The Future of Microbiome Therapeutics.

The human microbiome exerts profound influence over various biological processes within the body. Unlike many host determinants, it represents a readily accessible target for manipulation to promote health benefits. However, existing commercial microbiome-directed products often exhibit low efficacy.

Bile acid-induced metabolic changes in the colon promote Enterobacteriaceae expansion and associate with dysbiosis in Crohn's disease.

Bile acids (BAs) affect the growth of potentially pathogenic commensals, including those from the Enterobacteriaceae family, which are frequently overrepresented in inflammatory bowel disease (IBD). BAs are normally reabsorbed in the ileum for recycling and are often increased in the colonic lumina of patients with IBD, including those with Crohn's disease (CD). Here, we investigated the influence of BAs on gut colonization by Enterobacteriaceae.

Fecal microbiota transplantation: current challenges and future landscapes.

SUMMARYGiven the importance of gut microbial homeostasis in maintaining health, there has been considerable interest in developing innovative therapeutic strategies for restoring gut microbiota. One such approach, fecal microbiota transplantation (FMT), is the main "whole gut microbiome replacement" strategy and has been integrated into clinical practice guidelines for treating recurrent infection (rCDI). Furthermore, the potential application of FMT in other indications such as inflammatory bowel disease (IBD), metabolic syndrome, and solid tumor malignancies is an area of intense interest and active research.

Microbiome changes under enteral deprivation are dynamic and dependent on intestinal location.

Background: The microbiome has a pivotal role in intestinal health, and nutrition has a major role shaping its structure. Enteral deprivation, in which no oral/enteral nutrition is administered, is common in hospitalized/gastrointestinal patients. The dynamics that enteral deprivation exerts on the microbial community, specifically in the small intestine, are not well understood.

Comparative evaluation of a language model and human specialists in the application of European guidelines for the management of inflammatory bowel diseases and malignancies.

Background: Society guidelines on colorectal dysplasia screening, surveillance, and endoscopic management in inflammatory bowel disease (IBD) are complex, and physician adherence to them is suboptimal. We aimed to evaluate the use of ChatGPT, a large language model, in generating accurate guideline-based recommendations for colorectal dysplasia screening, surveillance, and endoscopic management in IBD in line with European Crohn's and Colitis Organization (ECCO) guidelines.

Methods: 30 clinical scenarios in the form of free text were prepared and presented to three separate sessions of ChatGPT and to eight gastroenterologists (four IBD specialists and four non-IBD gastroenterologists).

A personalized network framework reveals predictive axis of anti-TNF response across diseases.

Personalized treatment of complex diseases has been mostly predicated on biomarker identification of one drug-disease combination at a time. Here, we use a computational approach termed Disruption Networks to generate a data type, contextualized by cell-centered individual-level networks, that captures biology otherwise overlooked when performing standard statistics. This data type extends beyond the "feature level space", to the "relations space", by quantifying individual-level breaking or rewiring of cross-feature relations.

The Effect of Nutrient Deprivation on Early Life Small Intestinal Mucosal Microbiome and Host Proteome.

Background: Nutrition plays a vital role in shaping the intestinal microbiome. However, many hospitalized children undergo periods of fasting during medical treatment. Changes to the small intestinal microbiota in early life in the setting of enteral deprivation have not been well described.

Microbiota-mediated effects of Parkinson's disease medications on Parkinsonian non-motor symptoms in male transgenic mice.

Parkinson's disease (PD) is characterized by motor symptoms and a loss of dopaminergic neurons, as well as a variety of non-motor symptoms, including constipation, depression, and anxiety. Recently, evidence has also accumulated for a link between gut microbiota and PD. Most PD patients are on dopamine replacement therapy, primarily a combination of L-DOPA and carbidopa; however, the effect of these medications on the microbiota and non-motor symptoms in PD is still unclear.

Multiple micronutrient deficiencies in early life cause multi-kingdom alterations in the gut microbiome and intrinsic antibiotic resistance genes in mice.

Globally, ~340 million children suffer from multiple micronutrient deficiencies, accompanied by high pathogenic burden and death due to multidrug-resistant bacteria. The microbiome is a reservoir of antimicrobial resistance (AMR), but the implications of undernutrition on the resistome is unclear. Here we used a postnatal mouse model that is deficient in multiple micronutrients (that is, zinc, folate, iron, vitamin A and vitamin B12 deficient) and shotgun metagenomic sequencing of faecal samples to characterize gut microbiome structure and functional potential, and the resistome.

Multiple micronutrient deficiencies alter energy metabolism in host and gut microbiome in an early-life murine model.

Introduction: Micronutrients perform a wide range of physiological functions essential for growth and development. However, most people still need to meet the estimated average requirement worldwide. Globally, 2 billion people suffer from micronutrient deficiency, most of which are co-occurring deficiencies in children under age five.

Effects of Gut Microbiota Alterations on Motor, Gastrointestinal, and Behavioral Phenotype in a Mouse Model of Parkinson's Disease.

Background: Parkinson's disease (PD) is a multi-system disorder consisting of not only classic motor symptoms but also a variety of non-motor symptoms including gastrointestinal (GI) dysfunction and mood disorders. The gut microbiota has been suggested to play a role in modulating PD motor and non-motor features, although the causality and mechanisms behind these proposed interactions remains largely understudied.

