastrointestinal function, reduce laboratory parameters of systemic inflammation and improve symptoms and quality of life after minimally invasive radical gastrectomy in gastric cancer patients receiving NACT. It is hoped that our data will provide evidence that probiotic supplementation improves short-term outcomes in gastric cancer patients receiving NACT.

This trial has been registered on https://clinicaltrials.gov/(NCT05901779 ).

Acute pancreatitis (AP) is a common and potentially severe gastrointestinal condition characterized by acute inflammation of the pancreas. The pathophysiology of AP is multifactorial and intricate, involving a cascade of events that lead to pancreatic injury and systemic inflammation. The progression of AP is influenced by many factors, including genetic predispositions, environmental triggers, and immune dysregulation. Recent studies showed a critical involvement of the gut microbiota in shaping the immune response and modulating inflammatory processes during AP. This review aims to provide a comprehensive overview of the emerging role of gut microbiota and probiotics in AP. We analyzed the implication of gut microbiota in pathogenesis of AP and the modification during an acute attack. The primary goals of microbiome-based therapies, which include probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and enteral nutrition, are to alter the composition of the gut microbial community and the amount of metabolites derived from the microbiota. By resetting the entire flora or supplementing it with certain beneficial organisms and their byproducts, these therapeutic approaches aim to eradicate harmful microorganisms, reducing inflammation and avoiding bacterial translocation and the potential microbiota-based therapeutic target for AP from nutrition to pre- and probiotic supplementation to fecal transplantation.

This narrative review discusses the mechanisms connecting gut dysbiosis to adverse clinical outcomes in critically ill patients and explores potential therapeutic strategies.

In recent years, the study of microbiota in ICUs has gained attention because of its potential effects on patient outcomes. Critically ill patients often face severe conditions, which can compromise their immune systems and lead to opportunistic infections from bacteria typically harmless to healthy individuals. The relationship between aggressive medical treatments and microbiota composition remains unclear. Dysbiosis, characterized by reduced microbial diversity and the loss of beneficial bacteria, can lead to prolonged immunosuppression and increased pathogenic risks, contributing to infections and organ failure. Recent advancements in multiomics technologies have enhanced the understanding of host-microbe interactions and their implications in critical care.

The microbiota plays an important role in shaping outcomes for critically ill patients. According to evidence, alterations in the gut and lung microbiota are associated with disease severity, mortality, and overall patient recovery. Evolving research opens possibilities for personalized medicine by tailoring treatments based on individual microbiota profiles, though clinical applications are still developing.

Probiotics, live microorganisms with multiple health benefits, have gained popularity for their roles in maintaining daily health and treating a variety of diseases. However, they have the potential to be opportunistic pathogens in some conditions. This review delves into the intrinsic and extrinsic risks associated with probiotics. Intrinsic risks involve the production of harmful substances, such as toxins and invasive factors, biofilm formation, bacteria emboli, antibiotic resistance with relevant genetic materials, genetic plasticity, and metabolic issues, while extrinsic risks include problems in regulatory oversight and public awareness, host health status and appropriately administration. It emphasizes the need for a balanced view of their therapeutic benefits and potential hazards, advocating for further research to understand the complex interactions between probiotics and the human microbiome, to optimize the safety and efficacy of probiotics.

Carboxymethylcellulose (CMC), one of the most common emulsifiers used in the food industry, has been reported to promote chronic inflammatory diseases, but its impact on acute inflammatory diseases, e.g., acute pancreatitis (AP), remains unclear. This study investigates the detrimental effects of CMC on AP and the potential for mitigation through Akkermansia muciniphila or butyrate supplementation.

C57BL/6 mice were given pure water or CMC solution (1%) for 4 weeks and then subjected to caerulein-induced AP. The pancreas, colon, and blood were sampled for molecular and immune parameters associated with AP severity. Gut microbiota composition was assessed using 16S rRNA gene amplicon sequencing. Fecal microbiota transplantation (FMT) was used to illustrate gut microbiota's role in mediating the effects of CMC on host mice. Additional investigations included single-cell RNA sequencing, monocytes-specific C/EBPδ knockdown, LPS blocking, fecal short-chain fatty acids (SCFAs) quantification, and Akkermansia muciniphila or butyrate supplementation. Finally, the gut microbiota of AP patients with different severity was analyzed.

CMC exacerbated AP with gut dysbiosis. FMT from CMC-fed mice transferred such adverse effects to recipient mice, while single-cell analysis showed an increase in classical monocytes in blood. LPS-stimulated C/EBPδ, caused by an impaired gut barrier, drives monocytes towards classical phenotype. LPS antagonist (eritoran), Akkermansia muciniphila or butyrate supplementation ameliorates CMC-induced AP exacerbation. Fecal Akkermansia muciniphila abundance was negatively correlated with AP severity in patients.

This study reveals the detrimental impact of CMC on AP due to gut dysbiosis, with Akkermansia muciniphila or butyrate offering potential therapeutic avenues for counteracting CMC-induced AP exacerbation. Video Abstract.

