Low dose dietary contamination with deoxynivalenol mycotoxin exacerbates enteritis and colorectal cancer in mice.

Background: The mycotoxin deoxynivalenol (DON) is a frequent contaminant of grain and cereal products worldwide. Exposure to DON can cause gastrointestinal inflammation, disturb gut barrier function, and induce gut dysbiosis in vivo under basal conditions, but little is known about the effects of DON ingestion in individuals with pre-existing gastrointestinal disease.

Objectives: Mice were orally exposed to 10 and 100 μg/kg bw/day of DON, corresponding to 10 to 100-fold human tolerable daily intake concentrations, and to the translation in mice of current human daily intake.

The impact of the gut microbiome on extra-intestinal autoimmune diseases.

The prevalence of autoimmune diseases (ADs) worldwide has rapidly increased over the past few decades. Thus, in addition to the classical risk factors for ADs, such as genetic polymorphisms, infections and smoking, environmental triggers have been considered. Recent sequencing-based approaches have revealed that patients with extra-intestinal ADs, such as multiple sclerosis, rheumatoid arthritis, type 1 diabetes and systemic lupus erythematosus, have distinct gut microbiota compositions compared to healthy controls.

Dietary Modulation Alters Susceptibility to Listeria monocytogenes and Salmonella Typhimurium with or without a Gut Microbiota.

Food safety has considerably improved worldwide, yet infections with foodborne human enteric pathogens, such as spp. and Salmonella spp., still cause numerous hospitalizations and fatalities.

Leveraging diet to engineer the gut microbiome.

Autoimmune diseases, including inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, have distinct clinical presentations but share underlying patterns of gut microbiome perturbation and intestinal barrier dysfunction. Their potentially common microbial drivers advocate for treatment strategies aimed at restoring appropriate microbiome function, but individual variation in host factors makes a uniform approach unlikely. In this Perspective, we consolidate knowledge on diet-microbiome interactions in local inflammation, gut microbiota imbalance and host immune dysregulation.

Deprivation of dietary fiber in specific-pathogen-free mice promotes susceptibility to the intestinal mucosal pathogen .

The change of dietary habits in Western societies, including reduced consumption of fiber, is linked to alterations in gut microbial ecology. Nevertheless, mechanistic connections between diet-induced microbiota changes that affect colonization resistance and enteric pathogen susceptibility are still emerging. We sought to investigate how a diet devoid of soluble plant fibers impacts the structure and function of a conventional gut microbiota in specific-pathogen-free (SPF) mice and how such changes alter susceptibility to a rodent enteric pathogen.

Concentrated Raw Fibers Enhance the Fiber-Degrading Capacity of a Synthetic Human Gut Microbiome.

The consumption of prebiotic fibers to modulate the human gut microbiome is a promising strategy to positively impact health. Nevertheless, given the compositional complexity of the microbiome and its inter-individual variances, generalized recommendations on the source or amount of fiber supplements remain vague. This problem is further compounded by availability of tractable in vitro and in vivo models to validate certain fibers.

Constructing a gnotobiotic mouse model with a synthetic human gut microbiome to study host-microbe cross talk.

Reproducible models are necessary to address functional aspects of the gut microbiome in various diseases. Here, we present a gnotobiotic mouse model that allows for the investigation of specific microbial functions within the microbiome. We describe how to culture 14 different well-characterized human gut species and how to verify their proper colonization in germ-free mice.

Quantitative assay to detect bacterial glycan-degrading enzyme activities in mouse and human fecal samples.

The gut microbiome expresses a multitude of enzymes degrading polysaccharides in dietary plant fibers and in host-secreted mucus. The quantitative detection of these glycan-degrading enzymes in fecal samples is important to elucidate the functional activity of the microbiome in health and disease. We describe a protocol for detection of glycan-degrading enzyme activity in mouse and human fecal samples, namely sulfatase and four carbohydrate-active enzymes.

Gut Commensal-Induced IκBζ Expression in Dendritic Cells Influences the Th17 Response.

Intestinal commensal bacteria can have a large impact on the state of health and disease of the host. Regulation of Th17 cell development by gut commensals is known to contribute to their dichotomous role in promoting gut homeostasis and host defense, or development of autoimmune diseases. Yet, the underlying mechanisms remain to be fully elucidated.

The Heart Failure Readmission Intervention by Variable Early Follow-up (THRIVE) Study: A Pragmatic Randomized Trial.

Background: In-person clinic follow-up within 7 days after discharge from a heart failure hospitalization is associated with lower 30-day readmission. However, health systems and patients may find it difficult to complete an early postdischarge clinic visit, especially during the current pandemic. We evaluated the effect on 30-day readmission and death of follow-up within 7 days postdischarge guided by an initial structured nonphysician telephone visit compared with follow-up guided by an initial clinic visit with a physician.

Weak Agonistic LPS Restores Intestinal Immune Homeostasis.

Generated by gram-negative bacteria, lipopolysaccharides (LPSs) are one of the most abundant and potent immunomodulatory substances present in the intestinal lumen. Interaction of agonistic LPS with the host myeloid-differentiation-2/Toll-like receptor 4 (MD-2/TLR4) receptor complex results in nuclear factor κB (NF-κB) activation, followed by the robust induction of pro-inflammatory immune responses. Here we have isolated LPS from a common gut commensal, Bacteroides vulgatus mpk (BVMPK), which provides only weak agonistic activity.

