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.

Fecal microbiota transplantation (FMT) represents a therapeutic approach that directly regulates the gut microbiota of recipients, normalizes its composition and reaping therapeutic rewards. Currently, in addition to its general application in treating Clostridium difficile (C. difficile) infection (CDI), FMT treatment has also been extended to the fields of other gastrointestinal diseases, infections, gut-liver or gut-brain axis disorders, metabolic diseases and cancer, etc. Prior to FMT, rigorous donor screening is essential to reduce the occurrence of adverse events. In addition, it is imperative to evaluate whether the recipient can safely and effectively undergo FMT treatment. However, the efficacy of FMT is influenced by the complex interactions between the gut microbiota of donor and recipient, the degree of donor microbiota engraftment is not necessarily positively related with the success rate of FMT. Furthermore, an increasing number of novel factors affecting FMT outcomes are being identified in recent clinical trials and animal experiments, broadening our understanding of FMT treatment. This article provides a comprehensive review of the application scenarios of FMT, the factors influencing the safety and efficacy of FMT from the aspects of both the donors and the recipients, and summarizes how these emerging novel regulatory factors can be combined to predict the clinical outcomes of patients undergoing FMT.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a condition wherein excessive fat accumulates in the liver, leading to inflammation and potential liver damage. In this narrative review, we evaluate the tissue microbiota, how they arise and their constituent microbes, and the role of the intestinal and hepatic microbiota in MASLD. The history of bacteriophages (phages) and their occurrence in the microbiota, their part in the potential causation of MASLD, and conversely, "phage therapy" for antibiotic resistance, obesity, and MASLD, are all described. The microbiota metabolism of bile acids and dietary tryptophan and histidine is defined, together with the impacts of their individual metabolites on MASLD pathogenesis. Both periodontitis and intestinal microbiota dysbiosis may cause MASLD, and how individual microorganisms and their metabolites are involved in these processes is discussed. Novel treatment opportunities for MASLD involving the microbiota exist and include fecal microbiota transplantation, probiotics, prebiotics, synbiotics, tryptophan dietary supplements, intermittent fasting, and phages or their holins and endolysins. Although FDA is yet to approve phage therapy in clinical use, there are multiple FDA-approved clinical trials, and this may represent a new horizon for the future treatment of MASLD.

This study highlights the importance of identifying and addressing risk factors associated with wound complications following transtibial amputation in diabetic patients. These amputations, often necessitated by severe diabetic foot ulcers, carry significant risks of postoperative complications such as infection and delayed wound healing. Elevated hemoglobin A1c levels, indicative of poor glycemic control, and a history of kidney transplantation, due to required immunosuppressive therapy, are key factors influencing these outcomes. This paper emphasizes the need for enhanced glycemic management and personalized postoperative care, particularly for immunocompromised individuals, to minimize complications and improve patient prognosis. Future research should focus on prospective studies to validate targeted interventions and optimize care strategies, ultimately aiming to reduce the healthcare burden associated with diabetic foot complications.

Parasitic infections are a major global health challenge, driven in part by complex interactions between parasites, host microbiota, and immune responses. Recent advances in microbiome research highlight the critical role of microbiota in influencing disease outcomes and treatment effectiveness. This review examines how changes in the microbiota impact parasite transmission, disease progression, and responses to treatment, focusing on key parasitic diseases such as Chagas disease, leishmaniasis, and ascariasis. The microbiota can either exacerbate or mitigate disease severity, depending on its composition, providing critical insights for novel therapeutic strategies. Emerging approaches discussed include the use of targeted probiotics, prebiotics, and microbiota-modulating drugs to influence parasite dynamics and enhance conventional therapies. The review also explores the potential of integrating microbiota knowledge into vaccine design and immunotherapy, aiming to develop vaccines that elicit stronger immune responses and identify new therapeutic targets. A multidisciplinary approach is essential for translating these findings into effective clinical solutions, with future research focusing on validating microbiota-based interventions in clinical settings. In conclusion, the interaction between microbiota and parasitic infections presents a promising avenue for innovative therapies, with the potential to significantly improve global health outcomes.

Organ transplantation is a vital intervention for end-stage organ failure; however, ischemia-reperfusion injury is a complication of transplantation, affecting the prognosis and survival of transplant recipients. As a complex ecosystem, recent research has highlighted the role of the intestinal microecology in transplantation, revealing its significant interplay with ischemia-reperfusion injury. This review explores the interaction between ischemia-reperfusion injury and intestinal microecology, with a special focus on how ischemia-reperfusion injury affects intestinal microecology and how these microecological changes contribute to complications after organ transplantation, such as infection and rejection. Based on a comprehensive analysis of current research advances, this study proposes potential strategies to improve transplant outcomes, offering guidance for future research and clinical practice.

