The potential for immunoglobulins and host defense peptides (HDPs) to reduce the use of antibiotics in animal production

Dijk, Albert van; Hedegaard, Chris Juul; Haagsman, Henk P.; Heegaard, Peter M. H.

doi:10.1186/s13567-018-0558-2

Cited by 33 publications

(31 citation statements)

References 118 publications

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“…Host defence peptides (HDPs) are produced by intestinal epithelial cells and phagocytes in the gastrointestinal tract. As the most important HDPs in pigs, pBDs play important roles in the body's response to infection and inflammation (van Dijk, Hedegaard, Haagsman, & Heegaard, 2018;Hancock, Haney, & Gill, 2016;Nijnik & Hancock, 2009). Previous evidence demonstrated that some probiotics such as L. reuteri, L. salivarius and Bacillus subtilis contribute to the increased levels of pBDs in intestinal tissue (Deng, Li, Zhang, & Yang, 2013;Liu et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Effects of Lactobacillus plantarum on the intestinal morphology, intestinal barrier function and microbiota composition of suckling piglets

Wang

Sun

et al. 2019

Animal Physiology Nutrition

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This study investigated the effect of Lactobacillus plantarum strain 299v on gut health in suckling piglets. Sixty newborn piglets were assigned to control and probiotic treatments, with three litters per treatment (ten piglets/litter). From days 1 to 20 of life, piglets were orally administered a placebo of 0.1% peptone or 1.0 × 1010 CFU L. plantarum 299v daily. Six piglets per treatment were sacrificed on day 20, and intestinal tissues (including duodenum, jejunum, ileum and colon) and the intestinal contents from colon segments were collected. The results demonstrated that piglets treated with L. plantarum 299v had a lower diarrhoea incidence than the controls. L. plantarum 299v administration significantly increased the ratio of the villus height to the crypt depth in the jejunum and ileum, as well as the mRNA expression of jejunal occludin and ileal zonula occludens 1 (ZO‐1). The L. plantarum treatment also increased the mRNA abundance of porcine β‐defensin 2 (pBD2) and pBD3 in the jejunum and ileum and of toll‐like receptors (TLRs), such as TLR2, TLR4, TLR6 and TLR9 in the ileum, and significantly upregulated the mRNA abundances of ileal pBD1 and colonic TLR4. Additionally, the L. plantarum 299v treatment significantly changed the structure of the colonic microbiota, as evidenced by the obvious increases in the relative abundances of the phyla Firmicutes and Actinobacteria and of the genus Lactobacillus. Our findings indicate that L. plantarum 299v facilitates the gut health of suckling piglets, probably by improving the intestinal morphology and intestinal barrier function and by modifying the structure of the gut microbiota.

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Section: Discussionmentioning

confidence: 99%

Effects of Lactobacillus plantarum on the intestinal morphology, intestinal barrier function and microbiota composition of suckling piglets

Wang

Sun

et al. 2019

Animal Physiology Nutrition

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“…A recent notable study in current clinical development is the use of silicone hydrogel contact lenses coated with a synthetic immunomodulatory peptide Mel4 to reduce contact lensassociated infections and inflammation 249 . Notably, the potential therapeutic and prophylactic success of immunomodulatory CHDP-derived peptides as alternatives to antibiotics in veterinary medicine may pave the way for clinical trials in humans (One Health approach) 250 .…”

