The use of Trichuris suis and other helminth therapies to treat Crohn’s disease

Reddy, Aditya; Fried, Bernard

doi:10.1007/s00436-006-0416-4

Cited by 48 publications

(37 citation statements)

References 39 publications

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“…Do some GI tracts posses a bacterial community that is suppressive toward pathogenic fungi, a phenomenon seen in the soil ecosystem (Borneman and Becker, 2007)? What are the potential roles eukaryotes may play in immune stimulation and modulation; for example, the role of yeasts and the presence of anti-S-cerevisiae antibodies in Crohn's disease (Schaffer et al, 2007) and the use of certain helminths as a treatment for CD (Reddy and Fried, 2007)?…”

Section: Discussionmentioning

confidence: 99%

Micro-eukaryotic diversity of the human distal gut microbiota: qualitative assessment using culture-dependent and -independent analysis of faeces

2008

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Molecular ecological surveys of the human gut microbiota to date have focused on the prokaryotic fraction of the community and have revealed a remarkable degree of bacterial diversity and functionality. However, there is a dearth of information on the eukaryotic composition of the microbiota, and no culture-independent sequence-based surveys of human faeces are available. Culture-independent analyses based on DNA extraction and polymerase chain reaction targeting both the total eukaryotic 18S rRNA genes and fungal internal transcribed regions (ITS), together with culture-dependent analyses of fungi, were performed on a group of healthy volunteers. Temporal analysis was also included wherever possible. Collectively, the data presented in this study indicate that eukaryotic diversity of the human gut is low, largely temporally stable and predominated by different subtypes of Blastocystis. Specific analyses of the fungal populations indicate that a disparity exists between the cultivable fraction, which is dominated by Candida sp, and cultureindependent analysis, where sequences identical to members of the genera Gloeotinia/Paecilomyces and Galactomyces were most frequently retrieved from both fungal ITS profiles and subsequent clone libraries. Collectively, these results highlight the presence of unprecedented intestinal eukaryotic inhabitants whose functional roles are as yet unknown in healthy individuals. Furthermore, differences between results obtained from traditionally employed culture-based methods and those obtained from culture-independent techniques highlight similar anomalies to that encountered when first analysing the bacterial diversity of the human faecal microbiota using culture-independent surveys.

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Section: Discussionmentioning

confidence: 99%

Micro-eukaryotic diversity of the human distal gut microbiota: qualitative assessment using culture-dependent and -independent analysis of faeces

2008

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“…IL-13 secretion by cells of the innate or adaptive immune system might thus contribute to provide antimicrobial protection, reinforce the mucosal barrier and maintain host-microbial homeostasis. The described effect might contribute to the clinical success of helminth therapy in patients with Crohn's disease [54]. On the other hand, reduced mucosal IL-13 levels in the absence of continuous Th2-mediated immune stimulation due to improved hygiene conditions and a lower prevalence of helminth infections in industrialized countries might lead to alterations in the enteric microbiota, particularly of the infant population, and in turn predispose to inflammatory and autoimmune diseases [55,56].…”

Section: Discussionmentioning

confidence: 99%

Interleukin-13-Mediated Paneth Cell Degranulation and Antimicrobial Peptide Release

et al. 2014

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Paneth cell-derived enteric antimicrobial peptides significantly contribute to antibacterial host defense and host-microbial homeostasis. Regulation occurs by enzymatic processing and release into the small intestinal lumen, but the stimuli involved are incompletely understood. Here, the capacity of various microbial and immune stimuli to induce antimicrobial peptide release from small intestinal tissue was systematically evaluated using antibacterial activity testing, immunostaining for Paneth cell granules and mass spectrometry. We confirmed the stimulatory activity of the muscarinic receptor agonist carbachol and the nucleotide-binding oligomerization domain ligand muramyl dipeptide. In contrast, no release of antibacterial activity was noted after treatment with the Toll-like receptor ligands poly(I:C), lipopolysaccharide or CpG, and the cytokines interleukin (IL)-15, IL-22, IL-28 and interferon-γ. Rapid Paneth cell degranulation and antimicrobial activity release, however, was observed after stimulation with the endogenous mediators IL-4 and IL-13. This process required phosphatidylinositol 3-kinase and was associated with protein kinase B phosphorylation in Paneth cells. Flow cytometric analysis confirmed expression of the IL-13 receptor α1 on isolated Paneth cells. Our findings identify a novel role of IL-13 as inducer of Paneth cell degranulation and enteric antimicrobial peptide release. IL-13 may thus contribute to mucosal antimicrobial host defense and host microbial homeostasis.