The human gastrointestinal (GI) tract microbiome is a complex and all-encompassing ecological system of trillions of microorganisms. It plays a vital role in digestion, disease prevention, and overall health. When this delicate balance is disrupted, it can lead to various health issues. Fecal microbiota transplantation (FMT) is an emerging therapeutic intervention used as an adjuvant therapy for many diseases, particularly those with dysbiosis as their underlying cause. Its goal is to restore this balance by transferring fecal material from healthy donors to the recipients. FMT has an impressive reported cure rate between 80% and 90% and has become a favored treatment for many diseases. While FMT may have generally mild to moderate transient adverse effects, rare severe complications underscore the importance of rigorous donor screening and standardized administration. FMT has enormous potential as a practical therapeutic approach; however, additional research is required to further determine its potential for clinical utilization, as well as its safety and efficiency in different patient populations. This comprehensive literature review offers increased confidence in the safety and effectiveness of FMT for several diseases affecting the intestines and other systems, including diabetes, obesity, inflammatory and autoimmune illness, and other conditions.

Kidney transplantation is an effective way to improve the condition of patients with end-stage renal disease. However, maintaining long-term graft function and improving patient survival remain a key challenge after kidney transplantation. Dysbiosis of intestinal flora has been reported to be associated with complications in renal transplant recipients. The commensal microbiota plays an important role in the immunomodulation of the transplant recipient responses. However, several processes, such as the use of perioperative antibiotics and high-dose immunosuppressants in renal transplant recipients, can lead to gut dysbiosis and disrupt the interaction between the microbiota and the host immune responses, which in turn can lead to complications such as infection and rejection in organ recipients. In this review, we summarize and discuss the changes in intestinal flora and their influencing factors in patients after renal transplantation as well as the evidence related to the impact of intestinal dysbiosis on the prognosis of renal transplantation from in vivo and clinical studies, and conclude with a discussion of the use of microbial therapy in the transplant population. Hopefully, a deeper understanding of the function and composition of the microbiota in patients after renal transplantation may assist in the development of clinical strategies to restore a normal microbiota and facilitate the clinical management of grafts in the future.

Fecal microbiota transplantation (FMT) is recommended for the treatment of recurrent Clostridioides difficile infection (rCDI). In the current study, we evaluated rates of rCDI and subsequent FMT in a large metropolitan area. We compared demographic and clinical differences in FMT recipients and nonrecipients and quantified differences in outcomes based on treatment modality.

A retrospective community-wide cohort study was conducted using surveillance data from the Georgia Emerging Infections Program, the Georgia Discharge Data System, and locally maintained lists of FMTs completed across multiple institutions to evaluate all episodes of C. difficile infection (CDI) in this region between 2016 and 2019. Cases were limited to patients with rCDI and ≥1 documented hospitalization. A propensity-matched cohort was created to compare rates of recurrence and mortality among matched patients based on FMT receipt.

A total of 3038 (22%) of 13 852 patients with CDI had rCDI during this period. In a propensity-matched cohort, patients who received an FMT had lower rates of rCDI (odds ratio, 0.6 [95% confidence interval, .38-.96) and a lower mortality rate (0.26 [.08-.82]). Of patients with rCDI, only 6% had received FMT. Recipients were more likely to be young, white, and female and less likely to have renal disease, diabetes, or liver disease, though these chronic illnesses were associated with higher rates of rCDI.

These data suggest FMT has been underused in a population-based assessment and that FMT substantially reduced risk of recurrence and death.

SUMMARYClostridioides difficile infection (CDI) is one of the major issues in nosocomial infections. This bacterium is constantly evolving and poses complex challenges for clinicians, often encountered in real-life scenarios. In the face of CDI, we are increasingly equipped with new therapeutic strategies, such as monoclonal antibodies and live biotherapeutic products, which need to be thoroughly understood to fully harness their benefits. Moreover, interesting options are currently under study for the future, including bacteriophages, vaccines, and antibiotic inhibitors. Surveillance and prevention strategies continue to play a pivotal role in limiting the spread of the infection. In this review, we aim to provide the reader with a comprehensive overview of epidemiological aspects, predisposing factors, clinical manifestations, diagnostic tools, and current and future prophylactic and therapeutic options for C. difficile infection.

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

Background: Improvements in liver transplant (LT) outcomes are attributed to advances in surgical techniques, use of potent immunosuppressants, and rigorous pre-LT testing. Despite these improvements, post-LT infections remain the most common complication in this population. Bacteria constitute the most common infectious agents, while fungal and viral infections are also frequently encountered. Multi-drug-resistant bacterial infections develop because of polymicrobial overuse and prolonged hospital stays. Immediate post-LT infections are commonly caused by viruses. Conclusions: Appropriate vaccination, screening of both donor and recipients before LT and antiviral prophylaxis in high-risk individuals are recommended. Antimicrobial drug resistance is common in high-risk LT and associated with poor outcomes; epidemiology and management of these cases is discussed. Additionally, we also discuss the effect of coronavirus disease 2019 (COVID-19) infection and monkeypox in the LT population.