Objective: In this study, we aimed to provide in-depth characterization of an established mouse model of PD (transgenic (TG) SNCA A53T) and experimentally address how changes to the gut microbiota impact the PD-like phenotype.

Omitting Ciprofloxacin Prophylaxis in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation and Its Impact on Clinical Outcomes and Microbiome Structure.

Fluoroquinolone prophylaxis during allogeneic hematopoietic stem cell transplantation (allo-HSCT) reduces bloodstream infections. However, this practice affects the gut microbiome and potentially increases dysbiosis, which is closely related to transplantation outcomes, and lower gastrointestinal (GI) tract acute graft-versus-host disease (GVHD). This study assessed the impact of omitting ciprofloxacin prophylaxis on GI GVHD, clinical outcomes, and microbiome composition in patients undergoing allo-HSCT.

The effect of indirect calorimetry guided isocaloric nutrition on mortality in critically ill patients-a systematic review and meta-analysis.

Indirect calorimetry (IC)-guided nutrition might positively affect the clinical outcome of critically ill patients. In this systematic review and meta-analysis, our objective was to assess the benefit of isocaloric nutrition guided by IC, compared to hypocaloric nutrition, for critically ill patients admitted to the intensive care unit (ICU). We performed a systematic review of all randomized controlled trials published through January 2021, assessing the benefit of isocaloric nutrition guided by IC.

Risk Factors for Bacteremia After Endoscopic Procedures in Hospitalized Patients With a Focus on Neutropenia.

Background: The risk for bacteremia following endoscopic procedures varies among studies. A low neutrophil count is considered as a risk factor.

Objective: To assess risk factors for bacteremia following endoscopic procedures, focusing on neutropenia.

Efficacy of a hospital policy of selective digestive decontamination for carbapenem-resistant Enterobacterales carriers: prospective before-after study.

A single-centre interrupted time series quasi-experimental study was undertaken to assess whether a hospital policy of selective digestive decontamination (SDD, gentamicin/amikacin with neomycin) administered to carbapenem-resistant Enterobacterales (CRE) carriers would reduce the duration of carriage and contain the spread of CRE. No significant difference in time to CRE eradication was observed between the observation (12 months, 120 patients) and intervention (12 months, 101 patients) periods. No change in the trend of new in-hospital CRE acquisitions or bacteraemia during the intervention was detected.

Oral Capsulized Fecal Microbiota Transplantation for Eradication of Carbapenemase-producing Enterobacteriaceae Colonization With a Metagenomic Perspective.

Background: Carbapenemase-producing Enterobacteriaceae (CPE) infections lead to considerable morbidity and mortality. We assessed the potential of fecal microbiota transplantation (FMT) to eradicate CPE carriage and aimed to explain failure or success through microbiome analyses.

Methods: In this prospective cohort study, all consenting eligible CPE carriers received oral capsulized FMT for 2 days.

New-Onset of Crohn's Disease Is Associated with Antistreptolysin O Positive Titers.

Objective: Different infectious agents have been presumed to be candidates acting as an etiologic factor or trigger of Crohn's disease (CD). Group A (GAS) is a common human infection agent that can also trigger post-infectious immune-mediated conditions. The current study aimed to examine whether the immunogenic activity induced by GAS may trigger new-onset of CD.

Does early corticosteroid therapy affect prognosis in IBD patients hospitalized with Clostridioides difficile infection?

Background: Corticosteroids (CS) therapy to Clostridioides difficile infection (CDI) in inflammatory bowel disease (IBD) flares may worsen CDI outcomes.

Aim: Assess the impact of early CS exposure on outcomes of IBD patients diagnosed with CDI.

Methods: Retrospective study of IBD patients admitted with first-time CDI between 2002 and 2018.

Infliximab-Tumor Necrosis Factor Complexes Elicit Formation of Anti-Drug Antibodies.

Background & Aims: Some patients develop anti-drug antibodies (ADAs), which reduce the efficacy of infliximab, a monoclonal antibody against tumor necrosis factor (TNF), in the treatment of immune-mediated diseases, including inflammatory bowel diseases. ADAs arise inconsistently, and it is not clear what factors determine their formation. We investigated features of the immune system, the infliximab antibody, and its complex with TNF that might contribute to ADA generation.

Risk factors for mortality among carbapenem-resistant enterobacteriaceae carriers with focus on immunosuppression.

Objectives: To identify risk factors for mortality in a cohort of carbapenem-resistant enterobacteriaceae (CRE) carriers, focusing on immunosuppression and other risk factors known at the time of CRE carriage detection.

Methods: We prospectively followed all new and known CRE carriers admitted between June 2016 and June 2017 to a single tertiary center in Israel. Patients were included in the study after confirmation of the carrier state.

Regulation of S100A8 Stability by RNF5 in Intestinal Epithelial Cells Determines Intestinal Inflammation and Severity of Colitis.

Inflammatory bowel disease (IBD) is prevalent, but the mechanisms underlying disease development remain elusive. We identify a role for the E3 ubiquitin ligase RNF5 in IBD. Intestinal epithelial cells (IECs) express a high level of RNF5, while the colon of Rnf5 mice exhibits activated dendritic cells and intrinsic inflammation.