The rapid proliferation of antimicrobial resistance has emerged as one of the most pressing animal and public health challenges of our time. Probiotics, extensively employed in human and veterinary medicine, are instrumental in maintaining a balanced microbiome and mitigating its disruption during antibiotic therapy. While their numerous benefits are well documented, probiotics also present potential risks, notably the capacity to harbor antimicrobial resistance genes. This genetic reservoir could contribute to the emergence and spread of antimicrobial resistance by facilitating the horizontal transfer of resistance genes to pathogenic bacteria within the gut. This review critically examines the presence of antimicrobial resistance genes in commonly used probiotic strains, explores the underlying mechanisms of resistance, and provides a balanced analysis of the benefits and risks associated with their use. By addressing these dual aspects, this paper highlights the need for vigilant evaluation of probiotics to preserve their therapeutic potential while minimizing public health risks.

Organ failure (OF) is a sinister development in the clinical course of acute pancreatitis, and its prediction is crucial for triaging the patient. Persistent systemic inflammatory response syndrome and raised interleukin-6 levels have a good predictive accuracy. Pathophysiology involves the release of damage-associated molecular patterns as a consequence of pancreatic injury, recruitment of inflammatory cells, and the release of proinflammatory cytokines and chemokines causing cytokine storm. Respiratory system is the most common and earliest to fail. Although a few therapeutic options are in the pipeline, renewed efforts are required to develop targeted therapies to mitigate systemic inflammation and OF.

The initial management of acute pancreatitis (AP) is continually evolving. Goal-directed moderate fluid resuscitation is now preferred over more aggressive strategies. Antibiotics should be administered only when there is a proven or highly probable infection rather than for prophylactic purposes. Urgent endoscopic retrograde cholangiopancreatography would be beneficial for patients with acute cholangitis. Same-admission cholecystectomy for mild biliary PA is safe, efficiently prevents relapse, and is associated with lower costs compared with interval cholecystectomy. Ongoing research into novel pharmacologic treatments and strategies is essential for further advancements in AP management.

The diagnosis, pharmacologic management, and surgical options for Clostridioides difficile infection (CDI) are rapidly evolving, which presents a challenge for the busy surgeon to remain up to date on the latest clinical guidelines. This review provides an evidence-based practical guide for CDI management tailored to the needs of surgeons and surgical intensivists. Historically, the diagnosis of CDI relied on slow cell culture cytotoxicity neutralization assays, but now, the rapidly resulting nucleic acid amplification tests and enzyme immunoassays have become mainstream. In terms of antibiotic therapy, metronidazole and oral vancomycin were the main "workhorse" antibiotics in the early 2000s, but large randomized controlled trials have now demonstrated that fidaxomicin produces superior results. Regarding surgical intervention, total abdominal colectomy was once the only procedure of choice; however, diverting loop ileostomy with colonic lavage is emerging as a viable alternative. Finally, novel adjuncts such as fecal microbiota transplantation and targeted therapy against toxin B (bezlotoxumab) are playing an increasingly important role in the management of CDI.

A. muciniphila (AKK) has attracted extensive research interest as a potential next-generation probiotics, but its role in intestinal pathology is remains unclear. Herein, this study was conducted to investigate the effects of A. muciniphila DSM 22,959 on growth performance, intestinal barrier function, microecology and inflammatory response of weaned piglets stimulated by dextran sulfate sodium salt (DSS).

Twenty-four Duroc × Landrace × Yorkshire (DLY) weaned piglets used for a 2 × 2 factorial arrangement of treatments were divided into four groups with six piglets in each group. From 1 to 15 d, the CA and DA groups were orally fed with 1.0 × 1011 colony-forming units A. muciniphila per day, while the CON and DCON groups were received gastric infusion of anaerobic sterile saline per day. The pigs were orally challenged (DCON, DA) or not (CON, CA) with DSS from day 9 to the end of the experiment and slaughtered on day 16.

Presence of A. muciniphila in DSS-challenged weaned pigs resulted in numerically increased diarrhea rate, blood neutrophilic granulocyte, serum C-reactive protein and immunoglobulin M levels, and numerically reduced final weight, average daily feed intake and average daily gain. The decrease in intestinal villus height, villous height: crypt depth ratio and digestibility was accompanied by lower expression of ZO1, ZO2, Claudin1, DMT1, CAT1, SGLT1 and PBD114 genes, as well as decreased enzyme activities of intestinal alkaline phosphatase, lactase, sucrase and maltase of piglets in DA group compared to piglets in DCON group. The abundance of Bifdobacterium, Lactobacillus, A. muciniphila, Ruminococcus gnavus was numerically higher in digesta of pigs in DA group than those in DCON group. The inflammatory responses of piglets were dramatically changed by the simultaneous presence of A. muciniphila and DSS: expression level of IL17A, IL17F, IL23, RORγt, Stat3 was elevated in DA pigs compared to the other pig groups.

Our result showed that the oral A. muciniphila aggravates DSS-induced health damage of weaned piglet, which may attribute to the deteriorating intestinal morphology, dysbiosis of microbiota and inflammatory response disorders.

The human microbiota plays a crucial role in maintaining overall health and well-being. The gut microbiota has been implicated in developing and progressing various diseases, including cancer. This review highlights the related mechanisms and the compositions that influence cancer pathogenesis with a highlight on gastric cancer. We provide a comprehensive overview of the mechanisms by which the microbiome influences cancer development, progression, and response to treatment, with a focus on identifying potential biomarkers for early detection, prevention strategies, and novel therapeutic interventions that leverage microbiome modulation. This comprehensive review can guide future research and clinical practices in understanding and harnessing the microbiome to optimize gastric cancer therapies.