Strong clinical data demonstrate that inflammatory bowel disease (IBD) is an independent risk factor for Clostridiodes difficile infection (CDI) and suggest a globally increased prevalence and severity of C. difficile coinfection in IBD patients (CDI-IBD). In addition to elderly individuals, children are also at higher risk of CDI-IBD. Rapid diagnosis is essential since the clinical manifestations of active IBD and CDI-IBD are indistinguishable. Antibiotics have been well established in the treatment of CDI-IBD, but they do not prevent recurrence.

Herein, the authors focus on reviewing recent research advances on the new therapies of CDI-IBD. The novel therapies include gut microbiota restoration therapies (such as prebiotics, probiotics and FMT), immunotherapy (such as vaccines and monoclonal antibodies) and diet strategies (such as groningen anti-inflammatory diet and mediterranean diet). Future extensive prospective and placebo-controlled studies are required to evaluate their efficacy and long-term safety.

Available studies show that the prevalence of CDI-IBD is not optimistic. Currently, potential treatment options for CDI-IBD include a number of probiotics and novel antibiotics. This review updates the knowledge on the management of CDI in IBD patients, which is timely and important for GI doctors and scientists.

Recurrent Clostridium difficile infection (rCDI) is a rising problem in children with chronic diseases. Fecal microbiota transplantation (FMT) is a recent alternative for rCDI patients who do not respond to conventional treatment. FMT could have an additional positive effect on the intestinal dysbiosis and accumulation of uremic retention molecules (URM) associated with chronic kidney disease (CKD). Our aim was to investigate the clinical efficacy of FMT for rCDI in children with CKD together with the effect on dysbiosis and URM levels.

We analyzed stool and blood samples before and until 3 months after FMT in 3 children between 4 and 8 years old with CKD and rCDI. The microbiome was analyzed by 16 s rRNA sequencing. URM were analyzed with ultra-performance liquid chromatography-tandem mass spectrometry. CRP and fecal calprotectin were analyzed as parameters for systemic and gut inflammation, respectively.

CDI resolved after FMT in all three without adverse events; one patient needed a second FMT. No significant effect on CRP and calprotectin was observed. Stool samples demonstrated a reduced richness and bacterial diversity which did not improve after FMT. We did observe a trend in the decrease of specific URM up to 3 months after FMT.

FMT is an effective treatment for rCDI in patients with CKD. Analysis of the microbiome showed an important intestinal dysbiosis that, besides a significant reduction in Clostridium difficile, did not significantly change after FMT. A trend for reduction was seen in some of the measured URM after FMT.

Gut microbiota is often modified after kidney transplantation. This principally happens in the first period after transplantation. Antibiotics and, most of all, immunosuppressive drugs are the main responsible. The relationship between immunosuppressive drugs and the gut microbiota is bilateral. From one side immunosuppressive drugs modify the gut microbiota, often generating dysbiosis; from the other side microbiota may interfere with the immunosuppressant pharmacokinetics, producing products more or less active with respect to the original drug. These phenomena have influence over the graft outcomes and clinical consequences as rejections, infections, diarrhea may be caused by the dysbiotic condition. Corticosteroids, calcineurin inhibitors such as tacrolimus and cyclosporine, mycophenolate mofetil and mTOR inhibitors are the immunosuppressive drugs whose effect on the gut microbiota is better known. In contrast is well known how the gut microbiota may interfere with glucocorticoids, which may be transformed into androgens. Tacrolimus may be transformed by micro biota into a product called M1 that is 15-fold less active with respect to tacrolimus. The pro-drug mycophenolate mofetil is normally transformed in mycophenolic acid that according the presence or not of microbes producing the enzyme glu curonidase, may be transformed into the inactive product.

The European Society of Clinical Microbiology and Infectious Disease (ESCMID) has advised against the use of metronidazole for fulminant Clostridioides difficile (C. difficile) infection (CDI) in their latest guidelines. They suggest using oral vancomycin alone instead. This recommendation is based on a few retrospective studies, which have multiple biases. We evaluated the three studies that led ESCMID to advise against intravenous metronidazole for fulminant CDI and performed a meta-analysis. The meta-analysis revealed a mild (2.7%), not statistically significant (p=0.8) difference in mortality between the two groups. The high heterogeneity (I2= 89%) should also be noted. The decision to add or remove metronidazole should be discussed in the near future. In the meantime, combination therapy could be a cautious treatment for fulminant CDI.

Fecal microbiota-based therapies include conventional fecal microbiota transplant and US Food and Drug Administration-approved therapies, fecal microbiota live-jslm and fecal microbiota spores live-brpk. The American Gastroenterological Association (AGA) developed this guideline to provide recommendations on the use of fecal microbiota-based therapies in adults with recurrent Clostridioides difficile infection; severe to fulminant C difficile infection; inflammatory bowel diseases, including pouchitis; and irritable bowel syndrome.

The guideline was developed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis. The guideline panel used the Evidence-to-Decision framework to develop recommendations for the use of fecal microbiota-based therapies in the specified gastrointestinal conditions and provided implementation considerations for clinical practice.

