Intestinal antimicrobial peptides during homeostasis, infection, and disease

Department of Medicine, Immunology Institute, Mount Sinai School of Medicine New York, NY, USA.
Frontiers in Immunology 10/2012; 3:310. DOI: 10.3389/fimmu.2012.00310
Source: PubMed


Antimicrobial peptides (AMPs), including defensins and cathelicidins, constitute an arsenal of innate regulators of paramount importance in the gut. The intestinal epithelium is exposed to myriad of enteric pathogens and these endogenous peptides are essential to fend off microbes and protect against infections. It is becoming increasingly evident that AMPs shape the composition of the commensal microbiota and help maintain intestinal homeostasis. They contribute to innate immunity, hence playing important functions in health and disease. AMP expression is tightly controlled by the engagement of pattern recognition receptors (PRRs) and their impairment is linked to abnormal host responses to infection and inflammatory bowel diseases (IBD). In this review, we provide an overview of the mucosal immune barriers and the intricate crosstalk between the host and the microbiota during homeostasis. We focus on the AMPs and pay particular attention to how PRRs promote their secretion in the intestine. Furthermore, we discuss their production and main functions in three different scenarios, at steady state, throughout infection with enteric pathogens and IBD.

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Available from: Garabet Yeretssian, May 25, 2014
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    • "In particular, it is reported that immune " sensors " play an important role in nutrients metabolism, gut microbiome and intestinal immune system. For example, the induced host intestinal antimicrobial defense peptides showed comprehensive biological functions and therapeutic applications [6] [7]. "
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    ABSTRACT: Gastrointestine is a complex ecosystem which plays a critical role in nutrients digestion and absorption. Exoge-nous natural proteins in food and feed will be degraded into short-chain peptides and amino acids by various prote-ase, and then be adsorbed by transporters in intestine, which is also well-known as " internalization ". During the process, the intestinal barrier, containing at least intestinal microbiota and tight junction proteins, is very important to prevent invasion of bacteria, viruses, fungi and heterologous proteins [1]. The diversity and the composition of the intestinal microbiota, exhibit an irreplaceable role in the maintenance of intestinal homeostasis. Tight junction proteins are key molecules for determination of the intestinal permeability [2]. It is reported that many exogenous peptides have important physiological functions after degradation, such as nutrient stress and specific immune responses. For example, the peptides from soybean antigen proteins can induced intestinal sensitization, and lead to diarrhea. However, in general it is still unclear what is the nature of the exoge-nous natural peptides or mucosal factors that affect the intestinal microbiota and the tight junction proteins function. Interestingly, the host gut has evolved corresponding patterns for the utility and metabolism of exogenous bioactive peptides, such as ubiquitin-proteasome system and autophagosome system. Some key actors are confirmed to take part in the interplay between autophagy and ubiquitin/proteasome catabolic pathways [3, 4]. Many important signaling pathways have been documented to be involved in the regulation of the " internaliza-tion " process of the exogenous bioactive peptides, as well as intestinal innate immune responses, particularly NF-κB pathway, PXR pathway and Barkor/Beclin 1 pathway [5]. In particular, it is reported that immune " sensors " play an important role in nutrients metabolism, gut microbiome and intestinal immune system. For example, the induced host intestinal antimicrobial defense peptides showed comprehensive biological functions and therapeutic applications [6, 7]. Except for the local gastrointestinal modulation, it is reported that the intestinal gut-brain-endocrine-immune axis performs a systemic modulation of exogenous natural proteins and bioactive peptides. As an important part to convert the material and energy metabolism of the body, the intestinal absorption and barrier function are strictly controlled and modulated by the central nervous system, including the nervous, endocrine and immune network [8, 9]. This special issue " advance of interactions between exogenous natural bioactive peptides and intestinal barrier and immune responses " collects and provides an overview of the current understanding of interaction between ex-ogenous natural bioactive peptides and intestinal barrier and immune responses, particularly the critical signal pathways, which will shed light on how the exogenous protein/peptides be metabolized and utilized via gastrointes-tinal system. Future studies will be performed to reveal the potential mechanisms.
    Current Protein and Peptide Science 06/2015; 16(5):297-343. DOI:10.2174/138920371607150810124927 · 3.15 Impact Factor
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    • "defensins, cathelicidins) that are found in the inner mucus layer. If a pathogen breaks through the mucus layer, there is loss of homeostasis and disruption of gut barrier integrity( 98 ). "