Animal systematic reviews are critical to inform translational research. Despite their growing popularity, there is a notable lack of information on their quality, scope, and geographical distribution over time. Addressing this gap is important to maintain their effectiveness in fostering medical advancements.

This study aimed to assess the quality and demographic trends of animal systematic reviews in neuroscience, including changes over time.

We performed an umbrella review of animal systematic reviews, searching Medline and Embase for reviews until January 27, 2023. A data mining method was developed and validated to automatically evaluate the quality of these reviews.

From 18'065 records identified, we included 1'358 animal systematic reviews in our study. These reviews commonly focus on translational research but with notable topical gaps such as schizophrenia, other psychiatric disorders, and brain tumours. They originate from 64 countries, with the United States, China, the UK, Brazil, and Iran being the most prolific. The automated quality assessment indicated high reliability, with F1-scores over 80% for most criteria. Overall, the reviews were of high quality and the quality improved over time. However, many systematic reviews did not report a pre-registered study protocol. Reviews with a pre-registered protocol generally scored higher in quality. No significant differences in quality were observed between countries.

Animal systematic reviews in neuroscience are of overall of high quality. Our study highlights specific areas for enhancement such as the recommended pre-publication of study protocols. It also identifies under-represented topics that could benefit from further investigation to inform translational research. Such measures can contribute to the effective translation of animal research findings to clinical applications.

To evaluate the clinical efficacy of probiotics and early oral feeding in patients with severe acute pancreatitis.

A prospective, randomized, controlled trial was conducted involving 66 patients, who were randomly divided into a control group (n = 32) receiving standard enteral nutrition and an observation group (n = 34) receiving additional Bifidobacterium quadruplex live bacterial tablets. Serum inflammatory markers, including white blood cells (WBC), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP), were measured on days 1, 3, and 7 post-admission. Abdominal pain scores, the computed tomography severity index (CTSI), and the Bedside Index for Severity in Acute Pancreatitis (BISAP) scores were also assessed. Additionally, defecation time and the total duration of hospitalization were compared between the two groups.

Inflammatory markers declined in all groups by the third day post-admission, with the observation group exhibiting a significantly greater reduction compared to the control group (p < 0.05). Similarly, from the first day to the third day, both groups experienced a decrease in abdominal pain scores, CTSI, and BISAP scores, with the observation group showing a significantly more pronounced decrease in BISAP scores compared to the control group (p < 0.05). By the seventh day of admission, inflammatory markers continued to decline in all groups compared to the third day, except for TNF-α levels, and the observation group demonstrated a significantly greater decrease compared to the control group (p < 0.05). Abdominal pain scores, CTSI, and BISAP scores also decreased further in both groups compared to the third day, with the observation group again showing a significantly greater improvement than the control group (p < 0.05). Additionally, the observation group had a significantly shorter time to bowel movement resumption (38.23 ± 2.31 h vs. 43.43 ± 2.75 h, p = 0.013) and total hospital stay compared to the control group (10.97 ± 0.35 days vs. 13.40 ± 0.50 days, p < 0.001).

Early oral ingestion combined with probiotics can reduce the levels of inflammatory factors, improve abdominal pain symptoms, alleviate pancreatic edema and shorten defecation time and hospital stay in patients with severe acute pancreatitis.

Probiotics are increasingly being used as an adjunctive therapy for ulcerative colitis. However, some safety issues have been found in the clinical use of probiotics. Postbiotics have attracted much attention due to their storage stability, safety, and potential functions, but the dose required to exert a significant protective effect is unknown. Therefore, this study evaluated the potential mechanisms of different doses (200, 400, 600 mg/kg) of Lactobacillus rhamnosus 1.0320 postbiotics (1.0320P) in alleviating dextran sodium sulfate (DSS)-induced colitis. The study revealed that 1.0320P could mitigate DSS-induced colitis with signs of reductions in the disease activity index, amelioration of colon tissue damage, decreased secretion of proinflammatory cytokines, reduced oxidative stress levels, and lower bone marrow peroxidase activity. Furthermore, high dose of 1.0320P could upregulated the expression of key proteins in the Nrf2/ARE pathway (NQO1, Nrf2, and HO-1) and downregulated the expression of key proteins in the TLR4/NF-κB signaling pathway (TLR4, MyD88, and NF-κB p65). In addition, high dose of 1.0320P could upregulate the expression of tight junction (TJ) proteins including ZO-1, Occludin, and Claudin-1, contributing to the restoration of the intestinal mucosal barrier function. Additionally, 1.0320P was found to effectively correct imbalances in the intestinal microbiota and enhance the synthesis of short-chain fatty acids (SCFAs), thereby regulating homeostasis in the intestinal internal environment. Overall, our findings suggest that postbiotics could ameliorate colonic inflammation while being somewhat dose-dependent. This study provides new insights into postbiotics as a next-generation biotherapeutic agent for the treatment of ulcerative colitis and even other diseases.

The purpose of this review is to provide a practical guide for the clinical care of patients with acute pancreatitis (AP) from the management of the early phases of disease to the treatment of local complications. AP is one of the most frequent causes of gastroenterological admission in emergency departments. It is characterized by a dynamic and unpredictable course and in its most severe forms, is associated with organ dysfunction and/or local complications, requiring intensive care with significant morbidity and mortality. Initial therapy includes adequate fluid resuscitation, nutrition, analgesia, and when necessary critical care support. In recent years, the development of minimally invasive tailored treatments for local complications, such as endoscopic drainage, has improved patients' acceptance and outcomes. Despite this, the management of AP remains a challenge for clinicians. The present review was conducted by the authors, who formulated specific questions addressing the most critical and current aspects of the clinical course of AP with the aim of providing key messages.