The guideline panel made 7 recommendations. In immunocompetent adults with recurrent C difficile infection, the AGA suggests select use of fecal microbiota-based therapies on completion of standard of care antibiotics to prevent recurrence. In mildly or moderately immunocompromised adults with recurrent C difficile infection, the AGA suggests select use of conventional fecal microbiota transplant. In severely immunocompromised adults, the AGA suggests against the use of any fecal microbiota-based therapies to prevent recurrent C difficile. In adults hospitalized with severe or fulminant C difficile not responding to standard of care antibiotics, the AGA suggests select use of conventional fecal microbiota transplant. The AGA suggests against the use of conventional fecal microbiota transplant as treatment for inflammatory bowel diseases or irritable bowel syndrome, except in the context of clinical trials.

Fecal microbiota-based therapies are effective therapy to prevent recurrent C difficile in select patients. Conventional fecal microbiota transplant is an adjuvant treatment for select adults hospitalized with severe or fulminant C difficile infection not responding to standard of care antibiotics. Fecal microbiota transplant cannot yet be recommended in other gastrointestinal conditions.

The microbial communities that inhabit our bodies have been increasingly linked to host physiology and pathophysiology. This microbiome, through its role in colonization resistance, influences the risk of infections after transplantation, including those caused by multidrug-resistant organisms. In addition, through both direct interactions with the host immune system and via the production of metabolites that impact local and systemic immunity, the microbiome plays an important role in the establishment of immune tolerance after transplantation, and conversely, in the development of graft-versus-host disease and graft rejection. This review offers a comprehensive overview of the evidence for the role of the microbiome in hematopoietic cell and solid organ transplant complications, drivers of microbiome shift during transplantation, and the potential of microbiome-based therapies to improve pediatric transplantation outcomes.

Clostridioides difficile (C. difficile) is a bacterial organism that typically infects the colon, which has had its homeostasis of healthy gut microbiota disrupted by antibiotics or other interventions. Patients with kidney transplantation are a group that are susceptible to C. difficile infection (CDI) and have poorer outcomes with CDI given that they conventionally require long-term immunosuppression to minimize their risk of graft rejection, weakening their responses to infection. Recognizing the risk factors and complex pathophysiological processes that exist between immunosuppression, dysbiosis, and CDI is important when making crucial clinical decisions surrounding the management of this vulnerable patient cohort. Despite the clinical importance of this topic, there are few studies that have evaluated CDI in the context of kidney transplant recipients and other solid organ transplant populations. The current recommendations on CDI management in kidney transplant and solid organ transplant recipients are mostly extrapolated from data relating to CDI management in the general population. We provide a narrative review that discusses the available evidence examining CDI in solid organ transplant recipients, with a particular focus on the kidney transplant recipient, from the epidemiology of CDI, clinical features and implications of CDI, potential risk factors of CDI, and, ultimately, prevention and management strategies for CDI, with the aim of providing areas for future research development in this topic area.

Research and innovation around Clostridium difficile infection (CDI) has been a multidisciplinary endeavor since discovery of the organism in 1978. The field of gastroenterology has contributed to our understanding of CDI as a disease caused by disruptions in the gut microbiome and led to advances in therapeutic manipulation of gut microbiota, including fecal microbiota transplantation. The high incidence of CDI in patients with inflammatory bowel disease and treatment of the infection in this population have been of particular interest to gastroenterologists. The emergence of standardized, approved live biotherapeutic products for treatment of recurrent CDI is an inflection point in our management of this difficult clinical problem, and real-world performance of these therapies will inform optimal treatment algorithms.

Multidrug-resistant organism (MDRO) colonization is a fundamental challenge in antimicrobial resistance. Limited studies have shown that fecal microbiota transplantation (FMT) can reduce MDRO colonization, but its mechanisms are poorly understood. We conducted a randomized, controlled trial of FMT for MDRO decolonization in renal transplant recipients called PREMIX (NCT02922816). Eleven participants were enrolled and randomized 1:1 to FMT or an observation period followed by delayed FMT if stool cultures were MDRO positive at day 36. Participants who were MDRO positive after one FMT were treated with a second FMT. At last visit, eight of nine patients who completed all treatments were MDRO culture negative. FMT-treated participants had longer time to recurrent MDRO infection versus PREMIX-eligible controls who were not treated with FMT. Key taxa (Akkermansia muciniphila, Alistipes putredinis, Phocaeicola dorei, Phascolarctobacterium faecium, Alistipes species, Mesosutterella massiliensis, Barnesiella intestinihominis, and Faecalibacterium prausnitzii) from the single feces donor used in the study that engrafted in recipients and metabolites such as short-chain fatty acids and bile acids in FMT-responding participants uncovered leads for rational microbiome therapeutic and diagnostic development. Metagenomic analyses revealed a previously unobserved mechanism of MDRO eradication by conspecific strain competition in an FMT-treated subset. Susceptible Enterobacterales strains that replaced baseline extended-spectrum β-lactamase-producing strains were not detectable in donor microbiota manufactured as FMT doses but in one case were detectable in the recipient before FMT. These data suggest that FMT may provide a path to exploit strain competition to reduce MDRO colonization.

