Effect of experimental hookworm infection on insulin resistance in people at risk of type 2 diabetes.

The reduced prevalence of insulin resistance and type 2 diabetes in countries with endemic parasitic worm infections suggests a protective role for worms against metabolic disorders, however clinical evidence has been non-existent. This 2-year randomised, double-blinded clinical trial in Australia of hookworm infection in 40 male and female adults at risk of type 2 diabetes assessed the safety and potential metabolic benefits of treatment with either 20 (n = 14) or 40 (n = 13) Necator americanus larvae (L3) or Placebo (n = 13) (Registration ACTRN12617000818336). Primary outcome was safety defined by adverse events and completion rate.

Randomized, Placebo Controlled Trial of Experimental Hookworm Infection for Improving Gluten Tolerance in Celiac Disease.

Introduction: Celiac disease is an autoimmune disorder where intestinal immunopathology arises after gluten consumption. Previous studies suggested that hookworm infection restores gluten tolerance; however, these studies were small (n = 12) and not placebo controlled.

Methods: We undertook a randomized, placebo-controlled trial of hookworm infection in 54 people with celiac disease.

Safety and tolerability of experimental hookworm infection in humans with metabolic disease: study protocol for a phase 1b randomised controlled clinical trial.

Background: Abdominal obesity and presence of the metabolic syndrome (MetS) significantly increase the risk of developing diseases such as Type 2 diabetes mellitus (T2DM) with escalating emergence of MetS and T2DM constituting a significant public health crisis worldwide. Lower prevalence of inflammatory and metabolic diseases such as T2DM in countries with higher incidences of helminth infections suggested a potential role for these parasites in the prevention and management of certain diseases. Recent studies confirmed the potential protective nature of helminth infection against MetS and T2DM via immunomodulation or, potentially, alteration of the intestinal microbiota.

The NLRP3 Inflammasome Suppresses Protective Immunity to Gastrointestinal Helminth Infection.

Inflammasomes promote immunity to microbial pathogens by regulating the function of IL-1-family cytokines such as IL-18 and IL-1β. However, the roles for inflammasomes during parasitic helminth infections remain unclear. We demonstrate that mice and humans infected with gastrointestinal nematodes display increased IL-18 secretion, which in Trichuris-infected or worm antigen-treated mice and in macrophages co-cultured with Trichuris antigens or exosome-like vesicles was dependent on the NLRP3 inflammasome.

Sessile Serrated Adenomas in Young Patients may have Limited Risk of Malignant Progression.

Goals: To provide preliminary evidence that sessile serrated adenomas (SSA) are low-risk polyps in young patients.

Background: SSAs are the dominant polyp of the serrated neoplasia pathway and as such are the precursor of up to 20% of colorectal carcinomas (CRC). Up to 90% of these cancers are expected to harbor a BRAF mutation.

Suppression of inflammation and tissue damage by a hookworm recombinant protein in experimental colitis.

Gastrointestinal parasites, hookworms in particular, have evolved to cause minimal harm to their hosts when present in small numbers, allowing them to establish chronic infections for decades. They do so by creating an immunoregulatory environment that promotes their own survival, but paradoxically also benefits the host by protecting against the onset of many inflammatory diseases. To harness the therapeutic value of hookworms without using live parasites, we have examined the protective properties of the recombinant protein anti-inflammatory protein (AIP)-1, secreted in abundance by hookworms within the intestinal mucosa, in experimental colitis.

Split-dose bowel preparation with polyethylene glycol for colonoscopy performed under propofol sedation. Is there an optimal timing?

Objective: Aspiration risk, especially with propofol sedation, remains a concern after split-dose bowel preparation of up to 1 L polyethylene glycol for the procedure. We aimed to identify the ideal timing of bowel preparation to achieve optimal colon cleansing with no increased risk of aspiration.

Methods: A total of 892 consecutive patients undergoing simultaneous esophagogastroduodenoscopy (EGD) and colonoscopy were prospectively recruited.

Hookworm infection.