Acute pancreatitis (AP) is one of the most common diseases of the gastrointestinal tract, which in 20% of cases can turn into a severe form, with mortality reaching up to 30%. One of the cornerstones of AP treatment is early nutritional treatment. Feeding intolerance (FI) occurs in up to 25% of patients with AP and is associated with a more severe disease course and poorer clinical outcome. Feeding intolerance can have a multifaceted clinical presentation. The early identification of FI risk factors and appropriately conducted nutritional treatment are critical to the course of the disease. In this review, we summarize the current knowledge of feeding intolerance in AP, its pathomechanisms and risk factors, and its impact on disease progression. We also present suggestions for the management of feeding intolerance.

Sepsis is a severe disease that occurs when the body's immune system reacts excessively to infection. The body's response, which includes an intense antibacterial reaction, can damage its tissues and organs. Neutrophils are the major components of white blood cells in circulation, play a vital role in innate immunity while fighting against infections, and are considered a feature determining sepsis classification. There is a plethora of basic research detailing neutrophil functioning, among which, the study of neutrophil extracellular traps is providing novel insights into mechanisms and treatments of sepsis. This review explores their functions, dysfunctions, and influences in the context of sepsis. The interplay between neutrophils and the human microbiome and the impact of DNA methylation on neutrophil function in sepsis are crucial areas of study. The interaction between neutrophils and the human microbiome is complex, particularly in the context of sepsis, where dysbiosis may occur. We highlight the importance of deciphering neutrophils' functional alterations and their epigenetic features in sepsis because it is critical for defining sepsis endotypes and opening up the possibility for novel diagnostic methods and therapy. Specifically, epigenetic signatures are pivotal since they will provide a novel implication for a sepsis diagnostic method when used in combination with the cell-free DNA. Research is exploring how specific patterns of DNA methylation in neutrophils, detectable in cell-free DNA, could serve as biomarkers for the early detection of sepsis.

Lung cancer remains the leading cause of cancer-related deaths worldwide. According to the American Cancer Society (ACS), it ranks as the second most prevalent type of cancer globally. Recent findings have highlighted bidirectional gut-lung interactions, known as the gut-lung axis, in the pathophysiology of lung cancer. Probiotics are live microorganisms that boost host immunity when consumed adequately. The immunoregulatory mechanisms of probiotics are thought to operate through the generation of various metabolites that impact both the gut and distant organs (e.g., the lungs) through blood. Several randomized controlled trials have highlighted the pivotal role of probiotics in gut health especially for the prevention and treatment of malignancies, with a specific emphasis on lung cancer. Current research indicates that probiotic supplementation positively affects patients, leading to a suppression in cancer symptoms and a shortened disease course. While clinical trials validate the therapeutic benefits of probiotics, their precise mechanism of action remains unclear. This narrative review aims to provide a comprehensive overview of the present landscape of probiotics in the management of lung cancer.

This review provides a comprehensive overview of the current state of probiotic research, covering a wide range of topics, including strain identification, functional characterization, preclinical and clinical evaluations, mechanisms of action, therapeutic applications, manufacturing considerations, and future directions. The screening process for potential probiotics involves phenotypic and genomic analysis to identify strains with health-promoting properties while excluding those with any factor that could be harmful to the host. In vitro assays for evaluating probiotic traits such as acid tolerance, bile metabolism, adhesion properties, and antimicrobial effects are described. The review highlights promising findings from in vivo studies on probiotic mitigation of inflammatory bowel diseases, chemotherapy-induced mucositis, dysbiosis, obesity, diabetes, and bone health, primarily through immunomodulation and modulation of the local microbiota in human and animal models. Clinical studies demonstrating beneficial modulation of metabolic diseases and human central nervous system function are also presented. Manufacturing processes significantly impact the growth, viability, and properties of probiotics, and the composition of the product matrix and supplementation with prebiotics or other strains can modify their effects. The lack of regulatory oversight raises concerns about the quality, safety, and labeling accuracy of commercial probiotics, particularly for vulnerable populations. Advancements in multi-omics approaches, especially probiogenomics, will provide a deeper understanding of the mechanisms behind probiotic functionality, allowing for personalized and targeted probiotic therapies. However, it is crucial to simultaneously focus on improving manufacturing practices, implementing quality control standards, and establishing regulatory oversight to ensure the safety and efficacy of probiotic products in the face of increasing therapeutic applications.

Probiotics are known to modulate host immune responses in the course of many diseases. Recently, bacterial extracellular vesicles (EVs), which contain bioactive proteins, lipids, nucleic acids, and metabolites released by bacteria, have been identified as potentially important mediators of bacteria-bacterium and bacteria-host interactions. With the deepening of research, it has been found that probiotic-derived EVs play a significant role in regulating host immune function and, thus, exerting health-promoting effects. Nevertheless, current research is in its early stages, and there remains a long way to go to bridge the gap between basic research and clinical practice. In this review, we describe the fundamental aspects of probiotic-derived EVs, including their biogenesis, cargo sorting mechanism, and transport capabilities. We further discussed the potential mechanisms of probiotic-derived EVs in regulating the host's gut microbiota and immune responses. Finally, we speculate about the potential of probiotic-derived EVs as new postbiotics for applications in functional food, disease treatment substitutes, and immune regulatory adjuvants.