The Antibacterial Resistance Leadership Group (ARLG) Mentoring Program was established to develop and prepare the next generation of clinician-scientists for a career in antibacterial resistance research. The ARLG Diversity, Equity, and Inclusion Working Group partners with the Mentoring Committee to help ensure diversity and excellence in the clinician-scientist workforce of the future. To advance the field of antibacterial research while fostering inclusion and diversity, the Mentoring Program has developed a number of fellowships, awards, and programs, which are described in detail in this article.

Background Clostridioides difficile infection (CDI) is a major cause of hospital-acquired diarrhea and is associated with substantial morbidity and mortality. Recurrences following treatment are common. Fecal microbiota transplantation (FMT) is a therapeutic intervention in which stool from a healthy donor is administered to a patient with recurrent CDI. Studies to date of predictors of FMT failure have primarily included inpatients. In this study, we aimed to describe FMT failure rates within one year of FMT and evaluate factors associated with FMT failure. Methodology We conducted an exploratory retrospective study of consecutive patients who underwent outpatient FMT at a single tertiary care center in Western Massachusetts from December 2014 through September 2018. We collected patient data including demographics, CDI-related factors, and FMT-related factors. FMT failure was defined as non-response or recurrence of diarrhea, associated with positive stool C. difficile toxin or polymerase chain reaction. Unadjusted relative risk (RR) and 95% confidence intervals for factors associated with FMT failure were estimated using log-binomial regression. Results A total of 92 patients were included with a mean age of 64 years. CDI severity was mild or moderate in 73% and severe or fulminant in 27%. The most common FMT indication was recurrent CDI in 76% of patients. FMT failure occurred in 25 of 92 (27%) patients, with half occurring within 11 days. Factors associated with FMT failure were active malignancy (RR = 2.56), prior hospitalizations (RR = 2.42), and receipt of non-CDI antibiotics within six months of FMT (RR = 2.80). We did not observe strong associations for risk of FMT failure with age ≥65, sex, use of proton pump inhibitors or H2 receptor agonists, history of colectomy, immunosuppression, history of malignancy, diabetes, appendectomy, CDI severity, or probiotic use. Conclusions Active malignancy, prior CDI hospitalizations, and non-CDI antibiotics within six months before FMT were associated with FMT failure in the outpatient setting. Knowledge of the above factors may help inform shared decision-making with patients at risk for FMT failure.

Fecal microbiota transplant (FMT) is an effective treatment for recurrent Clostridioides difficile infection (CDI). Safety concerns around FMT are increased in immunocompromised populations, such as solid organ transplant (SOT) recipients. Outcomes among adult SOT recipients suggest FMT is efficacious and safe; however, pediatric SOT data are lacking.

We describe the efficacy and safety of FMT among pediatric SOT recipients in a single-center retrospective study from March 2016 to December 2019. Successful FMT was defined as no recurrence of CDI within 2 mo of FMT. We identified 6 SOT recipients ages 4-18 y who received FMT a median of 5.3 y post-SOT.

Success after a single FMT was 83.3%. One liver recipient did not achieve cure after 3 FMTs and remains on low-dose vancomycin. One serious adverse event (SAE) occurred; cecal perforation and bacterial peritonitis occurred following colonoscopic FMT coordinated with intestinal biopsy in a kidney transplant recipient. He achieved full recovery and CDI cure. There were no other SAEs. There were no adverse events related to immunosuppression or transplantation status including: bacteremia, cytomegalovirus activation or reactivation, allograft rejection, or allograft loss.

In this limited series, efficacy of FMT in pediatric SOT is comparable to efficacy in the general pediatric recurrent CDI population. There may be an increased risk of procedure-related SAE in SOT patients and larger cohort studies are needed.

Recently the role of gut microbial dysbiosis in many ocular disorders, including but not limited to uveitis, age-related macular degeneration (AMD), diabetic retinopathy (DR), dry eye, keratitis and orbitopathy is a hot research topic in the field. Targeting gut microbiota to treat these diseases has become an unstoppable trend. Bibliometric study and visualization analysis have become essential methods for literature analysis in the medical research field. We aim to depict this area's research hotspots and future directions by bibliometric software and methods.

We search all the related publications from the Web of Science Core Collection. Then, CiteSpace was applied to analyze and visualize the country distributions, dual-map overlay of journals, keyword bursts, and co-cited references. VOSviewer was employed to identify authors, co-cited authors, journals and co-cited journals and display the keyword co-occurrence networks.

