Immune cells and microbiota response to iron starvation

Metal ions are essential for life on Earth, mostly as crucial components of all living organisms; indeed, they are necessary for bioenergetics functions as crucial redox catalysts. Due to the essential role of iron in biological processes, body iron content is finely regulated and is the battlefield of a tug-of-war between the host and the microbiota.Iron availability in the intestinal lumen could prevent or promote intestinal dysbiosis, although current data do not provide a definitive response. Recent data demonstrated that nutritional derived polyphenols explicit their anti-inflammatory functions sequestrating iron from immune cells. Here, we discuss whether nutritional iron chelators could be able to change the gut microbiota composition and prevent the intestinal dysbiosis associated with intestinal chronic inflammatory syndromes.Iron is lost by cellular exfoliation and occasional bleeding; it is absorbed from nutritional components. Heme is the most important source of dietary iron, while non-heme iron can be absorbed only in the duodenum and the beginning of the jejunum in pH permissive (acid) conditions. Western diets often contain large quantities of foods characterized by a high heme-iron content like meat, fish, and poultry, and small quantities of non-heme-iron content like vegetables, fruits, and nuts. Furthermore, nutritional substances can affect iron absorption: ascorbic acid is an efficient enhancer of non-heme-iron absorption, vice versa, phytic acid is known to be among the major iron absorption inhibitors, and iron-chelating substances like quercetin inhibit its absorption, likely due to loss of chelated-iron solubility.Iron deficiency is the most common cause of anemia worldwide and one of the most common complications observed in inflammatory bowel disease (IBD) patients due to gastrointestinal hemorrhages. In IBD patients, the guidelines for the management of iron deficiency are not entirely satisfactory because following oral iron supplementation patients sometimes report worsening of the IBD symptoms (1). Interestingly, iron supplemented diets can also show protective effects in dextran sodium sulfate (DSS)-induced colitis models. Constante et al. demonstrated that iron formulation dramatically changed the outcome of the DSS-induced colitis, as oral supplementation with ferrous bisglycinate but not ferric ethylenediaminetetraacetic acid enhanced the beneficial action of probiotics (2)

Messages from the inside. The dynamic environment that favors intestinal homeostasis

An organism is defined as "an individual living thing capable of responding to stimuli, growing, reproducing, and maintaining homeostasis." Early during evolution multicellular organisms explored the advantages of a symbiotic life. Mammals harbor a complex aggregate of microorganisms (called microbiota) that includes bacteria, fungi, and archaea. Some of these bacteria have already defined beneficial roles for the human host that include the ability to break down nutrients that could not otherwise be digested, preventing the growth of harmful species, as well as the ability to produce vitamins or hormones. It is intuitive that along the evolutionary path several mechanisms favored bacteria that provided advantages to the host which, in return, avoided launching an aggressive immunological response against them. The intestinal immunological response does not ignore the lumenal content, on the contrary, immune surveillance is favored by continuous antigen sampling. Some intestinal epithelial cells (ECs) are crucial during the sampling process, others actively participate in the defense mechanism. In essence the epithelium acts as a traffic light, communicating to the inside world whether conditions are safe or dangerous, and thus influencing immunological response. In this review we will discuss the dynamic factors that act on the intestinal ECs and how they directly or indirectly influence immune cells during states of health and disease. © 2013 Eri and Chieppa

Looking at flavonoid biodiversity in horticultural crops: A colored mine with nutritional benefits

Flavonoids represent a wide group of plant secondary metabolites implicated in many physiological roles, from the attraction of pollinators to the protection against biotic or abiotic stresses. Flavonoids are synthetized in a number of horticultural crops that are important components of our daily diet. In the last decades, the consumption of vegetables rich in antioxidants has been strongly promoted from the perspective of prevention/protection against chronic diseases. Therefore, due to their nutritional importance, several attempts have been made to enhance flavonoid levels in species of agronomic interest. In this review, we focus on the flavonoid biodiversity among the major horticultural species, which is responsible of differences among closely related species and influences the qualitative/quantitative composition. We also review the role of flavonoids in the nutritional quality of plant products, contributing to their organoleptic and nutritional properties, and the main strategies of biofortification to increase their content