Acute pancreatitis (AP) is increasing in incidence across the world, and in all age groups. Major changes in management have occurred in the last decade. Avoiding total parenteral nutrition and prophylactic antibiotics, avoiding overly aggressive fluid resuscitation, initiating early feeding, avoiding endoscopic retrograde cholangiopancreatography in the absence of concomitant cholangitis, same-admission cholecystectomy, and minimally invasive approaches to infected necrosis should now be standard of care. Increasing recognition of the risk of recurrence of AP, and progression to chronic pancreatitis, along with the unexpectedly high risk of diabetes and exocrine insufficiency after AP is the subject of large ongoing studies. In this review, we provide an update on important changes in management for this increasingly common disease.

Probiotics can alleviate alcoholic liver disease. However, whether inactive counterparts can produce similar outcomes requires further investigation. We investigated the effects of viable (V) and dead (D) Lactobacillus paracasei CCFM1120 on alcohol-induced ALD mice. The results showed that CCFM1120V and D ameliorated the disease symptoms and intestinal injury. Specifically, these interventions strengthened the intestinal barrier, as evidenced by the increased expression of ZO-1 (zonula occludens 1), occludin, and claudin-1 in the colon and the restored ileal microstructure, including the villi and crypts. In addition, they enhanced the antioxidant capacity of the liver by reducing the production of malondialdehyde and increasing the levels of glutathione and superoxide dismutase. The activation of Nrf2 and HO-1 may be responsible for recovering the antioxidant capacity. Interventions can decrease mouse TNF-α, IL-6 and IL-1β content in serum, probably through the TLR4/MyD88/NF-κB pathway. Furthermore, they possess the ability to restore the quantities of bacteria responsible for producing butyric acid, such as Lactobacillus, Blautia, Bifidobacterium, Ruminococcaceae, Faecalibaculum and Lachnospiraceae. Taken together, CCFM1120V and D apparently can modify the composition of the gut microbiota, foster the gastrointestinal equilibrium, fortify the intestinal barrier, augment the antioxidant capacity of the liver, and effectively shield it from ethanol-induced injury.

Nutraceuticals have been described as phytocomplexes when derived from foods of plant origin or a pool of secondary metabolites when derived from foods of animal origin, which are concentrated and administered in an appropriate form and can promote beneficial health effects in the prevention/treatment of diseases. Considering that pharmaceutical medications can cause side effects, there is a growing interest in using nutraceuticals as an adjuvant therapeutic tool for several disorders involving autonomic dysfunction, such as obesity, atherosclerosis and other cardiometabolic diseases. This review summarizes and discusses the evidence from the literature on the effects of various nutraceuticals on autonomic control, addressing the gut microbiota modulation, production of secondary metabolites from bioactive compounds, and improvement of physical and chemical properties of cell membranes. Additionally, the safety of nutraceuticals and prospects are discussed. Probiotics, resveratrol, quercetin, curcumin, nitrate, inositol, L-carnosine, and n-3 polyunsaturated fatty acids (n-3 PUFAs) are among the nutraceuticals most studied to improve autonomic dysfunction in experimental animal models and clinical trials. Further human studies are needed to elucidate the effects of nutraceuticals formulated of multitarget compounds and their underlying mechanisms of action, which could benefit conditions involving autonomic dysfunction.

According to the Centers for Disease Control and Prevention and governing bodies within the American College of Surgeons, the administration of antibiotics as prophylaxis against infection prior to a planned elective procedure is, with rare exception, routinely recommended. The goal of "getting to zero" infections remains a high priority for policymakers, practitioners, and certainly for patients.

Despite the many advances in surgical technique, skin decontamination, sterile procedure, and enhanced recovery programs, surgical site infections continue to adversely affect procedures as diverse as dental implant surgery, joint arthroplasty, and major abdominal surgery. Although surgical site infection rates are at historically low levels, progress has stalled in recent reporting periods and such infections remain disabling, costly, and occasionally lethal. Stakeholders in the field, including surgeons, infectious diseases specialists, and industry, advocate for strategies emphasizing greater levels of intraoperative sterility or broader-spectrum antibiotic coverage as the most appropriate path forward.

The current emphasis on ever-increasing levels of intraoperative sterility and extended-spectrum antibiotic use are not sustainable long-term solutions. Continuing to escalate these approaches may contribute to unintended consequences including antimicrobial resistance. Principles of antimicrobial stewardship and microbiome sciences can be applied to inform a more effective and sustainable approach to infection prevention in the field of surgery.

Clostridioides difficile is the main causative agent of antibiotic-associated diarrhea (AAD) in hospitals in the developed world. Both infected patients and asymptomatic colonized individuals represent important transmission sources of C. difficile. C. difficile infection (CDI) shows a large range of symptoms, from mild diarrhea to severe manifestations such as pseudomembranous colitis. Epidemiological changes in CDIs have been observed in the last two decades, with the emergence of highly virulent types and more numerous and severe CDI cases in the community. C. difficile interacts with the gut microbiota throughout its entire life cycle, and the C. difficile's role as colonizer or invader largely depends on alterations in the gut microbiota, which C. difficile itself can promote and maintain. The restoration of the gut microbiota to a healthy state is considered potentially effective for the prevention and treatment of CDI. Besides a fecal microbiota transplantation (FMT), many other approaches to re-establishing intestinal eubiosis are currently under investigation. This review aims to explore current data on C. difficile and gut microbiota changes in colonized individuals and infected patients with a consideration of the recent emergence of highly virulent C. difficile types, with an overview of the microbial interventions used to restore the human gut microbiota.