Section: [H3] Clinical Trialsmentioning

confidence: 99%

Antimicrobial host defence peptides: functions and clinical potential

Mookherjee

Anderson

Haagsman

et al. 2020

Nat Rev Drug Discov

Self Cite

976

955

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Cationic host defence peptides (CHDP), also known as antimicrobial peptides, are naturally-occurring peptides which can combat infections through their direct microbicidal properties and/or by influencing the host's immune responses. The unique ability of CHDP to control infections as well as resolve harmful inflammation has generated interest in harnessing the properties of these peptides to develop new therapies for infectious diseases, chronic inflammatory disorders and wound healing. Various strategies have been employed to design synthetic optimized peptides, with negligible toxicity. Here, we focus on the progress made in understanding the scope of functions of CHDP and the emerging potential clinical applications of CHDP-based therapies. This has led to the adoption of the current name for this family of peptides, Cationic Host Defence Peptides, which encompasses the wide range of described functions. Over the last three decades there has been substantial interest in therapeutically harnessing CHDP, with more than 5000 papers published in this area of research since 2017 alone. These include the examination of potential clinical uses for CHDP ranging from infections including multidrug-resistant bacteria 16-19 , to chronic inflammatory diseases such as arthritis 20 , asthma 21 and colitis 22 , as well as some cancers 23. Peptide-based therapeutics currently in clinical trials are primarily for the treatment of infections such as respiratory, oral and catheter-related infections, and for wound healing (see http://dramp.cpu-bioinfor.org/browse/ClinicalTrialsData.php). This review will provide an overview of current understanding of the scope of functions of CHDP, primarily from eukaryotes. Emerging therapeutic applications of these peptides, current clinical trials and the associated clinical developmental challenges will be discussed. Although there is increasing interest in the development of non-peptide mimics of CHDP for therapeutic application, such as peptoid analogs (reviewed in 24), a comprehensive discussion of these approaches is beyond the scope of this review. [H1] Naturally occurring CHDP The antimicrobial peptide database has catalogued more than 2600 natural antimicrobial peptides, including those annotated as immunomodulatory 25. The major families of CHDP from eukaryotes that are of interest from a drug discovery perspective are summarized below. [H2] Vertebrate CHDP CHDP from vertebrates have an essential role in the first line of defense against microbial pathogens. Upon infection, CHDP can kill pathogens through diverse mechanisms 26-31 (discussed below), acting rapidly and directly on the pathogen when present in high local concentrations, or indirectly to modify components of host defense. These peptides exhibit immunomodulatory activities that can be either pro-or anti-inflammatory depending on the phase of the infection (see below) 12-14,29. CHDP from vertebrates are amphipathic peptides containing amino acids with hydrophilic and hydrophobic side chains at opposite sides of the molec...

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“…1,25(OH) 2 D 3 -dependent induction of autophagy was initially discovered in immune cells. 1,25(OH) 2 D 3 triggers autophagy in immune cells for eradication of bacteria through the host defence peptide LL-37 [ 156 ].…”

Section: Vitamin D Signaling Within Tumour Cellsmentioning

confidence: 99%

Vitamin D Signaling in Inflammation and Cancer: Molecular Mechanisms and Therapeutic Implications

2020

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Vitamin D and its active metabolites are important nutrients for human skeletal health. UV irradiation of skin converts 7-dehydrocholesterol into vitamin D3, which metabolized in the liver and kidneys into its active form, 1α,25-dihydroxyvitamin D3. Apart from its classical role in calcium and phosphate regulation, scientists have shown that the vitamin D receptor is expressed in almost all tissues of the body, hence it has numerous biological effects. These includes fetal and adult homeostatic functions in development and differentiation of metabolic, epidermal, endocrine, neurological and immunological systems of the body. Moreover, the expression of vitamin D receptor in the majority of immune cells and the ability of these cells to actively metabolize 25(OH)D3 into its active form 1,25(OH)2D3 reinforces the important role of vitamin D signaling in maintaining a healthy immune system. In addition, several studies have showed that vitamin D has important regulatory roles of mechanisms controlling proliferation, differentiation and growth. The administration of vitamin D analogues or the active metabolite of vitamin D activates apoptotic pathways, has antiproliferative effects and inhibits angiogenesis. This review aims to provide an up-to-date overview on the effects of vitamin D and its receptor (VDR) in regulating inflammation, different cell death modalities and cancer. It also aims to investigate the possible therapeutic benefits of vitamin D and its analogues as anticancer agents.

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The potential for immunoglobulins and host defense peptides (HDPs) to reduce the use of antibiotics in animal production

Cited by 33 publications

References 118 publications

Effects of Lactobacillus plantarum on the intestinal morphology, intestinal barrier function and microbiota composition of suckling piglets

Effects of Lactobacillus plantarum on the intestinal morphology, intestinal barrier function and microbiota composition of suckling piglets

Antimicrobial host defence peptides: functions and clinical potential

Vitamin D Signaling in Inflammation and Cancer: Molecular Mechanisms and Therapeutic Implications

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