Search

The gut microbiota is considered a key component in many aspects of cancer pathophysiology and response to therapy. In particular, in recent years intriguing evidences has been emerging regarding the role of the intestinal microbiota in the response to immunotherapy and in promoting the development of adverse events, such as colitis. For this reason, studies are being carried out both on pre-clinical models and on humans to study how to predict the response to immunotherapy through the study of the microbiota or how to improve its clinical response through modulation. Promising data have recently been reported through modulation by probiotics or prebiotics, and in particular by fecal microbiota transplantation. The aim of this review is to analyze the evidence regarding the role of the microbiota in immunotherapy with a particular focus on melanoma.

Background Increasing evidence supports the role of the gut microbiota in the aetiology of irritable bowel syndrome (IBS). Faecal microbiota transplantation (FMT) is a highly effective treatment against recurrent Clostridioides difficile infection in randomised controlled trials (RCTs), and may be beneficial in ulcerative colitis. However, its efficacy in IBS is uncertain. Aim To perform a systematic review and meta-analysis to examine this issue. Methods We searched MEDLINE, EMBASE, EMBASE Classic, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov through to March 2019. RCTs recruiting adults with IBS, which compared FMT with placebo, were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% CI. Results The search strategy identified 322 citations. Five RCTs were eligible for inclusion, containing 267 patients. Overall, 92.2% of included patients had IBS-D or IBS-M, and only 7.8% IBS-C. When data were pooled for all patients, irrespective of stool type, the RR of IBS symptoms not improving was 0.98 (95% CI 0.58-1.66). Placebo capsules administered orally were superior to capsules containing donor stool in two pooled trials (RR = 1.96; 95% CI 1.19-3.20). FMT from donor stool delivered via colonoscopy was superior to autologous stool in two pooled RCTs (RR = 0.63; 95% CI 0.43-0.93). FMT from donor stool via nasojejunal tube showed a trend towards a benefit over autologous stool in one trial (RR = 0.69; 95% CI 0.46-1.02). Conclusions Fresh or frozen donor stool delivered via colonoscopy or nasojejunal tube may be beneficial in IBS. Larger, more rigorously conducted trials of FMT in IBS are needed.

Recurrent cystitis (RC) is a common disease, especially in females. Anatomical, behavioral and genetic predisposing factors are associated with the ascending retrograde route, which often causes bladder infections. RC seems to be mainly caused by agents derived from the intestinal microbiota, and most frequently by Escherichia coli. Intestinal contiguity contributes to the etiopathogenesis of RC and an alteration in intestinal permeability could have a major role in RC. The aim of this pilot study is to assess gut microbiome dysbiosis and intestinal permeability in female patients with RC. Patients with RC (n = 16) were enrolled and compared with healthy female subjects (n = 15) and patients with chronic gastrointestinal (GI) disorders (n = 238). We calculated the Acute Cystitis Symptom Score/Urinary Tract Infection Symptom Assessment (ACSS/UTISA) and Gastrointestinal Symptom Rating Scale (GSRS) scores and evaluated intestinal permeability and the fecal microbiome in the first two cohorts. Patients with RC showed an increased prevalence of gastrointestinal symptoms compared with healthy controls. Of the patients with RC, 88% showed an increased intestinal permeability with reduced biodiversity of gut microbiota compared to healthy controls, and 68% of the RC patients had a final diagnosis of gastrointestinal disease. Similarly, GI patients reported a higher incidence of urinary symptoms with a diagnosis of RC in 20%. Gut barrier impairment seems to play a major role in the pathogenesis of RC. Further studies are necessary to elucidate the role of microbiota and intestinal permeability in urinary tract infections.

Background Severe or fulminant Clostridioides difficile infection (SFCDI) is associated with significant morbidity and mortality. Emerging evidence suggests fecal microbiota transplant (FMT) may be a promising therapy for SFCDI. Aim This systematic review determines the safety and efficacy of FMT in medically refractory SFCDI. Methods A systematic search of the literature was conducted using PubMed (1965 to 2020), Web of Science (1900 to 20), EMBASE (1974 to 2020), and Cochrane Review (1945 to 2020). Quality appraisal by NIH Study Quality Assessment tools, and data extraction were performed by two teams of independent researchers. The primary outcome was resolution of SFCDI 4 weeks after the final FMT. Pooled resolution rates were calculated using generalized linear mixed models estimates. Results Two hundred and forty patients from 10 studies (8 case series, 1 case–control and 1 randomized study) were included with 209 individual patient-level data. FMT resulted in resolution of SFCDI within 4 weeks in 211/240 individuals for a pooled estimate of 88% (95% confidence interval [CI]: 0.83 to 0.91). The mean number of FMT required was 1.6 for severe and 2.0 for fulminant CDI resolution. The pooled proportional estimates for patients requiring CDI-directed antimicrobials after FMT was 50% (95% CI: 0.06 to 0.94) for severe CDI and 67.0% (95% CI: 0.30 to 0.91) for fulminant CDI. Serious adverse event rates were low. Conclusion FMT appears effective in treating SFCDI patients with low adverse events, but requires multiple treatments with a significant proportion of patients requiring additional anti-CDI antibiotics to achieve resolution. The optimal route of FMT delivery remains unknown. The presence of pseudomembranous colitis may guide additional FMT or anti-CDI antibiotic treatment.

