Publications by authors named "Hornef M"

Postnatal establishment of enteric metabolic, host-microbial and immune homeostasis is the result of precisely timed and tightly regulated developmental and adaptive processes. Here, we show that infection with the invasive enteropathogen Typhimurium results in accelerated maturation of the neonatal epithelium with premature appearance of antimicrobial, metabolic, developmental, and regenerative features of the adult tissue. Using conditional Myd88-deficient mice, we identify the critical contribution of immune cell-derived mediators.

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  • - Sepsis involves an out-of-control immune response, making it challenging to treat effectively; recent research shows that nanomedicines can help in this regard.
  • - In a mouse model, dexamethasone liposomes modified with cRGD peptides effectively target and engage neutrophils, allowing them to accumulate at sites of infection and reduce harmful immune responses.
  • - The targeted liposomes also lower levels of immature neutrophils and inflammatory cytokines, while maintaining beneficial IL-10 levels, showcasing a dual approach of both targeting neutrophils for therapy and using them to deliver drugs.
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acts both as a colonizing commensal bacterium and invasive pathogen. Nasal colonization is associated with an increased risk of infection caused by the identical strain. In patients with atopic dermatitis (AD), the degree of colonization is associated with the severity of the disease.

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  • Gut-draining mesenteric and celiac lymph nodes are essential for promoting tolerance to food and microbes by helping to generate regulatory T cells in the immune system.
  • A brief gastrointestinal infection during infancy disrupts the ability of celiac lymph nodes to induce these protective Tregs by changing the characteristics of specific supporting cells within the lymph nodes.
  • Lower levels of vitamin A after infection lead to lasting functional impairments in celiac lymph nodes, but early vitamin A treatment could mitigate these negative effects.
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The intestinal epithelium is the first line of defense against enteric pathogens. Removal of infected cells by exfoliation prevents mucosal translocation and systemic infection in the adult host, but is less commonly observed in the neonatal intestine. Instead, here, we describe non-professional efferocytosis of Salmonella-infected enterocytes by neighboring epithelial cells in the neonatal intestine.

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Bile acid (BA) metabolism is a complex system that includes a wide variety of primary and secondary, as well as conjugated and unconjugated BAs that undergo continuous enterohepatic circulation (EHC). Alterations in both composition and dynamics of BAs have been associated with various diseases. However, a mechanistic understanding of the relationship between altered BA metabolism and related diseases is lacking.

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Background: Synthetic mesh material is of great importance for surgical incisional hernia repair. The physical and biochemical characteristics of the mesh influence mechanical stability and the foreign body tissue reaction. The influence on bacterial infections, however, remains ill-defined.

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  • Early-life immune development is essential for long-term health, but the factors influencing postnatal immune maturation are not well understood.
  • The study focused on mononuclear phagocytes in Peyer's patches, showing significant age-related changes that led to reduced T cell priming in young organisms.
  • The research identified that the differentiation of follicle-associated epithelium M cells is crucial for driving the maturation of these immune cells after weaning.
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The gut and the liver are characterized by mutual interactions between both organs, the microbiome, diet and other environmental factors. The sum of these interactions is conceptualized as the gut-liver axis. In this Review we discuss the gut-liver axis, concentrating on the barriers formed by the enterohepatic tissues to restrict gut-derived microorganisms, microbial stimuli and dietary constituents.

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The mucosal immune system of neonates goes through successive, non-redundant phases that support the developmental needs of the infant and ultimately establish immune homeostasis. These phases are informed by environmental cues, including dietary and microbial stimuli, but also evolutionary developmental programming that functions independently of external stimuli. The immune response to exogenous stimuli is tightly regulated during early life; thresholds are set within this neonatal "window of opportunity" that govern how the immune system will respond to diet, the microbiota, and pathogenic microorganisms in the future.

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  • Scientists are debating whether a fetus and its surroundings are home to stable groups of tiny living things called microbes during a healthy pregnancy.
  • Recent studies suggest that when they find these microbes, it could be because of mistakes during the testing process, not that the fetus actually has them.
  • Understanding these findings is important for learning how our immune system develops and shows that studying tiny living things in places with very few of them can be really tricky, so we need to use different science methods to get it right.
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Background & Aims: Growing evidence supports a role of gut-derived metabolites in nonalcoholic fatty liver disease (NAFLD), but the relation of endotoxin levels with gut permeability and NAFLD stage remains unclear. This systematic review with meta-analysis aims to provide further insights.