A total of 284 relevant publications were identified from 2009 to 2023. The number of studies has been small in the first five years and has grown steadily since 2016. These studies were completed by 1,376 authors from 41 countries worldwide, with the United States in the lead. Lin P has published the most papers while Horai R is the most co-cited author. The top journal and co-cited journal are both Investigative Ophthalmology & Visual Science. In the keyword co-occurrence network, except gut microbiota, inflammation becomes the keyword with the highest frequency. Co-citation analyses reveal that gut dysbiosis is involved in common immune- and inflammation-mediated eye diseases, including uveitis, diabetic retinopathy, age-related macular degeneration, dry eye, and Graves' orbitopathy, and the study of microbiomes is no longer limited to the bacterial populations. Therapeutic strategies that target the gut microbiota, such as probiotics, healthy diet patterns, and fecal microbial transplantation, are effective and critical to future research.

In conclusion, the bibliometric analysis displays the research hotspots and developmental directions of the involvement of gut microbiota in the pathogenesis and treatment of some ocular diseases. It provides an overview of this field's dynamic evolution and structural relationships.

Clostridioides difficile infection (CDI) is a major healthcare problem in the developed world, and effective management of recurrent infection remains one of the biggest challenges. Several advances have occurred in the management of CDI, and in the last 15 years, multiple new agents have been tested. Since 2011, four new products have been approved by the US FDA for treatment of CDI or prevention of recurrent CDI.

This review focuses on therapeutics of CDI and includes sections on primary prevention, management of active infection, and prevention of recurrent CDI. Specifically, data are included on fecal microbiota transplantation and live biotherapeutics. A comprehensive search of several databases including Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from inception to 1 May 2023 was conducted.

Metronidazole is no longer advised for management of outpatient CDI. The preferred medication of choice for a first episode is oral vancomycin or fidaxomicin. For those patients who recur after the first episode, vancomycin taper pulse or fidaxomicin can be used. Intravenous bezlotoxumab, a monoclonal antibody, is available to prevent recurrences. There are now two FDA-approved microbiome-based therapies or live biotherapeutics for prevention of recurrent CDI, for any recurrent CDI and not necessarily multiply recurrent C difficile. Fecal microbiota transplantation remains available in limited settings for recurrent CDI.

Up to 35% of patients with a first episode of Clostridioides difficile infection (CDI) develop recurrent CDI (rCDI), and of those, up to 65% experience multiple recurrences. A systematic literature review (SLR) was conducted to review and summarize the economic impact of rCDI in the United States of America.

English-language publications reporting real-world healthcare resource utilization (HRU) and/or direct medical costs associated with rCDI in the USA were searched in MEDLINE, MEDLINE In-Process, Embase, and the Cochrane Library databases over the past 10 years (2012-2022), as well as in selected scientific conferences that publish research on rCDI and its economic burden over the past 3 years (2019-2022). HRU and costs identified through the SLR were synthesized to estimate annual rCDI-attributable direct medical costs to inform the economic impact of rCDI from a US third-party payer's perspective.

A total of 661 publications were retrieved, and 31 of them met all selection criteria. Substantial variability was found across these publications in terms of data source, patient population, sample size, definition of rCDI, follow-up period, outcomes reported, analytic approach, and methods to adjudicate rCDI-attributable costs. Only one study reported rCDI-attributable costs over 12 months. Synthesizing across the relevant publications using a component-based cost approach, the per-patient per-year rCDI-attributable direct medical cost was estimated to range from $67,837 to $82,268.

While real-world studies on economic impact of rCDI in the USA suggested a high-cost burden, inconsistency in methodologies and results reporting warranted a component-based cost synthesis approach to estimate the annual medical cost burden of rCDI. Utilizing available literature, we estimated the average annual rCDI-attributable medical costs to allow for consistent economic assessments of rCDI and identify the budget impact on US payers.

Cronh's disease and ulcerative colitis (UC) are diseases with unknown etiologies that cause ongoing inflammation in the gastrointestinal system. Chron's disease causes immunological dysregulation, and UC causes intestinal harm due to immune reactions. According to our study, fecal microbiota transplantation (FMT) has many benefits in the treatment of inflammatory bowel disease (IBD) by restoring intestinal homeostasis and reducing clinical symptoms. In mildly symptomatic patients with UC, an FMT treatment combined with an anti-inflammatory diet can produce remission, which would then be followed by a diet that maintained the anti-inflammatory effects. The efficacy of FMT consists of preventing flares or the consequences of IBD. As a result, we must emphasize that more investigation should be done before developing a therapeutic procedure for FMT in IBD and its associated consequences.

Organ transplantation has provided another chance of survival for end-stage organ failure patients. Yet, transplant rejection is still a main challenging factor. Immunosuppressive drugs have been used to avoid rejection and suppress the immune response against allografts. Thus, immunosuppressants increase the risk of infection in immunocompromised organ transplant recipients. The infection risk reflects the relationship between the nature and severity of immunosuppression and infectious diseases. Furthermore, immunosuppressants show an immunological impact on the genetics of innate and adaptive immune responses. This effect usually reactivates the post-transplant infection in the donor and recipient tissues since T-cell activation has a substantial role in allograft rejection. Meanwhile, different infections have been found to activate the T-cells into CD₄⁺ helper T-cell subset and CD₈⁺ cytotoxic T-lymphocyte that affect the infection and the allograft. Therefore, the best management and preventive strategies of immunosuppression, antimicrobial prophylaxis, and intensive medical care are required for successful organ transplantation. This review addresses the activation of immune responses against different infections in immunocompromised individuals after organ transplantation.