International audience

Background The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) has a tropism for the gastrointestinal tract and several studies have shown an alteration of the gut microbiota in hospitalized infected patients. However, long-term data on microbiota changes after recovery are lacking. Methods We enrolled 30 patients hospitalized for SARS‑CoV‑2-related pneumonia. Their gut microbiota was analyzed within 48 h from the admission and compared with (1) that of other patients admitted for suspected bacterial pneumonia (control group) (2) that obtained from the same subject 6 months after nasopharyngeal swab negativization. Results Gut microbiota alpha-diversity increased 6 months after the resolution of SARS-CoV-2 infection. Bacteroidetes relative abundance was higher (≈ 36.8%) in patients with SARS-CoV-2, and declined to 18.7% when SARS-CoV-2 infection resolved (p = 0.004). Conversely, Firmicutes were prevalent (≈ 75%) in controls and in samples collected after SARS-CoV-2 infection resolution (p = 0.001). Ruminococcaceae, Lachnospiraceae and Blautia increased after SARS-CoV-2 infection resolution, rebalancing the gut microbiota composition. Conclusion SARS-CoV-2 infection is associated with changes in the gut microbiome, which tend to be reversed in long-term period.

Inflammatory bowel disease (IBD) is a risk factor for C. difficile infection (CDI), which, in turn, complicates the clinical course of IBD. Fecal microbiota transplantation (FMT) is safe and effective in patients with IBD and recurrent CDI (rCDI). In our study, patients with IBD and rCDI received FMT by colonoscopy and were followed-up for 8 weeks. The primary outcome was negative C. difficile toxin 8 weeks after FMT. Eighteen patients with IBD were enrolled. Eight patients received sequential FMT either for pseudomembranous colitis or failure of single fecal infusion. At 8-week follow-up the C. difficile toxin was negative in 17 patients, and most (83%) experienced also improvement of IBD disease activity. Overall, we did not observe any serious adverse event. FMT appears to be highly effective and safe in patients with IBD and rCDI and is likely not only to eradicate CDI but also to improve disease activity of IBD.

Background Due to the increasing rise of C. difficile infection, stool banks and donor programs have been launched to grant access to fecal microbiota transplantation (FMT). Our aim is to describe characteristics and outcomes of the donor program at our stool bank. Methods Donor candidates underwent a four-step selection process, including a clinical interview, blood and stool testing, a further questionnaire and a direct stool testing the day of each donation. From March 2020, specific changes to this process were introduced to avoid the potential transmission of COVID-19. We evaluated the rate of excluded candidates at each step of the screening, as well as the number of total fecal aliquots provided by qualified donors. Results Overall, 114 donor candidates were evaluated. Seventy-five candidates declined to join the program for logistic or personal issues, three were excluded after the questionnaire and seven for positive stool exams. Finally, 29 (25%) subjects qualified as stool donors, and provided 70 stool samples. Fifteen samples were excluded after direct molecular stool testing. A total of 127 aliquots was finally obtained. Conclusions Donor recruitment for FMT is a challenging process, and only a small rate of candidates are eligible as donors.

The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.

The micro-organisms residing within the gastrointestinal tract, namely gut microbiota, form a dynamic population proper of each individual, mostly composed by bacteria which co-evolved symbiotically with human species. The advances of culture-independent techniques allowed the understanding of the multiple functions of the gut microbiota in human physiology and disease, the latter often recognising a predisposing condition in an imbalanced intestinal microbial ecosystem (dysbiosis). A complex mutual interconnection between the central nervous system (CNS), the intestine and the gut microbiota, known as "microbiota-gut-brain axis", has been hypothesized to play a pivotal role in maintaining central and peripheral functions, as well as mental health. Thus, dysbiosis with specific microbiota imbalances seems to be strongly associated with the onset psychiatric disorders by altering neurodevelopment, enhancing neurodegeneration, affecting behaviour and mood. Fecal microbiota transplantation (FMT) consists of transferring the fecal matter from a donor into the gastrointestinal tract of a recipient, and it is used to quickly modulate the gut microbiota. This review focuses on the uses of FMT in psychiatric disorders. FMT has been used to induce dysbiosis and to study the disease development, or to heal dysbiosis-related mental disorders. Overall, FMT of impaired microbiota resulted effective in enhancing psychiatric-like disturbances (mainly depression and anxiety) in recipient animals, plausibly by impairing immune system, inflammatory and metabolic pathways, neurochemical processes and neuro-transmission. On the other side, preclinical and clinical data suggest that reversing or mitigating dysbiosis seems a promising strategy to restore behavioural impairments or to obtain psychiatric symptom relief. However, current evidence is limited by the lack of procedural standardization, the paucity of human studies in the vastity of psychiatric conditions and the need of a microbiota-targeted donor-recipient matching.