Abrupt dietary change can disrupt the intestinal balance in felines. This study aimed to assess the impact of heat-treated Bifidobacterium longum CECT-7347 combined with Fibersol-2 on the intestinal health of adult cats before and after dietary change. We selected 24 British shorthair cats, dividing them into two groups. From day 1 to day 14, the control group received a lower protein (33%) concentration (LPF) diet, while the treated group received the same LPF diet supplemented with 0.16% functional additives, consisting of Bifidobacterium longum CECT-7347 combined with Fibersol-2. Subsequently, from day 15 to day 28, the control group transitioned to a higher protein (40%) concentration (HPF) diet, while the treated group received the same HPF diet supplemented with 0.16% functional additives. Blood and fresh feces were collected on day 0, 14, 17, 21, and 28 of the experiment. The results suggest that the use of heat-treated Bifidobacterium longum CECT-7347 combined with Fibersol-2 may improve gastrointestinal function in cats by reducing serum LPS levels and fecal pH, while increasing fecal sIgA levels. In addition, the functional additive regulates the fecal microbiota and its function, promoting intestinal homeostasis and colonization with beneficial bacteria such as Blautia. Furthermore, on day 28, there was a significant difference in fecal microbiota beta diversity between the two groups. In summary, the addition of heat-treated Bifidobacterium longum CECT-7347 combined with Fibersol-2 contributes to improving the intestinal health of adult cats affected by abrupt dietary change.

The study examines the integration of postbiotics in food products through the use of attenuated probiotics, specifically lactic acid bacteria (LAB) in bread. Postbiotics, non-viable microorganisms or their metabolites, offer health benefits similar to probiotics without the risks associated with live bacteria. This research evaluates the regulatory aspects and safety of LAB in sourdough bread production, highlighting their historical and significant use in Europe before 1997. The study includes microbial quantification and Next-Generation Sequencing (NGS) to identify LAB in traditional sourdough, comparing them with historical and current EFSA Qualified Presumption of Safety (QPS) lists. Findings show that the LAB present in sourdough have been extensively and safely used in bread making, supporting their classification as non-novel foods under EU regulations. The stability and consistency of LAB metabolites in sourdough bread are also confirmed, ensuring quality and safety in each batch. The study concludes that LAB in sourdough, when inactivated through bread-making processes, are not considered novel foods, aligning with historical, scientific, and regulatory evidence.

There are many options for the reduction of portal hypertension (pH) in cirrhotic patients, but all the current ones have side effects. Probiotics are a new approach for ameliorating the hyperdynamic circulation of cirrhotic patients. The aim of this study is to measure the effect of probiotics on pH in cirrhosis for the first time.

A search was conducted across four electronic databases (PubMed, Scopus, Web of Science, Cochrane) for English-language records evaluating probiotic effects on pH in cirrhotic patients. Quality assessment used the Cochrane Collaboration's tool, employing a random-effects model in statistical analysis with Stata software version 1.

A search yielded 1,251 articles, which were narrowed down to 5 through screening. These studies, involving 158 participants across Canada, India, Spain, and Russia, focused on probiotic interventions in cirrhotic patients. Meta-analysis of two RCTs (66 participants) indicated a significant decrease in hepatic venous pressure gradient (HVPG) (SMD: -0.60 [-1.09, -0.12]). In single-arm analysis, four studies (58 participants) showed a substantial reduction in HVPG with probiotic use compared to the control (SMD: -2.55 [-3.42, -1.68]).

In summary, it showcased a notable reduction in HVPG compared to the control group, indicating a potential advantage of probiotics in decreasing pH in cirrhotic patients. Further research with larger samples and robust designs is warranted.

The early provision of soluble/insoluble fiber to the patient who is critically ill has been controversial in the past. Especially in the setting of hemodynamic instability, dysmotility, or impaired gastrointestinal transit, fear of inspissation of formula with precipitation of nonocclusive mesenteric ischemia (NOMI)/nonocclusive bowel necrosis (NOBN) limited its utilization by medical and surgical intensivists. The incidence of NOMI/NOBN has been estimated at 0.2%-0.3% for all intensive care unit (ICU) patients receiving enteral nutrition (EN), and the occurrence of inspissated formula is even less. The science supporting a benefit from providing fiber has recently increased exponentially. The fermentation of soluble fibers leading to the production of short chain fatty acids supports gut barrier function, modulates immune responses, and promotes refaunation of commensal organisms. The "butyrate effect" refers to local (gastrointestinal tract) and systemic anti-inflammatory responses mediated by the M2 polarization of macrophages, inhibition of histone deacetylase, and stimulation of ubiquitous G protein receptors. Both soluble and insoluble fiber have been shown to promote intestinal motility, reduce feeding intolerance, and shorten hospital length of stay. The benefit of providing dietary fiber early upon admission to the ICU outweighs its minimal associated risk. The point at which the intensivist determines that is safe to initiate EN, both soluble and insoluble fiber should be included in the enteral formulation.