Flagellin hypervariable region determines symbiotic properties of commensal Escherichia coli strains.

Escherichia coli represents a classical intestinal gram-negative commensal. Despite this commensalism, different E. coli strains can mediate disparate immunogenic properties in a given host.

: A Novel Invertebrate Model to Distinguish Intestinal Symbionts From Pathobionts.

Insects and mammals share evolutionary conserved innate immune responses to maintain intestinal homeostasis. We investigated whether the larvae of the greater wax moth may be used as an experimental organism to distinguish between symbiotic and pathobiotic , which are mammalian intestinal commensals. Oral application of the symbiont or pathobiont to resulted in clearly distinguishable innate immune responses that could be verified by analyzing similar innate immune components in mice and .

Fungi as Part of the Microbiota and Interactions with Intestinal Bacteria.

The human microbiota consists of bacteria, archaea, viruses, and fungi that build a highly complex network of interactions between each other and the host. While there are many examples for commensal bacterial influence on host health and immune modulation, little is known about the role of commensal fungi inside the gut community. Up until now, fungal research was concentrating on opportunistic diseases caused by fungal species, leaving the possible role of fungi as part of the microbiota largely unclear.

Proteome and phosphoproteome analysis of commensally induced dendritic cell maturation states.

Dendritic cells (DCs) can shape the immune system towards an inflammatory or tolerant state depending on the bacterial antigens and the environment they encounter. In this study we provide a proteomic catalogue of differentially expressed proteins between distinct DC maturation states, brought about by bacteria that differ in their endotoxicity. To achieve this, we have performed proteomics and phosphoproteomics on murine DC cultures.

Outer membrane vesicles blebbing contributes to B. vulgatus mpk-mediated immune response silencing.

The Gram negative intestinal symbiont Bacteroides vulgatus mpk is able to prevent from induction of colonic inflammation in Rag1 mice and promotes immune balance in Il2 mice. These inflammation-silencing effects are associated with B. vulgatus mpk-mediated induction of semi-mature dendritic cells, especially in the colonic lamina propria (cLP).

Symbiotic gut commensal bacteria act as host cathepsin S activity regulators.

Cathepsin S (CTSS) is a lysosomal protease whose activity regulation is important for MHC-II signaling and subsequent activation of CD4 T cell mediated immune responses. Dysregulation of its enzymatic activity or enhanced secretion into extracellular environments is associated with the induction or progression of several autoimmune diseases. Here we demonstrate that commensal intestinal bacteria influence secretion rates and intracellular activity of host CTSS and that symbiotic bacteria, i.

Extensive Mobilome-Driven Genome Diversification in Mouse Gut-Associated Bacteroides vulgatus mpk.

Like many other Bacteroides species, Bacteroides vulgatus strain mpk, a mouse fecal isolate which was shown to promote intestinal homeostasis, utilizes a variety of mobile elements for genome evolution. Based on sequences collected by Pacific Biosciences SMRT sequencing technology, we discuss the challenges of assembling and studying a bacterial genome of high plasticity. Additionally, we conducted comparative genomics comparing this commensal strain with the B.

Structure and function: Lipid A modifications in commensals and pathogens.

Lipopolysaccharides (LPS) of Gram negative bacteria are one of the most potent stimulators of the host innate immune system and LPS recognition is essential for the host organism to clear infections of invading bacterial pathogens. Here we review on the latest research on how LPS is sensed by host cells and how distinct LPS structures differentially modulate the strength of the host immune response. Much is known about host immunological reactions towards pathogens via recognition of their LPS, as well as strategies of pathogens to modulate their LPS structure in order to evade the immune system.

Molecular Mechanisms of Induction of Tolerant and Tolerogenic Intestinal Dendritic Cells in Mice.

How does the host manage to tolerate its own intestinal microbiota? A simple question leading to complicated answers. In order to maintain balanced immune responses in the intestine, the host immune system must tolerate commensal bacteria in the gut while it has to simultaneously keep the ability to fight pathogens and to clear infections. If this tender equilibrium is disturbed, severe chronic inflammatory reactions can result.

Post-discharge Follow-up Characteristics Associated With 30-Day Readmission After Heart Failure Hospitalization.

Background: Readmission within 30 days after hospitalization for heart failure (HF) is a major public health problem.

Objective: To examine whether timing and type of post-discharge follow-up impacts risk of 30-day readmission in adults hospitalized for HF.

Design: Nested matched case-control study (January 1, 2006-June 30, 2013).

A novel approach for reliable detection of cathepsin S activities in mouse antigen presenting cells.

Cathepsin S (CTSS) is a eukaryotic protease mostly expressed in professional antigen presenting cells (APCs). Since CTSS activity regulation plays a role in the pathogenesis of various autoimmune diseases like multiple sclerosis, atherosclerosis, Sjögren's syndrome and psoriasis as well as in cancer progression, there is an ongoing interest in the reliable detection of cathepsin S activity. Various applications have been invented for specific detection of this enzyme.