Gut microbiota dysbiosis induced by acute pancreatitis (AP) exacerbates pancreatic injury and systemic inflammatory responses. The alleviation of gut microbiota dysbiosis through faecal microbiota transplantation (FMT) is considered a potential strategy to reduce tissue damage and inflammation in many clinical disorders. Here, we aim to investigate the effect of gut microbiota and microbiota‐derived metabolites on AP and further clarify the mechanisms associated with pancreatic damage and inflammation.

Gut microbiota‐derived nicotinamide mononucleotide alleviates acute pancreatitis by activating pancreatic SIRT3 signalling

The gastrointestinal tract contains trillions of microorganisms, which are central to human health. Lactobacilli are considered beneficial microbiota members and are often used in probiotics, but their molecular functions, and especially those which are metal-dependent, remain poorly defined. ABSTRACT Lactobacillus is a genus of Gram-positive bacteria and comprises a major part of the lactic acid bacteria group that converts sugars to lactic acid. Lactobacillus species found in the gut microbiota are considered beneficial to human health and commonly used in probiotic formulations, but their molecular functions remain poorly defined. Microbes require metal ions for growth and function and must acquire them from the surrounding environment. Therefore, lactobacilli need to compete with other gut microbes for these nutrients, although their metal requirements are not well-understood. Indeed, the abundance of lactobacilli in the microbiota is frequently affected by dietary intake of essential metals like zinc, manganese, and iron, but few studies have investigated the role of metals, especially zinc, in the physiology and metabolism of Lactobacillus species. Here, we investigated metal uptake by quantifying total cellular metal contents and compared how transition metals affect the growth of two distinct Lactobacillus species, Lactobacillus plantarum ATCC 14917 and Lactobacillus acidophilus ATCC 4356. When grown in rich or metal-limited medium, both species took up more manganese, zinc, and iron compared with other transition metals measured. Distinct zinc-, manganese- and iron-dependent patterns were observed in the growth kinetics for these species and while certain levels of each metal promoted the growth kinetics of both Lactobacillus species, the effects depend significantly on the culture medium and growth conditions. IMPORTANCE The gastrointestinal tract contains trillions of microorganisms, which are central to human health. Lactobacilli are considered beneficial microbiota members and are often used in probiotics, but their molecular functions, and especially those which are metal-dependent, remain poorly defined. Abundance of lactobacilli in the microbiota is frequently affected by dietary intake of essential metals like manganese, zinc, and iron, but results are complex, sometimes contradictory, and poorly predictable. There is a significant need to understand how host diet and metabolism will affect the microbiota, given that changes in microbiota composition are linked with disease and infection. The significance of our research is in gaining insight to how metals distinctly affect individual Lactobacillus species, which could lead to novel therapeutics and improved medical treatment. Growth kinetics and quantification of metal contents highlights how distinct species can respond differently to varied metal availability and provide a foundation for future molecular and mechanistic studies.

https://doi.org/10.1128/spectrum.01006-21

Differential Effects of Transition Metals on Growth and Metal Uptake for Two Distinct Lactobacillus Species

The slightest change in the extra/intracellular concentration of metal ions results in amplified effects by signaling cascades that regulate both cell fate within the tumor microenvironment and immune status, which influences the network of antitumor immunity through various pathways. Based on the fact that metal ions influence the fate of cancer cells and participate in both innate and adaptive immunity, they are widely applied in antitumor therapy as immune modulators. Moreover, nanomedicine possesses the advantage of precise delivery and responsive release, which can perfectly remedy the drawbacks of metal ions, such as low target selectivity and systematic toxicity, thus providing an ideal platform for metal ion application in cancer treatment. Emerging evidence has shown that immunotherapy applied with nanometallic materials may significantly enhance therapeutic efficacy. Here, we focus on the physiopathology of metal ions in tumorigenesis and discuss several breakthroughs regarding the use of nanometallic materials in antitumor immunotherapeutics. These findings demonstrate the prominence of metal ion-based nanomedicine in cancer therapy and prophylaxis, providing many new ideas for basic immunity research and clinical application. Consequently, we provide innovative insights into the comprehensive understanding of the application of metal ions combined with nanomedicine in cancer immunotherapy in the past few years. 