Chronic constipation is a common disease that can impair the quality of life, with a prevalence of 14% globally and 16.5% in South Korea. Straining, hard stools, the sensation of incomplete evacuation, the sensation of anorectal blockage, and manual maneuvers to facilitate defecation are the related symptoms of chronic constipation. On the other hand, medications commonly referred to as laxatives are the essentials of treatment for constipation compared to non-pharmacological treatment, such as lifestyle modifications, biofeedback, or surgery. Unfortunately, there is still an unmet need to determine if pharmacological treatment for constipation is being administered appropriately. Therefore, there are many disadvantages as to whether the indications and side effects of laxatives are adequately considered and prescribed as the primary treatment modality for constipation in a real clinical situation in Korea. Laxatives are generally recommended as the next step for patients in whom organic causes have been excluded and have not responded to initial non-pharmacologic therapies such as dietary fiber intake and exercise. Laxatives can be classified as bulk-forming laxatives, osmotic laxatives, stimulant laxatives, and other novel laxatives. On the other hand, there are distinct mechanisms underlying constipation, and appropriate administration is the most decisive. Therefore, the present investigators prepared this review to discuss appropriate pharmacological strategies for chronic constipation in Korea. Moreover, this paper also includes suggestions for appropriate pharmacological treatment options for special patient populations.

The beneficial effects of probiotics, postbiotics, and paraprobiotics have already been registered in managing ischemic stroke-generated neuroinflammation and gut dysbiosis. Herein, we examined the impact of cell-free supernatant (CFS) obtained from probiotics (Lactobacillus rhamnosus UBLR-58 and Bifidobacterium breve UBBr-01) in a rat transient middle cerebral artery occlusion (MCAO) model of focal cerebral injury. Pre-MCAO supplementation of probiotics (2 × 109 CFU/mL) for 21 days or CFS (1 mL/rat) for 7 days protect the MCAO-induced somatosensory and motor impairments recorded at 24 h and 72 h after reperfusion in foot-fault, rotarod, adhesive removal, and vibrissae-evoked forelimb placing tests. We also noted the reduced infarct area and neuronal degradation in the right hemisphere of probiotics- and CFS-recipient MCAO-operated animals. Moreover, MCAO-induced altered concentrations of glial-fibrillary acidic protein, NeuN, zonula occludens-1 (ZO-1), TLR4, IL-1β, IL-6, and TNF-α, as well as matrix metalloproteinase-9 (MMP9) were reversed in the treatment groups. Probiotics and CFS treatment ameliorated the elevated levels of IL-6, IL-1β, and MMP9 in the blood plasma of rats. The disrupted microbial phyla, Firmicutes-to-Bacteroides ratio, villi/crypt ratio, and decreased mucin-producing goblet cells, ZO-1, and occludin in the colon of MCAO-operated rats were recovered following probiotics and CFS treatment. NMR characterization of CFS and rat blood plasma revealed the presence of several important bacterial metabolites. These findings suggest that the CFS obtained from Lactobacillus rhamnosus UBLR-58 and Bifidobacterium breve UBBr-01 has the propensity to improve MCAO-generated neurological dysfunctions in rats by dampening neuroinflammation and modulating the gut-brain axis modulators.

The long-term impact of perioperative probiotics remains understudied while mounting evidence links microbiome and oncogenesis. Therefore, we analyzed overall survival and cancer recurrence among patients enrolled in a randomized trial of perioperative probiotics.

6-year follow-up of surgical patients participating in a randomized trial evaluating short-course perioperative oral probiotic VSL#3 (n = 57) or placebo (n = 63).

Study groups did not differ in age, preoperative hemoglobin, ASA status, and Charlson comorbidity index. There was a significant difference in preoperative serum albumin (placebo group 4.0 ± 0.1 vs. 3.7 ± 0.1 g/dL in the probiotic group, p = 0.030). Thirty-seven deaths (30.8 %) have occurred during a median follow-up of 6.2 years. Overall survival stratified on preoperative serum albumin and surgical specialty was similar between groups (p = 0.691). Age (aHR = 1.081, p = 0.001), serum albumin (aHR = 0.162, p = 0.001), and surgical specialty (aHR = 0.304, p < 0.001) were the only predictors of overall survival in the multivariate model, while the placebo/probiotic group (aHR = 0.808, p = 0.726) was not predictive. The progression rate among cancer patients was similar in the probiotic group (30.3 %, 10/33) compared to the placebo group (21.2 %, 7/33; p = 0.398). The progression-free survival was not significantly different (unstratified p = 0.270, stratified p = 0.317).

Perioperative short-course use of VSL#3 probiotics does not influence overall or progression-free survival after complex surgery for visceral malignancy.

Nutrition plays an important role in management of acute pancreatitis (AP) and decreases its severity and infectious complications. Various formulations of enteral nutrition (EN) are available and are costly. For developing countries, cost and availability is a major issue and kitchen-based diet should be explored in patients with AP.

Comparison of kitchen-based diet with a commercially available polymeric formulation in terms of various outcomes in patients with AP within 14 days after the onset of pain.

Sixty patients (39 male, mean age 36.1 ± 12.7 years) of moderately severe and severe AP of any etiology were randomized (30 in each group) to either kitchen-based diet or commercial polymeric formulation group. Outcome measures were refeeding pain, tolerability, infectious complications, mortality, total hospital/intensive care unit stay; and change in serum C-reactive protein (CRP), transferrin and pre albumin.

