Investigating the impact of antibiotic-induced dysbiosis on protection from colitis by mouse colonic innate lymphoid cells.

Innate lymphoid cells (ILCs) play a critical role in maintaining intestinal health in homeostatic and diseased conditions. During infection (CDI), IL-33 activates ILC2 to protect from colonic damage and mortality. The function of IL-33 and ILC is tightly regulated by the intestinal microbiota.

Systems-ecology designed bacterial consortium protects from severe infection.

Fecal Microbiota Transplant (FMT) is an emerging therapy that has had remarkable success in treatment and prevention of recurrent infection (rCDI). FMT has recently been associated with adverse outcomes such as inadvertent transfer of antimicrobial resistance, necessitating development of more targeted bacteriotherapies. To address this challenge, we developed a novel systems biology pipeline to identify candidate probiotic strains that would be predicted to interrupt pathogenesis.

Binary Toxin Binding Component Increases Virulence in a Hamster Model.

Background: is the leading cause of hospital-acquired gastrointestinal infection, in part due to the existence of binary toxin (CDT)-expressing hypervirulent strains. Although the effects of the CDT holotoxin on disease pathogenesis have been previously studied, we sought to investigate the role of the individual components of CDT during in vivo infection.

Methods: To determine the contribution of the separate components of CDT during infection, we developed strains of expressing either CDTa or CDTb individually.

The Gut Bacterial Community Potentiates Clostridioides difficile Infection Severity.

The severity of Clostridioides difficile infections (CDI) has increased over the last few decades. Patient age, white blood cell count, and creatinine levels as well as C. difficile ribotype and toxin genes have been associated with disease severity.

Binary Toxin Expression by Is Associated With Worse Disease.

Background: The incidence of infection (CDI) has increased over the past 2 decades and is considered an urgent threat by the Centers for Disease Control and Prevention. Hypervirulent strains such as ribotype 027, which possess genes for the additional toxin binary toxin (CDT), are contributing to increased morbidity and mortality.

Methods: We retrospectively tested stool from 215 CDI patients for CDT by enzyme-linked immunosorbent assay (ELISA).

Novel Drivers of Virulence in Clostridioides difficile Identified via Context-Specific Metabolic Network Analysis.

The pathogen Clostridioides difficile causes toxin-mediated diarrhea and is the leading cause of hospital-acquired infection in the United States. Due to growing antibiotic resistance and recurrent infection, targeting C. difficile metabolism presents a new approach to combat this infection.

The IL-33-ILC2 pathway protects from amebic colitis.

Entamoeba histolytica is a pathogenic protozoan parasite that causes intestinal colitis, diarrhea, and in some cases, liver abscess. Through transcriptomics analysis, we observed that E. histolytica infection was associated with increased expression of IL-33 mRNA in both the human and murine colon.

Optimizing a Multi-Component Intranasal Vaccine Formulation Using a Design of Experiments Strategy.

Amebiasis is a neglected tropical disease caused by a. Although the disease burden varies geographically, amebiasis is estimated to account for some 55,000 deaths and millions of infections globally per year. Children and travelers are among the groups with the greatest risk of infection.

Protection from Lethal Clostridioides difficile Infection via Intraspecies Competition for Cogerminant.

, a Gram-positive, spore-forming bacterium, is the primary cause of infectious nosocomial diarrhea. Antibiotics are a major risk factor for infection (CDI), as they disrupt the gut microbial community, enabling increased germination of spores and growth of vegetative To date, the only single-species bacterial preparation that has demonstrated efficacy in reducing recurrent CDI in humans is nontoxigenic Using multiple infection models, we determined that precolonization with a less virulent strain is sufficient to protect from challenge with a lethal strain of , surprisingly even in the absence of adaptive immunity. Additionally, we showed that protection is dependent on high levels of colonization by the less virulent strain and that it is mediated by exclusion of the invading strain.

Host Protective Mechanisms to Intestinal Amebiasis.

The protozoan parasite Entamoeba histolytica is the causative agent of amebiasis, an infection that manifests as colitis and, in some cases, liver abscess. A better understanding of host protective factors is key to developing an effective remedy. Recently, significant advances have been made in understanding the mechanisms of MUC2 production by goblet cells upon amebic infection, regulation of antimicrobial peptide production by Paneth cells, the interaction of commensal microbiota with immune stimulation, and host genetics in conferring protection from amebiasis.

Anti-toxin antibody is not associated with recurrent Clostridium difficile infection.

Clostridium difficile infection (CDI) recurs in ∼20% of patients. Prior studies indicated that antibody responses directed against the C. difficile toxins A and B were potentially associated with lower risk of recurrent CDI.

Lewis Blood-group Antigens Are Associated With Altered Susceptibility to Shigellosis.

In a cohort of infants, we found that lack of the Lewis histo-blood group antigen was associated with increased susceptibility to shigellosis. Broadly inhibiting fucosylation in epithelial cells in vitro decreased invasion by Shigella flexneri. These results support a role for fucosylated glycans in susceptibility to shigellosis.