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    ABSTRACT: The present report describes the presentations delivered at the 7th International Yakult Symposium, 'The Intestinal Microbiota and Probiotics: Exploiting Their Influence on Health', in London on 22-23 April 2013. The following two themes associated with health risks were covered: (1) the impact of age and diet on the gut microbiota and (2) the gut microbiota's interaction with the host. The strong influence of the maternal gut microbiota on neonatal colonisation was reported, as well as rapid changes in the gut microbiome of older people who move from community living to residential care. The effects of dietary changes on gut metabolism were described and the potential influence of inter-individual microbiota differences was noted, in particular the presence/absence of keystone species involved in butyrate metabolism. Several speakers highlighted the association between certain metabolic disorders and imbalanced or less diverse microbiota. Data from metagenomic analyses and novel techniques (including an ex vivo human mucosa model) provided new insights into the microbiota's influence on coeliac, obesity-related and inflammatory diseases, as well as the potential of probiotics. Akkermansia muciniphila and Faecalibacterium prausnitzii were suggested as targets for intervention. Host-microbiota interactions were explored in the context of gut barrier function, pathogenic bacteria recognition, and the ability of the immune system to induce either tolerogenic or inflammatory responses. There was speculation that the gut microbiota should be considered a separate organ, and whether analysis of an individual's microbiota could be useful in identifying their disease risk and/or therapy; however, more research is needed into specific diseases, different population groups and microbial interventions including probiotics.
    British Journal Of Nutrition 07/2014; 112 Suppl 1(Suppl 1):S1-S18. DOI:10.1017/S0007114514001275 · 3.45 Impact Factor
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    • "ls , can pro - tect against a wide array of infectious agents , such as bac - teria , fungi , parasites , viruses , and cancer cells ( Li et al . , 2012 ; Tang et al . , 2009 , 2010 ) . It is becoming increasingly accepted that antimicrobial peptides shape the composi - tion of the commensal microbiota and help to maintain intestinal homeostasis ( Muniz et al . , 2012 ) . Dietary sup - plementation with the antimicrobial peptide lactoferrin can improve intestinal microflora in weaned piglets ( Tang et al . , 2012 ) . Wang et al . ( 2006 ) demonstrated that pigs supplemented with lactoferrin had greater villi height and lower crypt depth at the small intestinal mucosa , which may contribute to improve"
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    ABSTRACT: Deoxynivalenol (DON) affects animal and human health and targets the gastrointestinal tract. The objective of this study was to evaluate the ability of composite antimicrobial peptides (CAP) to repair intestinal injury in piglets challenged with DON. A total of 28 piglets (Duroc x Landrace x Large Yorkshire) weaned at 28 d of age were randomly assigned to receive 1 of 4 treatments (7 pigs/treatment): negative control, basal diet (NC), basal diet + 0.4% composite antimicrobial peptide (CAP), basal diet + 4 ppm DON (DON), and basal diet + 4 ppm DON + 0.4% CAP (DON + CAP). After an adaptation period of 7 d, blood samples were collected on d 15 and 30 after the initiation of treatment for determinations of the concentrations of D-lactate and diamine oxidase. At the end of the study, all piglets were slaughtered to obtain small intestines for the determination of intestinal morphology, epithelial cell proliferation, and protein expression in the mammalian target of rapamycin (mTOR) signaling pathway. The results showed that DON increased serum levels of D-lactate and diamine oxidase, and these values in the CAP and DON + CAP treatments were lower than those in the NC and DON treatments, respectively (P < 0.05). The villous height/crypt depth in the jejunum and ileum and the goblet cell number in the ileum in the CAP and DON + CAP treatments were greater than those in the NC and DON treatments (P < 0.05). The proliferating cell nuclear antigen (PCNA) labeling indexes for the jejunum and ileum in the DON + CAP treatment were greater than those in the DON treatment (P < 0.05). The DON decreased (P < 0.05) the relative protein expression levels of phosphorylated Akt (Protein Kinase B) and mTOR in the jejunal and ileal mucosa and of phosphorylated 4E-binding protein 1 (p-4EBP1) in the jejunal mucosa, while CAP increased (P < 0.05) the protein expression levels of p-4EBP1 in the jejunum. These findings showed that DON could enhance intestinal permeability, damage villi, cause epithelial cell apoptosis and inhibit protein synthesis, whereas CAP improved intestinal morphology and promoted intestinal epithelial cell proliferation and protein synthesis, indicating that CAP may repair the intestinal injury induced by DON.
    Journal of Animal Science 08/2013; 91(10). DOI:10.2527/jas.2013-6427 · 2.11 Impact Factor
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