Intestinal epithelium and autophagy: Partners in gut homeostasis

One of the most significant challenges of cell biology is to understand how each type of cell copes with its specific workload without suffering damage. Among the most intriguing questions concerns intestinal epithelial cells in mammals; these cells act as a barrier between the internally protected region and the external environment that is exposed constantly to food and microbes. A major process involved in the processing of microbes is autophagy. In the intestine, through multiple, complex signaling pathways, autophagy including macroautophagy and xenophagy is pivotal in mounting appropriate intestinal immune responses and anti-microbial protection. Dysfunctional autophagy mechanism leads to chronic intestinal inflammation, such as inflammatory bowel disease (IBD). Studies involving a number of in vitro and in vivo mouse models in addition to human clinical studies have revealed a detailed role for autophagy in the generation of chronic intestinal inflammation. A number of genome-wide association studies identified roles for numerous autophagy genes in IBD, especially in Crohn's disease. In this review, we will explore in detail the latest research linking autophagy to intestinal homeostasis and how alterations in autophagy pathways lead to intestinal inflammation. © 2013 Randall-Demllo, Chieppa and Eri

Beyond just bacteria: Functional biomes in the gut ecosystem including virome, mycobiome, archaeome and helminths

Gut microbiota refers to a complex network of microbes, which exerts a marked influenceon the host’s health. It is composed of bacteria, fungi, viruses, and helminths. Bacteria, or collectively,the bacteriome, comprises a significant proportion of the well-characterized microbiome. However,the other communities referred to as ‘dark matter’ of microbiomes such as viruses (virome), fungi(mycobiome), archaea (archaeome), and helminths have not been completely elucidated. Developmentof new and improved metagenomics methods has allowed the identification of complete genomesfrom the genetic material in the human gut, opening new perspectives on the understanding ofthe gut microbiome composition, their importance, and potential clinical applications. Here, wereview the recent evidence on the viruses, fungi, archaea, and helminths found in the mammalian gut,detailing their interactions with the resident bacterial microbiota and the host, to explore the potentialimpact of the microbiome on host’s health. The role of fecal virome transplantations, pre-, pro-, andsyn-biotic interventions in modulating the microbiome and their related concerns are also discussed

Engagement of the Mannose Receptor by Tumoral Mucins Activates an Immune Suppressive Phenotype in Human Tumor-Associated Macrophages

Tumor-Associated Macrophages (TAMs) are abundantly present in the stroma of solid tumors and modulate several important biological processes, such as neoangiogenesis, cancer cell proliferation and invasion, and suppression of adaptive immune responses. Myeloid C-type lectin receptors (CLRs) constitute a large family of transmembrane carbohydrate-binding receptors that recognize pathogens as well as endogenous glycoproteins. Several lines of evidence demonstrate that some CLRs can inhibit the immune response. In this study we investigated TAM-associated molecules potentially involved in their immune suppressive activity. We found that TAMs isolated from human ovarian carcinoma samples predominantly express the CLRs Dectin-1, MDL-1, MGL, DCIR, and most abundantly the Mannose Receptor (MR). Components of carcinomatous ascites and purified tumoral mucins (CA125 and TAG-72) bound the MR and induced its internalization. MR engagement by tumoral mucins and by an agonist anti-MR antibody modulated cytokine production by TAM toward an immune-suppressive profile: increase of IL-10, absence of IL-12, and decrease of the Th1-attracting chemokine CCL3. This study highlights that tumoral mucin-mediated ligation of the MR on infiltrating TAM may contribute to their immune suppressive phenotype

Selection of tomato landraces with high fruit yield and nutritional quality under elevated temperatures