Faecal microbiota transplantation (FMT) is an effective treatment in C. difficile infection (CDI) and is currently being investigated in other diseases. There is concern around the safety of FMT and that side effects or complications may be under-reported in the medical literature.To evaluate the safety of FMT by summarising the overall reported Adverse Events (AEs) over a 20-year period METHODS: We searched EMBASE, MEDLINE, and Cochrane Library databases, and CNKI and Wanfang Data from January 2000 to April 2020. All original studies reporting FMT-related AEs were considered for inclusion. FMT-related AEs were further classified as delivery-related or microbiota-related.Based on the inclusion criteria, 129 studies, which included 4241 patients (5688 FMT courses), were finally eligible. The most common indication for FMT was CDI. Overall, FMT-related AEs were observed in 19% of FMT procedures. The most frequently reported FMT-related AEs were diarrhoea (10%) and abdominal discomfort/pain/cramping (7%). FMT-related serious adverse events (SAEs), including infections and deaths, have been reported in 1.4% of patients who underwent FMT (0.99% microbiota-related SAEs). Four of five FMT-related deaths were reported in patients receiving FMT via the upper gastrointestinal route. Importantly, all reported FMT-related SAEs were in patients with mucosal barrier injury.Most FMT-related AEs were mild or moderate and self-limiting. Although FMT appears to be highly safe, its methodology should be improved to reduce both delivery-related AEs and, microbiota-related AEs.

Background and study aims The COVID-19 pandemic is having a major clinical and also organizational impact on national health care systems, particularly in high-volume hospitals that are utilized for several essential clinical needs. We aimed to analyze the short-term impact of the SARS-CoV-2 pandemic on management of endoscopic procedures in patients with inflammatory bowel disease (IBD). Patients and methods This was an observational prospective study exploring major clinical and organizational changes in endoscopic management at the IBD Center – CEMAD of the Fondazione Policlinico Gemelli IRCCS, Rome, Italy since the beginning of SARS-CoV-2 pandemic. Results Our IBD Unit, with up to 1,500 IBD patients receiving biotechnological or experimental therapy, represents a high-volume Italian and European IBD center. Since the beginning of the outbreak, our hospital has been extremely impacted by care related to COVID-19 cases, with a consequent need to dramatically reorganize management of endoscopic procedures for IBD. Conclusions Outbreak restrictions have significantly impacted the volume of endoscopic activities for IBD. Specific strategies have been designed to guarantee a high level of safety for both patients with IBD and healthcare personnel dedicated to their treatment.

The standard conditions of critical illness (including sepsis, acute respiratory distress syndrome, and multiorgan failure) cause enormous global mortality and a growing economic burden. Increasing evidence suggests that critical illness may be associated with loss of commensal microbes and overgrowth of potentially pathogenic and inflammatory bacteria. This state could be associated with poor outcomes. Therefore, microbiota-targeted interventions are potentially attractive novel treatment options. Although the precise mechanisms of microbiome-directed treatments such as prebiotics, probiotics, and fecal microbiota transplantation remain to be determined, they can be utilized in the Intensive Care Unit (ICU) setting. The current review aims to offer intensivists an evidenced-based approach on what we currently know about the role of the microbiome in critical illness and how the microbiome could be targeted in the clinical practice to improve ICU-related outcomes.

Although long thought to be a sterile and inhospitable environment, the stomach is inhabited by diverse microbial communities, co-existing in a dynamic balance. Long-term use of orally administered drugs such as Proton Pump Inhibitors (PPIs), or bacterial infection such as Helicobacter pylori, cause significant microbial alterations. Yet, studies revealing how the commensal bacteria re-organize, due to these perturbations of the gastric environment, are in the early phase. They mainly focus on the most prevalent taxa and rely on linear techniques for multivariate analysis.Here we disclose the importance of complementing linear dimensionality reduction techniques such as Principal Component Analysis and Multidimensional Scaling with nonlinear approaches derived from the physics of complex systems. Then, we show the importance to complete multivariate pattern analysis with differential network analysis, to reveal mechanisms of re-organizations which emerge from combinatorial microbial variations induced by a medical treatment (PPIs) or an infectious state (H. pylori).