We sought to evaluate the safety and effectiveness of fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) in pediatric immunocompromised (IC) patients.

This is a multicenter retrospective cohort study of pediatric participants who underwent FMT between March 2013 and April 2020 with 12-week follow-up. Pediatric patients were included if they met the definition of IC and were treated with FMT for an indication of recurrent CDI. We excluded patients over 18 years of age, those with incomplete records, insufficient follow-up, or not meeting study definition of IC. We also excluded those treated for Clostridioides difficile recurrence without meeting the study definition and those with inflammatory bowel disease without another immunocompromising condition.

Of 59 pediatric patients identified at 9 centers, there were 42 who met inclusion and no exclusion criteria. Included patients had a median age of 6.7 years. Etiology of IC included: solid organ transplantation (18, 43%), malignancy (12, 28%), primary immunodeficiency (10, 24%), or other chronic conditions (2, 5%). Success rate was 79% after first FMT and 86% after 1 or more FMT. There were no statistically significant differences in patient characteristics or procedural components when patients with a failed FMT were compared to those with a successful FMT. There were 15 total serious adverse events (SAEs) in 13 out of 42 (31%) patients that occurred during the follow-up period; 4 (9.5%) of which were likely treatment-related. There were no deaths or infections with multidrug resistant organisms during follow-up and all patients with a SAE fully recovered.

The success rate of FMT for recurrent CDI in this pediatric IC cohort is high and mirrors data for IC adults and immunocompetent children. FMT-related SAEs do occur (9.5%) and highlight the need for careful consideration of risk and benefit.

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent/refractory Clostridioides difficile infection (CDI) with a 10% to 20% risk of recurrence after a single FMT. In this meta-analysis, we aimed to evaluate the predictors of FMT failure.

A comprehensive search of MEDLINE, Embase, Cochrane, and Web of Science databases through July 2021 was performed. All studies that evaluated risk factors associated with FMT failure in a multivariate model were included. We calculated pooled odds ratios with 95% confidence intervals for risk factors reported in ≥3 studies using a random-effects model.

Twenty studies involving 4327 patients (63.6% females) with recurrent/refractory CDI who underwent FMT were included. FMT failed in 705 patients (16.3%) with 2 to 3 months of follow-up in most studies. A total of 12 different risk factors were reported in a multivariate model in ≥3 studies. Meta-analysis showed that advanced age, severe CDI, inflammatory bowel disease, peri-FMT use of non-CDI antibiotics, prior CDI-related hospitalizations, inpatient status, and poor quality of bowel preparation were significant predictors of FMT failure. Charlson Comorbidity Index, female gender, immunosuppressed status, patient-directed donor, and number of CDI recurrences were not associated with FMT failure.

Adequate bowel preparation at the time of FMT and optimizing antibiotic stewardship practices in the peri-FMT period can improve the success of FMT. Patients with nonmodifiable risk factors should be counseled about the risk of FMT failure. Our results may help develop a risk stratification model to predict FMT failure in CDI patients.

Despite significant advances in therapies, heart failure (HF) remains a progressive disease that, once advanced, is associated with significant death and disability. Cardiac replacement therapies with left ventricular assist device (LVAD) and heart transplantation (HT) are the only treatment options for advanced HF, while lifesaving they can also be lifespan limiting due to the associated complications. Systemic inflammation is mechanistically important in HF pathophysiology and progression. However, directly targeting inflammation in HF has not been beneficial thus far. These failed attempts at therapeutics might be related to our limited understanding of the factors that cause inflammation in HF, and, therefore, to our inability to investigate these triggers in interventional studies. Observational studies have consistently demonstrated associations between alterations in the digestive (gut and oral) microbiome, inflammation and HF risk and progression. Additionally, recent data indicate that these microbial perturbations persist following LVAD and HT, along with residual inflammation and oxidative stress. Furthermore, there is rising recognition of the critical contribution of the microbiome to the metabolism of immunosuppressive drugs after HT. Cumulatively, these findings might posit a mechanistic link between microbiome alterations, systemic inflammation, and adverse outcomes in HF patients before and after cardiac replacement therapies. This review (1) provides an update on available data linking changes in digestive tract microbiota, inflammation, and oxidative stress, to HF pathogenesis and progression; (2) describes evolution of these relationships following LVAD and HT; and (3) outlines present and future intervention strategies that can manipulate the microbiome and possibly modify HF disease trajectory.

Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea in the United States. We aimed to determine comparative trends in inpatient outcomes of liver transplant (LT) patients based on CDI during hospitalizations.

The national inpatient sample database was used to conduct the present retrospective study regarding CDI among the LT hospitalizations from 2009 to 2019. Primary outcomes included 10-year comparative trends of the length of stay (LOS) and mean inpatient charges (MIC). Secondary outcomes included comparative mortality and LT rejection trends.