Gut microbiome communication with bone marrow regulates susceptibility to amebiasis.

The microbiome provides resistance to infection. However, the underlying mechanisms are poorly understood. We demonstrate that colonization with the intestinal bacterium Clostridium scindens protects from Entamoeba histolytica colitis via innate immunity.

Interleukin-22-mediated host glycosylation prevents Clostridioides difficile infection by modulating the metabolic activity of the gut microbiota.

The involvement of host immunity in the gut microbiota-mediated colonization resistance to Clostridioides difficile infection (CDI) is incompletely understood. Here, we show that interleukin (IL)-22, induced by colonization of the gut microbiota, is crucial for the prevention of CDI in human microbiota-associated (HMA) mice. IL-22 signaling in HMA mice regulated host glycosylation, which enabled the growth of succinate-consuming bacteria Phascolarctobacterium spp.

IL-33 drives group 2 innate lymphoid cell-mediated protection during Clostridium difficile infection.

Clostridium difficile (C. difficile) incidence has tripled over the past 15 years and is attributed to the emergence of hypervirulent strains. While it is clear that C.

Colitis-Induced Th17 Cells Increase the Risk for Severe Subsequent Clostridium difficile Infection.

Clostridium difficile infection (CDI) is the number one hospital-acquired infection in the United States. CDI is more common and severe in inflammatory bowel disease patients. Here, we studied the mechanism by which prior colitis exacerbates CDI.

The Gut Microbiota Is Associated with Clearance of Clostridium difficile Infection Independent of Adaptive Immunity.

() , a Gram-positive, anaerobic bacterium, is the leading single cause of nosocomial infections in the United States. A major risk factor for infection (CDI) is prior exposure to antibiotics, as they increase susceptibility to CDI by altering the membership of the microbial community enabling colonization. The importance of the gut microbiota in providing protection from CDI is underscored by the reported 80 to 90% success rate of fecal microbial transplants in treating recurrent infections.

Alters the Structure and Metabolism of Distinct Cecal Microbiomes during Initial Infection To Promote Sustained Colonization.

Susceptibility to infection (CDI) is primarily associated with previous exposure to antibiotics, which compromise the structure and function of the gut bacterial community. Specific antibiotic classes correlate more strongly with recurrent or persistent infection. As such, we utilized a mouse model of infection to explore the effect of distinct antibiotic classes on the impact that infection has on community-level transcription and metabolic signatures shortly following pathogen colonization and how those changes may associate with persistence of Untargeted metabolomic analysis revealed that infection had significantly larger impacts on the metabolic environment across cefoperazone- and streptomycin-pretreated mice, which became persistently colonized compared to clindamycin-pretreated mice, where infection quickly became undetectable.

Colonizes Alternative Nutrient Niches during Infection across Distinct Murine Gut Microbiomes.

is the largest single cause of hospital-acquired infection in the United States. A major risk factor for infection (CDI) is prior exposure to antibiotics, as they disrupt the gut bacterial community which protects from colonization. Multiple antibiotic classes have been associated with CDI susceptibility, many leading to distinct community structures stemming from variation in bacterial targets of action.

A whole new ball game: Stem cell-derived epithelia in the study of host-microbe interactions.

Recent advances in developmental and stem cell biology have resulted in techniques that enable the generation and maintenance of complex epithelium in vitro. While these models have been utilized to study host development and disease, a renewed appreciation of host-microbe interactions has sparked interest in employing these new techniques to study microbes at the epithelial interface. Here we review the current advances in host-microbe interactions that have resulted from experiments using these complex epithelia.

Overdiagnosis of Clostridium difficile Infection in the Molecular Test Era.

Importance: Clostridium difficile is a major cause of health care-associated infection, but disagreement between diagnostic tests is an ongoing barrier to clinical decision making and public health reporting. Molecular tests are increasingly used to diagnose C difficile infection (CDI), but many molecular test-positive patients lack toxins that historically defined disease, making it unclear if they need treatment.

Objective: To determine the natural history and need for treatment of patients who are toxin immunoassay negative and polymerase chain reaction (PCR) positive (Tox-/PCR+) for CDI.

The rest of the story: the microbiome and gastrointestinal infections.

Bacterial infectious diseases are studied primarily as a host-pathogen dyad. However it is increasingly apparent that the gut microbial community is an important participant in these interactions. The gut microbiota influences bacterial infections in a number of ways, including via bacterial metabolism, stimulation of host immunity and direct bacterial antagonism.

Persistence and toxin production by Clostridium difficile within human intestinal organoids result in disruption of epithelial paracellular barrier function.

Clostridium difficile is the leading cause of infectious nosocomial diarrhea. The pathogenesis of C. difficile infection (CDI) results from the interactions between the pathogen, intestinal epithelium, host immune system, and gastrointestinal microbiota.