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“…Secondly, the lack of helminth induced immunomodulation in the human populations of the industrialised countries has been hypothesised to contribute to the steep increase in autoimmune diseases, such as inflammatory bowel disease, type 1 diabetes, and multiple sclerosis (reviewed by McKay, 2006;Elliott et al, 2007;Zaccone et al, 2007;Fleming, 2011). This 'Helminth Hypothesis' (Elliott et al, 2007) is derived from the original 'Hygiene Hypothesis' of Strachan (1989), and T. suis is one of the favourites for potential medical use (Reddy and Fried, 2007). T. suis was, among other criteria, originally selected because the infections are self-eliminating in man and the larvae are non-migratory (Elliott et al, 2007).…”

Section: Immune Responses and Immunomodulationmentioning

confidence: 99%

Helminth parasites in pigs: New challenges in pig production and current research highlights

Roepstorff

Mejer

Nejsum

et al. 2011

Veterinary Parasitology

148

101

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a b s t r a c tHelminths in pigs have generally received little attention from veterinary parasitologists, despite Ascaris suum, Trichuris suis, and Oesophagostomum sp. being common worldwide. The present paper presents challenges and current research highlights connected with these parasites.In Danish swine herds, new indoor production systems may favour helminth transmission and growing knowledge on pasture survival and infectivity of A. suum and T. suis eggs indicates that they may constitute a serious threat to outdoor pig production. Furthermore, it is now evident that A. suum is zoonotic and the same may be true for T. suis. With these 'new' challenges and the economic impact of the infections, further research is warranted. Better understanding of host-parasite relationships and A. suum and T. suis egg ecology may also improve the understanding and control of human A. lumbricoides and T. trichiura infections.The population dynamics of the three parasites are well documented and may be used to study phenomena, such as predisposition and worm aggregation. Furthermore, better methods to recover larvae have provided tools for quantifying parasite transmission. Thus, an on-going study using helminth naïve tracer pigs has surprisingly demonstrated that soil infectivity with A. suum and T. suis increases during the first 2-3 years after pasture contamination.Though all three helminth species stimulate the Th2 arm of the immune system, Oesophagostomum seems weakly immunogenic, perhaps via specific modulation of the host immune system. A. suum and T. suis potently modulate the host immune response, up-regulating Th2 and down-regulating Th1. As a consequence, A. suum may compromise the efficacy of certain bacterial vaccines, whereas T. suis, which establish only short-term in humans, is a favourite candidate for down-regulating autoimmune Th1-related diseases in man.Some basic research findings have offered new possibilities for future sustainable control measures. For example, the heredity of host resistance to A. suum and T. suis is so high that breeding for resistant pigs may be a possibility. Experimental studies have demonstrated that fermentable dietary carbohydrates have an antagonistic effect on Oesophagostomum and to a lesser extent on T. suis and A. suum, whereas egg-destroying microfungi may be used to inactivate the hard-shelled A. suum and T. suis eggs in the environment.Helminth control in Denmark has previously relied solely on anthelmintic treatment in herds with low helminth transmission. When indoor transmission rates * Corresponding author. Tel.: +45 3533 2746. increase, or in outdoor herds with high pasture contamination levels, medication may advantageously be combined with sustainable control measures, such as selected pig genomes, bioactive forages, and egg-destroying microfungi.

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The use of Trichuris suis and other helminth therapies to treat Crohn’s disease

Cited by 48 publications

References 39 publications

Micro-eukaryotic diversity of the human distal gut microbiota: qualitative assessment using culture-dependent and -independent analysis of faeces

Micro-eukaryotic diversity of the human distal gut microbiota: qualitative assessment using culture-dependent and -independent analysis of faeces

Interleukin-13-Mediated Paneth Cell Degranulation and Antimicrobial Peptide Release

Helminth parasites in pigs: New challenges in pig production and current research highlights

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