Methods: PubMed, Embase, and Cochrane Library were searched for studies published until January 2022 assessing blood endotoxins in patients with NAFLD.

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The virulence factors of the opportunistic human pathogen have been a main subject of research. In contrast, limited information is available on the mechanisms that allow the bacterium to accommodate to the conditions during carriage, a prerequisite for pathogenicity. Here, we tested the hypothesis that the adaptation of at different anatomical sites is reflected by differential gene regulation.

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Hypoxia-inducible transcription factor 1 (HIF-1) has been shown to enhance microbial killing and ameliorate the course of bacterial infections. While the impact of HIF-1 on inflammatory diseases of the gut has been studied intensively, its function in bacterial infections of the gastrointestinal tract remains largely elusive. With the help of a publicly available gene expression data set, we inferred significant activation of HIF-1 after oral infection of mice with Salmonella enterica serovar Typhimurium.

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Objective: The early window of opportunity describes the timeframe after birth in which essential interactions of the immune system and the newly developing microbiota take place. The infant's immune system has to be reactive to invading pathogens and at the same time tolerant to dietary antigens. If the mechanisms of defense and tolerance induction are disturbed, the risk of infections or allergies is increased.

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Objective: Among non-communicable diseases, the prevalence of allergic diseases has increased significantly in the new millennium. The increase of allergic diseases is linked to the changing environment of infants.

Methods: This narrative review summarizes the discussions and conclusions from the 8 Human Milk Workshop.

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The healthy human epidermis provides physical protection and is impenetrable for pathogenic microbes. Nevertheless, commensal and pathogen bacteria such as are able to colonize the skin surface, which may subsequently lead to infection. To identify and characterize regulatory elements facilitating adaptation of to the human skin environment we used tissue explants and quantified gene transcription during co-culture.

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pathogenicity island (SPI) 2 type three secretion system (T3SS)-mediated effector molecules facilitate bacterial survival in phagocytes but their role in the intestinal epithelium remains ill-defined. Using our neonatal murine infection model in combination with SPI2 reporter technology and RNA-Seq of sorted primary enterocytes, we demonstrate expression of SPI2 effector molecules by intraepithelial Typhimurium . Typhimurium).

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D-Allulose, also referred to as psicose, is a C3-epimer of D-fructose used as a sugar substitute in low energy products. It can be formed naturally during processing of food and drinks containing sucrose and fructose or is prepared by chemical synthesis or via enzymatic treatment with epimerases from fructose. Estimated intakes via Western style diets including sweetened beverages are below 500 mg per d but, when used as a sugar replacement, intake may reach 10 to 30 g per d depending on the food consumed.

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Education of our intestinal immune system early in life strongly influences adult health. This education strongly relies on series of events that must occur in well-defined time windows. From initial colonization by maternal-derived microbiota during delivery to dietary changes from mother's milk to solid foods at weaning, these early-life events have indeed long-standing consequences on our immunity, facilitating tolerance to environmental exposures or, on the contrary, increasing the risk of developing noncommunicable diseases such as allergies, asthma, obesity, and inflammatory bowel diseases.

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At the transition from intrauterine to postnatal life, drastic alterations are mirrored by changes in cellular immunity. These changes are in part immune cell intrinsic, originate in the replacement of fetal cells, or result from global regulatory mechanisms and adaptation to changes in the tissue microenvironment. Overall, longer developmental trajectories are intersected by events related to mother-infant separation, birth cues, acquisition of microbiota and metabolic factors.

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The enteric microbiota exerts a major influence on the host. It promotes food degradation, nutrient absorption, immune maturation and protects from infection with pathogenic microorganisms. However, certain compositional alterations also enhance the risk to develop metabolic, inflammatory and immune-mediated diseases.

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Abdominal infections including cholangitis represent a major problem in patients with perihilar cholangiocarcinoma (pCCA). Thus, we investigated bacterial colonization of the bile ducts and determined its impact on postoperative outcome focusing on abdominal infections. A cohort of 95 pCCA patients who underwent surgery between 2010 and 2019 with available intraoperative microbial bile cultures were analyzed regarding bile duct colonization and postoperative abdominal infection by group comparisons and logistic regressions.

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