International audience

Introduction: Established evidence suggests that gut microbiota plays a role in ulcerative colitis (UC). Fecal microbiota transplantation (FMT) is clearly recognized as a highly effective treatment...

BACKGROUND: Fecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of feces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council.OBJECTIVE: Several European and international consensus statements concerning fecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document.METHODS: Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about fecal microbiota transplantation.RESULTS: A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening.CONCLUSION: The implementation of fecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor feces preparations for patients.

Diarrhoea is one of the most burdensome and common adverse events of chemotherapeutics, and has no standardised therapy to date. Increasing evidence suggests that the gut microbiome can influence the development of chemotherapy-induced diarrhoea. Here we report findings from a randomised clinical trial of faecal microbiota transplantation (FMT) to treat diarrhoea induced by tyrosine kinase inhibitors (TKI) in patients with metastatic renal cell carcinoma (ClinicalTrials.gov number: NCT04040712). The primary outcome is the resolution of diarrhoea four weeks after the end of treatments. Twenty patients are randomised to receive FMT from healthy donors or placebo FMT (vehicle only). Donor FMT is more effective than placebo FMT in treating TKI-induced diarrhoea, and a successful engraftment is observed in subjects receiving donor faeces. No serious adverse events are observed in both treatment arms. The trial meets pre-specified endpoints. Our findings suggest that the therapeutic manipulation of gut microbiota may become a promising treatment option to manage TKI-dependent diarrhoea., Tyrosine kinase inhibitors (TKIs) have improved the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC), however TKI-related diarrhoea is a common and serious adverse effect. Here the authors show in a randomized clinical trial that faecal microbiota transplantation from healthy donors can improve TKI-induced diarrhoea in patients with mRCC.

Background Gut microbiota exerts a crucial role in gastrointestinal (GI) and extra-intestinal (EI) disorders. In this context, Akkermansia muciniphila is pivotal for the maintenance of host health and has been correlated with several disorders. Aim To explore the potential role of A. muciniphila as common dysbiotic marker linked to the disease status. Methods A cohort of patients affected by GI and EI disorders was enrolled and compared to healthy controls (CTRLs). A targeted-metagenomics approach combined to unsupervised cluster and machine learning (ML) analyses provided microbiota signatures. Results Microbiota composition was associated to disease phenotype, therapies, diet and anthropometric features, identifying phenotype and therapies as the most impacting variables on microbiota ecology. Unsupervised cluster analyses identified one cluster composed by the majority of patients. DESeq2 algorithm identified ten microbial discriminatory features of patients and CTRLs clusters. Among these microbes, Akkermansia muciniphila resulted the discriminating ML node between patients and CTRLs, independently of specific GI/EI disease or confounding effects. A. muciniphila decrease represented a transversal signature of gut microbiota alteration, showing also an inverse correlation with α-diversity. Conclusion Overall, A. muciniphila decline may have a crucial role in affecting microbial ecology and in discriminating patients from healthy subjects. Its grading may be considered as a gut dysbiosis feature associated to disease-related microbiota profile.

Preliminary studies suggested a possible correlation of microbiota with Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), where the need for tools to ameliorate its poor prognosis is mandatory. We explored the potential signature of esophageal microbiota and its predicted functional profile along the continuous spectrum from BE to EAC. We analyzed through 16S-based amplicon sequencing the mucosal microbiota and the microbiota-related functional predictions in 10 BE and 6 EAC patients compared with 10 controls, exploring also potential differences between the metaplastic mucosa (BEM) and the adjacent normal areas of BE patients (BEU). BEM and EAC showed a higher level of alpha and beta-diversity. BEM evidenced a decrease of Streptococcus and an increase of Prevotella, Actinobacillus, Veillonella, and Leptotrichia. EAC displayed a striking reduction of Streptococcus, with an increase of Prevotella, Veillonella and Leptotrichia. LefSe analysis identified Leptotrichia as the main taxa distinguishing EAC. BEM showed a decreased a-diversity compared with BEU and a reduction of Bacteroidetes, Prevotella and Fusobacterium. Functional predictions identified peculiar profiles for each group with a high potential for replication and repair in BEM; an upregulated energy, replication and signaling metabolisms, with the fatty-acids biosynthesis and nitrogen and D-alanine pathways down-regulated in EAC. Our pilot study identifies a unique microbial structure and function profile for BE and EAC, as well as for metaplastic and near-normal areas. It proposes a new concept for BE, which could be intended not only as the histological, but, also, as the microbial closest precursor of EAC. This requires further larger follow-up studies, but opens intriguing horizons towards innovative diagnostic and therapeutic options for EAC.