BACKGROUND: Global warming and extreme or adverse events induced by climatic fluctuations are an important threat for plants growth and agricultural production. Adaptability to environmental changes prevalently derives from a large set of genetic traits affecting physiological and agronomic parameters. Therefore, the identification of genotypes that are good yield performer at high temperatures is becoming increasingly necessary for future breeding programs. Here, we analyzed the performances of different tomato landraces grown under elevated temperatures in terms of yield and nutritional quality of the fruit. Finally, we evaluated the antioxidant and anti-inflammatory activities of fruit extracts from the tomato landraces selected. RESULTS: The tomato landraces analyzed here in a hot climate differed in terms of yield performance, physicochemical parameters of fruit (pH, titratable acidity, degrees Brix, firmness), bioactive compounds (ascorbic acid, carotenoids, and polyphenols), and anti-inflammatory potential. Three of these landraces (named E30, E94, and PDVIT) showed higher fruit quality and nutritional value. An estimated evaluation index allowed identification of PDVIT as the best performer in terms of yield and fruit quality under high temperatures. CONCLUSION: The analyses performed here highlight the possibility to identify new landraces that can combine good yield performances and fruit nutritional quality at high temperatures, information that is useful for future breeding programs. © 2020 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry

Bioavailable Citrus sinensis extract: Polyphenolic composition and biological activity

Citrus plants contain large amounts of flavonoids with beneficial effects on human health. In the present study, the antioxidant and anti-inflammatory potential of bioavailable polyphenols from Citrus sinensis was evaluated in vitro and ex vivo, using the murine macrophages cell line J774A.1 and primary peritoneal macrophages. Following simulated gastro-intestinal digestion, the in vitro bioavailability of Citrus sinensis polyphenolic extract was assessed using the human cell line Caco-2 grown as monolayers on a transwell membrane. Data demonstrated a relative permeation of its compounds (8.3%). Thus, the antioxidant and anti-inflammatory effect of polyphenolic Citrus sinensis fraction (Cs) was compared to the bioavailable one (CsB). Results revealed that Citrus extract were able to reduce macrophages pro-inflammatory mediators, including nitric oxide, iNOS, COX-2 and different cytokines. Moreover, the effect of Citrus sinensis polyphenols was associated with antioxidant effects, such as a reduction of reactive oxygen species (ROS) and heme-oxygenase-1 (HO-1) increased expression. Our results provide evidence that the bioavailable polyphenolic constituents of the Citrus sinensis extract accumulate prevalently at intestinal level and could reach systemic circulation exerting their effect. The bioavailable fraction showed a higher anti-inflammatory and antioxidant potential compared to the initial extract, thus highlighting its potential nutraceutical value

Production of the soluble pattern recognition receptor PTX3 by myeloid, but not plasmacytoid, dendritic cells

PTX3 is a prototypic of long pentraxin consisting of an N-terminal portion coupled to a C-terminal pentraxin domain, the latter related to short pentraxins (C-reactive protein and serum amyloid P component). PTX3 is a soluble pattern recognition receptor, which plays a non-redundant role in resistance against selected pathogens and in female fertility. The present study was designed to analyze the production of PTX3 by human dendritic cells (DC) and to define the role of different innate immunity receptors in its induction. Human monocyte-derived DC produced copious amounts of PTX3 in response to microbial ligands engaging different members of the Toll-like receptor (TLR) family (TLR1 through TLR6), whereas engagement of the mannose receptor had no substantial effect. DC were better producers of PTX3 than monocytes and macrophages. Freshly isolated peripheral blood myeloid DC produced PTX3 in response to diverse microbial stimuli. In contrast, plasmacytoid DC exposed to influenza virus or to CpG oligodeoxynucleotides engaging TLR9, did not produce PTX3. PTX3-expressing DC were present in inflammatory lymph nodes from HIV-infected patients. These results suggest that DC of myelomonocytic origin are a major source of PTX3, a molecule which facilitates pathogen recognition and subsequent activation of innate and adaptive immunity