/pdf/metal-ions-and-nanometallic-materials-in-antitumor-immunity-2ycpunxn.pdf

Metal ions and nanometallic materials in antitumor immunity: Function, application, and perspective

Paneth cells are versatile secretory cells located in the crypts of Lieberkühn of the small intestine. In normal conditions, they function as the cornerstones of intestinal health by preserving homeostasis. They perform this function by providing niche factors to the intestinal stem cell compartment, regulating the composition of the microbiome through the production and secretion of antimicrobial peptides, performing phagocytosis and efferocytosis, taking up heavy metals, and preserving barrier integrity. Disturbances in one or more of these functions can lead to intestinal as well as systemic inflammatory and infectious diseases. This review discusses the multiple functions of Paneth cells, and the mechanisms and consequences of Paneth cell dysfunction. It also provides an overview of the tools available for studying Paneth cells.

Paneth cells as the cornerstones of intestinal and organismal health: a primer

Metallobiology of Lactobacillaceae in the gut microbiome.

The cytokine TNF drives inflammatory diseases, e.g., Crohn's disease. In a mouse model of TNF-induced systemic inflammatory response syndrome (SIRS), severe impact on intestinal epithelial cells (IECs) is observed. Zinc confers complete protection in this model. We found that zinc no longer protects in animals which lack glucocorticoids (GCs), or express mutant versions of their receptor GR in IECs, nor in mice which lack gut microbiota. RNA-seq studies in IECs showed that zinc caused reduction in expression of constitutive (STAT1-induced) interferon-stimulated response (ISRE) genes and interferon regulatory factor (IRF) genes. Since some of these genes are involved in TNF-induced cell death in intestinal crypt Paneth cells, and since zinc has direct effects on the composition of the gut microbiota (such as several Staphylococcus species) and on TNF-induced Paneth cell death, we postulate a new zinc-related anti-inflammatory mechanism. Zinc modulates the gut microbiota, causing less induction of ISRE/IRF genes in crypt cells, less TNF-induced necroptosis in Paneth cells, and less fatal evasion of gut bacteria into the system.

https://biblio.ugent.be/publication/8676292/file/8679399.pdf

Zinc inhibits lethal inflammatory shock by preventing microbe-induced interferon signature in intestinal epithelium.

Toxin-producing Corynebacterium ulcerans, a causative agent of diphtheria in humans, was isolated from 53 hedgehogs in Belgium during the spring of 2020. Isolates showed low levels of acquired antimicrobial drug resistance. Strain diversity suggests emergence from an endemic situation. These findings stress the need for raising public awareness and improved wildlife disease surveillance.

/pdf/widespread-disease-in-hedgehogs-erinaceus-europaeus-caused-1nsrwt94sy.pdf

Widespread Disease in Hedgehogs (Erinaceus europaeus) Caused by Toxigenic Corynebacterium ulcerans.

Toxin-producing Corynebacterium ulcerans, causing diphtheria in humans, were isolated from 53 diseased hedgehogs during spring 2020 in Belgium. Isolates showed low levels of acquired antimicrobial resistance. Pronounced strain diversity suggests emergence from an endemic situation. These findings stress the need for raising public awareness and improved wildlife disease surveillance.

/pdf/toxigenic-and-zoonotic-corynebacterium-ulcerans-emerges-from-1x8rze8851.pdf

Serge Verbanck

Papers

Zinc inhibits lethal inflammatory shock by preventing microbe-induced interferon signature in intestinal epithelium.

Widespread Disease in Hedgehogs (Erinaceus europaeus) Caused by Toxigenic Corynebacterium ulcerans.

Toxigenic and zoonotic Corynebacterium ulcerans emerges from widespread hedgehog disease