Background and Aim: Fecal microbiota transplantation (FMT) has proven to be very effective in recurrent Clostridium difficile infection (CDI) when compared with standard antibiotic therapy. However, given the lack of validated criteria, decision regarding number and timing of infusions is currently based on the clinician's experience, severity of infection, and clinical response. We performed a longitudinal assessment of fecal calprotectin concentration (FCC) in CDI patients undergoing FMT. FCCs were correlated with the need for multiple infusions and with the clinical status of the patient. Methods: Fecal calprotectin concentration measurement was performed just before first procedure (T0) and 2 (T1) and 5 (T2) days later. The need for reinfusion was accounted for in the 8 weeks following procedure, and clinical status was evaluated at the end of the given period. Both outcomes were correlated with measured FCCs. Results: A total of 28 CDI patients undergoing FMT were enrolled. Median FCCs at T0 were significantly higher in patients who needed repeat FMT, 540 μg/g versus patients who underwent single FMT, 290 μg/g (P

Compositional and functional alterations of the gut microbiota are involved in the pathogenesis of several gastrointestinal diseases. Rifaximin is often used to induce disease remission due to its eubiotic effects on the gut microbiota. To investigate the correlation between changes in the gut microbiota composition and symptoms improvement in patients who present a clinical response to rifaximin treatment. Patients with ulcerative colitis (UC), Crohn’s disease (CD), irritable bowel syndrome (IBS) and diverticular disease (DD) undergoing rifaximin treatment for clinical indication were enrolled in the study. Rifaximin was administered at the dose of 1,200 mg/day for 10 days. Faecal samples were collected at baseline and at the end of treatment; clinical improvement was assessed by Mayo score for UC, CD Activity Index (CDAI) for CD, IBS severity scoring system (IBS-SSS) for IBS and global symptomatic score (GSS) for DD. Twenty-five patients were included in the analysis and a clinical improvement was recorded for 10/25 (40%) of them. Microbial alpha diversity showed a slight increase in clinical responders (P=0.271), while it decreased in patients who did not improved (P=0.05). A significant post-treatment increase in Faecalibacterium abundance was observed in patients with a positive response (log2FC 1.959, P=0.042). Roseburia abundance decreased in both groups, whereas Ruminococcus decreased only in patients who clinically improved. Clinical improvement consequent to rifaximin treatment is associated with an increase in Faecalibacterium abundance. Achieving a positive shift in the gut microbiota composition seems a key event to obtain a clinical benefit from treatment.

The gut microbiome has been implicated in cancer in several ways, as specific microbial signatures are known to promote cancer development and influence safety, tolerability and efficacy of therapies. The 'omics' technologies used for microbiome analysis continuously evolve and, although much of the research is still at an early stage, large-scale datasets of ever increasing size and complexity are being produced. However, there are varying levels of difficulty in realizing the full potential of these new tools, which limit our ability to critically analyse much of the available data. In this Perspective, we provide a brief overview on the role of gut microbiome in cancer and focus on the need, role and limitations of a machine learning-driven approach to analyse large amounts of complex health-care information in the era of big data. We also discuss the potential application of microbiome-based big data aimed at promoting precision medicine in cancer.

Fecal microbiota transplantation (FMT) is the infusion of feces from a healthy donor into the gut of a recipient to treat a dysbiosis-related disease. FMT has been proven to be a safe and effective treatment for Clostridioides difficile infection, but increasing evidence supports the role of FMT in other gastrointestinal and extraintestinal diseases. The aim of this review is to paint the landscape of current evidence of FMT in different fields of application (including irritable bowel syndrome, inflammatory bowel disease, liver disorders, decolonization of multidrug-resistant bacteria, metabolic disorders and neurological disorders), as well as to discuss the current regulatory scenario of FMT, and hypothesize future directions of FMT.

The digestive tract can be targeted by SARS-CoV-2 and its interactions with the immune system, and the lungs may have meaningful implications in the pathogenesis of COVID-19. This gastrointestinal involvement needs to be considered in clinical practice., Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a direct impact on the gastrointestinal system, as up to 50% of fecal samples from coronavirus disease 2019 (COVID-19) patients contain detectable viral RNA despite a negative rhino-pharyngeal swab. This finding, together with an intestinal expression of angiotensin conversion enzyme 2 protein, suggests a possible fecal-oral transmission for SARS-CoV-2. Furthermore, gastrointestinal (GI) symptoms are common in COVID-19 patients including watery diarrhea, vomiting—particularly in children—nausea, and abdominal pain. Pathogenesis of SARS-CoV-2 infection presents significant similarities to those of some immune-mediated diseases, such as inflammatory bowel diseases or rheumatoid arthritis, leading to the hypothesis that targeted therapies used for the treatment of immune-mediated disease could be effective to treat (and possibly prevent) the main complications of COVID-19. In this review, we synthesize the present and future impact of SARS-CoV-2 infection on the gastrointestinal system and on gastroenterology practice, hypothesizing a potential role of the “gut-lung axis” and perhaps of the gut and lung microbiota into the interindividual differential susceptibility to COVID-19 19 disease. Finally, we speculate on the reorganization of outpatient gastroenterology services, which need to consider, among other factors, the major psychological impact of strict lockdown measures on the whole population.