There was a 14.05% decrease in CDI in LT hospitalizations over the study period (p = .05). The trend in LOS did not significantly vary (p = .9). MIC increased significantly over the last decade in LT hospitalizations with CDI (p < .001). LT hospitalizations of autoimmune etiology compared against non-autoimmune did not increase association with CDI, adjusted odds ratio (aOR) 0.97 (95% confidence interval [CI] 0.75-1.26, p = .87). CDI was associated with increased mortality in LT hospitalizations, aOR 1.84 (95% CI 1.52-2.24, p < .001). In-hospital mortality for LT hospitalizations with CDI decreased by 7.75% over the study period (p = .3). CDI increased transplant rejections, aOR 1.3 (95% CI 1.08-1.65, p < .001). There was a declining trend in transplant rejection for LT hospitalization with CDI from 5% to 3% over the study period (p = .0048).

CDI prevalence does not increase based on autoimmune LT etiology. It increases mortality in LT hospitalizations; however, trend for mortality and transplant rejections has been declining over the last decade.

Immunocompromised patients are particularly vulnerable to Clostridioides difficile infection (CDI), hospitalizations and recurrences. Studies have shown that fecal microbiota transplant (FMT) is safe and effective in immunocompromised patients.

To examine the outcomes of FMT for CDI in a diverse cohort of immunocompromised patients stratified by medication class.

We performed a retrospective, long-term follow-up study of FMT in immunocompromised patients, including those undergoing chemotherapy, with inflammatory bowel disease (IBD) on immunomodulators, prior solid organ transplant on immunosuppressants, on chronic steroids 20 mg/day or higher for a minimum of three months, or HIV positive. Primary outcomes included adjusted primary cure rate within 8 weeks, as well as rates of non-response, recurrences, relapses and adverse events. Secondary outcomes included adjusted overall cure rate. Primary cure rate was defined as patients not requiring repeat CDI treatment within 8 weeks after index FMT, and overall cure rate was defined as resolution of CDI symptoms after index FMT or second FMT.

Our cohort included 77 immunosuppressed patients (53.2% female, median age 39.1 years, range 7-95 years). The majority of our cohort were IBD patients on biologics (62.3%). Adjusting for colectomies and deaths, our primary and overall cure rates were 85.1% and 86.5%, respectively. Twelve patients received FMT for severe or fulminant CDI with a 3-month survival rate of 91.7%. 11.7% of patients experienced serious adverse events following FMT.

Our study supports the efficacy and safety of FMT in immunocompromised patients, though future research is needed to further ascertain the potential effects of immunosuppression on FMT outcomes.

More than 95 % of human diseases may be related to the disturbance of gut microbes. As a treatment method that extensively regulates the gut microbes, fecal microbiota transplantation (FMT) has proven to be an effective therapy for some diseases, becoming a topic of interest among clinicians, patients and scientists.

To review the latest clinical research results of FMT in the treatment of various diseases and the methodology and risk management in clinical application.

Search PubMed and Web of Science for reliable research results of clinical treatment of FMT within 5-10 years, as well as application guidelines and risk management policies in different regions.

As a measure of allogeneic/autologous microbiota transplantation, FMT has been used to treat a variety of diseases. By reviewing the clinical studies of FMT in gastrointestinal diseases, metabolic diseases, neurological diseases and malignant tumors, the various mechanisms in the treatment of diseases are summarized. Such as regulation of receptor microbiota composition, specific metabolites, phage function and immune response. In addition, potential risk factors, donor stool screening indicators, recipient self-specificity and possible prognostic marker molecules in the course of FMT treatment were generalized.

The potential regulatory mechanisms, risk factors and targets of FMT in gastrointestinal diseases, metabolic diseases, malignancies and neurological diseases were reviewed and proposed. It provides a theoretical basis for the establishment of a standardized treatment system for FMT and a breakthrough in treatment technology.

Fecal microbiota transplantation (FMT) has been used as a core therapy for treating dysbiosis-related diseases by remodeling gut microbiota. The methodology and technology for improving FMT are stepping forward, mainly including washed microbiota transplantation (WMT), colonic transendoscopic enteral tubing (TET) for microbiota delivery, and purified Firmicutes spores from fecal matter. To improve the understanding of the clinical applications of FMT, we performed a systematic literature review on FMT published from 2011 to 2021. Here, we provided an overview of the reported clinical benefits of FMT, the methodology of processing FMT, the strategy of using FMT, and the regulations on FMT from a global perspective. A total of 782 studies were included for the final analysis. The present review profiled the effectiveness from all clinical FMT uses in 85 specific diseases as eight categories, including infections, gut diseases, microbiota-gut-liver axis, microbiota-gut-brain axis, metabolic diseases, oncology, hematological diseases, and other diseases. Although many further controlled trials will be needed, the dramatic increasing reports have shown the promising future of FMT for dysbiosis-related diseases in the gut or beyond the gut.