There was no significant difference in baseline demographic and biochemical parameters in both groups. No difference was observed in refeeding pain (7.1% vs 8%, p = 0.99), tolerability (28.6% vs 12%, p = 0.17), infectious complications (57.14% vs 36%, p = 0.12), mortality (31.7% vs 20%, p = 0.69), hospital stay (19.5 vs 23.5 days, p = 0.86), CRP (74.4 vs 59 mg/L, p = 0.97), transferrin levels (23.6 vs 25.6 mg/dL, p = 0.75) and pre albumin (9.45 vs 13.09 mg/dL, p = 0.68) in both groups.

Kitchen-based diet is comparable to commercial polymeric formulation for the early initiation of enteral nutrition in patients with severe or moderately severe acute pancreatitis.

Trial registered with the Clinical Trials registry-India (CTRI/2018/01/011188).

Postmenopausal osteoporosis is caused by estrogen deficiency, which impairs bone homeostasis, resulting in increased osteoclastic resorption without a corresponding increase in osteoblastic activity. Postbiotics have several therapeutic properties, including anti-obesity, anti-diabetic, anti-inflammatory, and anti-osteoporotic effects. However, the beneficial effects of the postbiotic MD35 of Lactobacillus plantarum on bone have not been studied. In this study, we demonstrated that the postbiotic L. plantarum MD35, isolated from young radish water kimchi, influences osteoclast differentiation in mouse bone marrow-derived macrophage (BMM) culture. In addition, it was effective protecting against estrogen deficiency-induced bone loss in ovariectomized (OVX) mice, an animal model of postmenopausal osteoporosis. In BMM cells, postbiotic MD35 inhibited the receptor activator of nuclear factor-kappa B of NF-κB ligand (RANKL)-induced osteoclast differentiation by attenuating the phosphorylation of extracellular signal-related kinase, significantly suppressing the resorption activity and down-regulating the expression of RANKL-mediated osteoclast-related genes. In the animal model, the oral administration of postbiotic MD35 remarkably improved OVX-induced trabecular bone loss and alleviated the destruction of femoral plate growth. Therefore, postbiotic MD35 could be a potential therapeutic candidate for postmenopausal osteoporosis by suppressing osteoclastogenesis through the regulation of osteoclast-related molecular mechanisms.

Clostridioides difficile (C. difficile) is a spore-forming bacterial species that ubiquitously exists in the environment. Colonization by C. difficile is highly prevalent in infants, while fewer than 5% of adults are asymptomatic carriers. Disruption of the microbiome, such as through antibiotic treatment, triggers the germination of bacterial spores into numerous vegetative cells. These cells then produce enterotoxins that result in watery diarrhea and colonic inflammation. If left untreated, C. difficile infection (CDI) can lead to pseudomembranous colitis with the potentially life-threatening complication of toxic megacolon.

Over the past few decades, the incidence, morbidity, and mortality associated with CDIs have increased. They have emerged as the primary cause of nosocomial gastrointestinal infections in industrialized countries, posing a significant burden on healthcare systems. Despite antibiotics often being the cause of CDIs, they remain the standard treatment. However, a considerable number of patients treated with antibiotics will experience recurrent CDI (rCDI). Microbiota-based therapies targeting the core issue of CDI - antibiotic-induced dysbiosis - hold promise for rCDI treatment. While data for probiotics are insufficient, numerous studies have highlighted the effectiveness of fecal microbiota transplantation (FMT) as a safe and viable therapeutic option for rCDI. This approach is now endorsed by multiple guidelines. Nonetheless, regulatory prerequisites, such as comprehensive stool donor screening, restrict the widespread adoption of FMT beyond specialized centers. Recently, the US Food and Drug Administration has approved two commercial microbiota-based therapeutics to prevent CDI recurrence. These therapeutics are available by prescription in the USA. RBX2660 (REBYOTA™) comprises a diverse consortium of live microbes derived from human stool and is administered via enema. On the other hand, SER-109 (VOWST™) is an orally administered spore-based medication. In this review, we discuss the potential of microbiota-based treatments for rCDI against the background of medico-legal challenges associated with classical FMT.

FMT has emerged as a highly effective cure for rCDI. Nonetheless, regulatory prerequisites and laborious preparation procedures impede its widespread use. The establishment of ready-to-use microbiota-based therapeutics in clinical practice is necessary. In the USA, the recent approval of the first two commercial medications, including a spore-based oral preparation, marks a significant step forward.

The gut microbiota is emerging as an important contributor to the homeostasis of the human body through its involvement in nutrition and metabolism, protection against pathogens, and the development and modulation of the immune system. It has therefore become an important research topic in recent decades. Although the association between intestinal dysbiosis and numerous digestive pathologies has been thoroughly researched, its involvement in pancreatic diseases constitutes a novelty in the specialized literature. In recent years, growing evidence has pointed to the critical involvement of the pancreas in regulating the intestinal microbiota, as well as the impact of the intestinal microbiota on pancreatic physiology, which implies the existence of a bidirectional connection known as the "gut-pancreas axis". It is theorized that any change at either of these levels triggers a response in the other component, hence leading to the evolution of pancreatitis. However, there are not enough data to determine whether gut dysbiosis is an underlying cause or a result of pancreatitis; therefore, more research is needed in this area. The purpose of this narrative review is to highlight the role of gut dysbiosis in the pathogenesis of acute and chronic pancreatitis, its evolution, and the prospect of employing the microbiota as a therapeutic intervention for pancreatitis.