Aims Faecal microbiota transplantation (FMT) consists of the infusion of faeces from a healthy donor to the gastrointestinal tract of a recipient patient to treat disease associated with alterations in gut microbiota. The objective of this article was to describe laboratory workflow of an FMT laboratory to provide tips for preparing the faecal suspensions to be infused. Methods and results Twenty-stool solutions obtained from ten donors were prepared using two different protocols: magnet plate emulsion (MPE) and Seward StomacherTM Emulsion (SSE). We evaluated parameters such as preparation time, handiness, and aerobic and anaerobic microbial count. For three donors, we monitored bacterial counts after defrosting at different time-points. MPE requires more time than SSE. In terms of microbial load, both methods showed similar values, with small and statistically differences (P ≤ 0·05) regarding anaerobes in favour of SSE. Frozen aliquots showed the same bacterial load values after defrosting. Conclusion Although both methods allow an easy and available preparation of a stool suspension, SSE seems more suitable, particularly for stool banking. Aerobic and anaerobic species are preserved with both protocols; and safety for laboratory operators is guaranteed. Significance and impact of the study In recent years, FMT has become a fascinating and interesting subject. Nevertheless, there are no real guidelines describing laboratory facilities and procedures. This paper aims to be a useful and simple guide to increase the number FMT centres as much possible.

TPS407 Background: Renal cell carcinoma (RCC) is the 6° most common cancer in men and the 8° in women in the USA. In Italy RCC incidence was 11,500 new cases in 2017, while mortality was 3,371 cases in 2015. Increasing evidence suggests that response to immune checkpoint inhibitors (ICIs), a novel treatment for advanced RCC (aRCC) and other epithelial tumors, can be influenced by the patient gut microbiota. Fecal microbiota transplantation (FMT) is a novel treatment option aimed to restore healthy gut microbiota, and is the most effective therapy for recurrent C. difficile infection. Preliminary nonrandomized findings show that FMT is able to improve efficacy of ICIs in patients with advanced melanoma. The aim of this study is to evaluate, through a double-blinded placebo-controlled randomized clinical trial, the efficacy of targeted FMT (from donors who are responding to ICIs) in improving response rates to ICIs in subjects with aRCC. Methods: 50 patients who are about to receive, or have started by 12 months) responders to ICIs, and will be selected by following protocols recommended by international guidelines. Patients in the FMT group will always receive feces from the same donor throughout the three fecal transplants. Frozen fecal batches and frozen fecal capsules will be manufactured according to international guidelines. Patients will be followed-up 7, 15, 30, 90, 180, 270, and 360 days after randomization for clinical evaluation and collection of stool samples. Patients will also undergo radiological assessment at 90, 180, 270 and 360 days after randomization. Microbiome analysis will be performed with shotgun metagenomics. The primary endpoint is the progression-free survival (PFS) at 12 months. Secondary endpoints are: objective response rate at 12 months; overall survival at 12 months; adverse events after FMT; microbiome changes after FMT. Sample size calculation was based on the hypothesis that FMT can improve the 1-year PFS rate from 60% (reported 1-year PFS for SOC) to 80% wen associated to SOC. Clinical trial information: NCT04758507.

Liver disease and gut dysbiosis are strictly associated, and the pathophysiology of this bidirectional relationship has recently been the subject of several investigations. Growing evidence highlights the link between gut microbiota composition, impairment of the gut-liver axis, and the development or progression of liver disease. Therefore, the modulation of gut microbiota to maintain homeostasis of the gut-liver axis could represent a potential instrument to halt liver damage, modify the course of liver disease, and improve clinical outcomes. Among all the methods available to achieve this purpose, fecal microbiota transplantation (FMT) is one of the most promising, being able to directly reshape the recipient’s gut microbial communities. In this review, we report the main characteristics of gut dysbiosis and its pathogenetic consequences in cirrhotic patients, discussing the emerging data on the application of FMT for liver disease in different clinical settings.

Objective Type 1 diabetes (T1D) is characterised by islet autoimmunity and beta cell destruction. A gut microbiota–immunological interplay is involved in the pathophysiology of T1D. We studied microbiota-mediated effects on disease progression in patients with type 1 diabetes using faecal microbiota transplantation (FMT). Design Patients with recent-onset (

LINKED CONTENT This article is linked to Tian et al and Tian and Rong papers. To view these articles, visit https://doi.org/10.1111/apt.15731 and https://doi.org/10.1111/apt.15986

Background: Clostridioides difficile infection (CDI) is a risk factor for bloodstream infections (BSI). Fecal microbiota transplantation (FMT) is more effective than antibiotics in treating recurrent CDI, but its efficacy in preventing CDI-related BSI is uncertain. Objective: To assess incidence of primary BSI in patients with recurrent CDI treated with FMT compared with patients treated with antibiotics. Design: Prospective cohort study. FMT and antibiotic treated patients were matched using propensity score. Setting: Single academic medical center. Patients: 290 inpatients with recurrent CDI; 57 patients per treatment in matched cohort. Interventions: FMT or antibiotics. Measurements: Our primary outcome was the development of primary BSI within a 90-day follow-up. Secondary outcomes were length of hospitalization, and overall survival (OS) at 90 days. Results: 109 patients were treated with FMT, and 181 received antibiotics. Five patients in the FMT group and 40 in the antibiotic group developed BSI. Due to differences in the patients treated with FMT and antibiotics in a number of baseline characteristics including the number of recurrences and CDI severity, comparative analyses were limited to the matched cohort. Subjects in the FMT group experienced a 23% lower risk of developing BSI (95% confidence interval 10-35%), 14 fewer days of hospitalization (95% confidence interval 9-20 days), and a 32% increase in OS (95% confidence interval 16-47%) compared with the antibiotic group. Limitations: Non-randomized study with potential for unmeasured/residual confounding. Limited generalizability of the propensity score-matched cohort. Conclusion: In a propensity score-matched cohort, patients with recurrent CDI treated with FMT were less likely to develop primary BSI.

The gut microbiota and its genomic scaffold, exceeding the human one nearly 500 times, substantially affect human health and diseases. Host-microbe interactions, exerted through microbial biochemical and immunological activities, contain pathogen burden, control neurological and endocrine signalling, enterocyte wellness, energy biosynthesis, gut dysbiosis, complement gaps of host metabolic pathways, finally contributing to human physiology and disease within the gastrointestinal district and through gut-liver and gut-brain axis (1).

The burden of Clostridium difficile associated diarrhea is a worrying clinical issue worldwide, mainly as regarding the high incidence of recurrences after standard antibiotic therapy and the risk for more severe clinical manifestations. For this reason, new and more effective therapies are needed for the treatment of recurrent episodes. Fecal microbiota transplantation seems to be a valid tool considering the mechanism of action and the growing number of studies that demonstrate its clinical efficacy.

The human gastrointestinal tract is home to the most diverse microbial ecosystem in the human body and is made up of bacteria, viruses and eukarya. Collectively known as the gut microbiota, our knowledge of these microbial communities has historically been restricted by the relative limitations of culturing techniques. However, the recent development and utilisation of next-generation sequencing techniques has enhanced our understanding of its structure, diversity and function.There is emerging evidence that the gut microbiota plays a pivotal role in both health and disease. Perturbations to the structure and function of the gut microbiota are known to be associated with certain disease states. Therefore, manipulating the gut microbiota in an attempt to restore structure and function represents a promising therapeutic strategy. Recently, there has been a surge in clinical and scientific interest in manipulating the gut microbiota using a method called faecal microbiota transplantation. This increase in interest has gathered after it was shown in randomised controlled trials to be highly effective in treating recurrent Clostridium difficile infection.Despite success in treating recurrent Clostridium difficile, there remain many unknowns about how best to optimise its preparation, regulation, mode of delivery and safety. This review aims to summarise the literature surrounding the current knowledge regarding faecal microbiota transplantation and explore potential future research avenues that aim to enhance the safety, efficacy and utilisation of faecal microbiota transplantation. Keywords: Faecal microbiota transplantation, FMT, Microbiota, Microbiome, Bacteriotherapy

Background: Clostridium Difficile Infections (CDIs) have been increasing both in incidence and in severity, representing a big public health concern. Aim: The aim of this study was to evaluate the impact of a recently implemented Critical Pathway (CP) focused on patients with CDI in an Italian Teaching Hospital. Methods: The CP implementation consisted of intervention aimed to faster diagnosis and appropriateness in admission and discharge point of care; activation of a multidisciplinary team; staff training; information to patients and caregivers.In a pre-post retrospective observational study, volume, process and outcome indicators were analyzed. Findings: A total of 228 patients (128 in 2013 and 100 in 2016) were included. A decrease in the absolute number of access to the Emergency Department (p = 0.02) and an increase in hospitalization in more appropriate ward (ie gastroenterology ward, p

Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent Clostridioides difficile infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres.Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice,Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice.

INTRODUCTION Clostridium difficile or Clostridioides difficile (C. difficile) infection represents the most common cause of healthcare-associated infection. Over the last decades, the incidence and severity of C. difficile infection is rapidly increasing, with a significant impact on morbidity and mortality, and burden on health care system. Orally administered vancomycin and fidaxomicin are the therapeutic options of choice for initial C. difficile infection and fecal microbiota transplant for the recurrence infection. Furthermore, in recent years several new antibiotics with narrow-spectrum activity and low intestinal resorption have been developed, including surotomycin, cadazolid, and ridinilazol, and novel toxoid vaccines are expected to be efficacious in the prevention of C. difficile infection. Areas covered: Literature review was performed to select publications about current guidelines and phase-II/III trials on emerging drugs. These include novel antibiotics, monoclonal antibodies, vaccines, and fecal microbiota transplantation. Expert opinion: We have today a wide spectrum of promising therapeutic possibilities against infection. Pivotal future clinical trials may be crucial in developing effective strategies to optimize outcomes, mainly in high-risk population.

Lung cancer is one of the deadliest and most common malignancies in the world, representing one of the greatest challenges in cancer treatment. Immunotherapy is rapidly changing standard treatment schedule and outcomes for patients with advanced malignancies. However, several ongoing studies are still attempting to elucidate the biomarkers that could predict treatment response as well as the new strategies to improve antitumor immune system response ameliorating immunotherapy efficacy. The complex of bacteria, fungi, and other microorganisms, termed microbiota, that live on the epithelial barriers of the host, are involved in the initiation, progression, and dissemination of cancer. The functional role of microbiota has attracted an accumulating attention recently. Indeed, it has been demonstrated that commensal microorganisms are required for the maturation, education, and function of the immune system regulating the efficacy of immunotherapy in the anticancer response. In this review, we discuss some of the major findings depicting bacteria as crucial gatekeeper for the immune response against tumor and their role as driver of immunotherapy efficacy in lung cancer with a special focus on the distinctive role of gut and lung microbiota in the efficacy of immunotherapy treatment.

A new study shows that a sustainable faecal microbiota transplantation (FMT) treatment protocol, including anaerobic sample preparation, induces remission of active ulcerative colitis. The promising results are another piece in the puzzle, but it is not yet possible to draw conclusions and implement the procedure in clinical practice.

Colorectal cancer (CRC) is still a major threat for public health, as it is the third most common cancer in men and the second in women and it ranks second among tumors in terms of mortality. Evidence from the last decades emphasizes the complex role of gut microbial composition in CRC development. Historically, it is believed that dairy products, a source of lactobacilli and other lactic acid bacteria, are beneficial for human health and help in preventing CRC. We searched online literature for trials evaluating the preventive role of lactobacilli in CRC animal models. Most of selected studied assessed a relevant role of lactobacilli in preventing CRC and precursor lesions. Mechanisms through which this effect was achieved are supposed to regard immunomodulation, regulation of apoptosis, gut microbial modulation, genes expression, reduction of oxidative stress and others. Lactobacilli oral supplementation is reported to be effective in preventing CRC in animal models, even if the underlying mechanisms of action are still not fully understood.

Patients with non-celiac gluten sensitivity (NCGS) do not have celiac disease, but their symptoms improve after a gluten-free diet (GFD). However, to date, it is uncertain if gluten or other components of wheat are responsible for these symptoms. The aim of this study was to compare the effects of an organic durum wheat variety with those of standard commercial wheat in patients with known NCGS. We performed a double-blind randomized cross-over trial of 42 patients (mean age 45 years, 8 men) with NCGS diagnosed according to the Salerno criteria and adherence to GFD for at least 12 weeks from screening. Enrolled subjects were randomly assigned to one the following groups of treatment: (A) a two-week diet with Senatore Cappelli wheat variety pasta, (B) a two-week diet with standard commercial pasta. Then, after a two-week washout period on gluten-free diet, each patient crossed over to the other treatment group. Symptoms were assessed through a modified version of the Gastrointestinal Symptom Rating Scale (GSRS), tailored on NCGS. Between April 2018 and July 2018, 42 patients with NCGS were enrolled in the study (70.6% females), and 34 patients completed the study. Patients reported lower overall symptoms scores after eating Senatore Cappelli pasta than standard pasta (p = 0.03) and also significantly lower scores in several specific gastrointestinal and extra-intestinal symptoms after eating Senatore Cappelli pasta than standard pasta, specifically, bloating (p = 0.04), abdominal distention (p = 0.004), eructation (p = 0.01), flatus (p = 0.02), feeling of incomplete evacuation (p = 0.001), dermatitis (p = 0.01), and limb numbness (p = 0.03). In our study, patients with NCGS experienced lower gastrointestinal and extra-intestinal symptom scores after eating the Senatore Cappelli wheat variety than a standard commercial wheat. Should our preliminary results be confirmed by further studies, new dietary alternatives may be available to patients with NCGS, with consequent health, economic, and social benefits.