Hookworms are soil-transmitted nematode parasites that can reside for many years in the small intestine of their human hosts; Necator americanus is the predominant infecting species. Adult worms feed on the blood of a host and can cause iron deficiency anaemia, especially in high-risk populations (children and women of childbearing age). Almost 500 million people in developing tropical countries are infected, and simulation models estimate that hookworm infection is responsible for >4 million disability-adjusted life years lost annually.

High prevalence of sessile serrated adenomas in contemporary outpatient colonoscopy practice.

Background: Sessile serrated adenomas (SSA) are the polyp precursor of 15-20% of colorectal carcinomas. There is debate about their prevalence and increasing discussion about the need for a serrated polyp detection rate as a quality indicator for colonoscopy.

Aims: To assess the prevalence of SSA at an outpatient gastroenterology service.

Changes in duodenal tissue-associated microbiota following hookworm infection and consecutive gluten challenges in humans with coeliac disease.

A reduced diversity of the gastrointestinal commensal microbiota is associated with the development of several inflammatory diseases. Recent reports in humans and animal models have demonstrated the beneficial therapeutic effects of infections by parasitic worms (helminths) in some inflammatory disorders, such as inflammatory bowel disease (IBD) and coeliac disease (CeD). Interestingly, these studies have described how helminths may alter the intestinal microbiota, potentially representing a mechanism by which they regulate inflammation.

Hookworm recombinant protein promotes regulatory T cell responses that suppress experimental asthma.

In the developed world, declining prevalence of some parasitic infections correlates with increased incidence of allergic and autoimmune disorders. Moreover, experimental human infection with some parasitic worms confers protection against inflammatory diseases in phase 2 clinical trials. Parasitic worms manipulate the immune system by secreting immunoregulatory molecules that offer promise as a novel therapeutic modality for inflammatory diseases.

A Case of Ancylostoma ceylanicum Infection Occurring in an Australian Soldier Returned from Solomon Islands.

A 26-year-old male member of the Australian Defense Force presented with a history of central abdominal pain of 4 weeks duration and peripheral eosinophilia consistent with eosinophilic enteritis. Acute hookworm disease was diagnosed as the cause. Adult worms recovered from feces after therapy with albendazole were morphologically consistent with Ancylostoma ceylanicum.

The Intestinal Microbiota Contributes to the Ability of Helminths to Modulate Allergic Inflammation.

Intestinal helminths are potent regulators of their host's immune system and can ameliorate inflammatory diseases such as allergic asthma. In the present study we have assessed whether this anti-inflammatory activity was purely intrinsic to helminths, or whether it also involved crosstalk with the local microbiota. We report that chronic infection with the murine helminth Heligmosomoides polygyrus bakeri (Hpb) altered the intestinal habitat, allowing increased short chain fatty acid (SCFA) production.

Experimental hookworm infection and escalating gluten challenges are associated with increased microbial richness in celiac subjects.

The intestinal microbiota plays a critical role in the development of the immune system. Recent investigations have highlighted the potential of helminth therapy for treating a range of inflammatory disorders, including celiac disease (CeD); however, the mechanisms by which helminths modulate the immune response of the human host and ameliorate CeD pathology are unknown. In this study, we investigated the potential role of alterations in the human gut microbiota in helminth-mediated suppression of an inflammatory disease.

Suppression of inflammation by helminths: a role for the gut microbiota?

Multiple recent investigations have highlighted the promise of helminth-based therapies for the treatment of inflammatory disorders of the intestinal tract of humans, including inflammatory bowel disease and coeliac disease. However, the mechanisms by which helminths regulate immune responses, leading to the amelioration of symptoms of chronic inflammation are unknown. Given the pivotal roles of the intestinal microbiota in the pathogenesis of these disorders, it has been hypothesized that helminth-induced modifications of the gut commensal flora may be responsible for the therapeutic properties of gastrointestinal parasites.

Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease.

Background: Celiac disease (CeD) is a common gluten-sensitive autoimmune enteropathy. A gluten-free diet is an effective treatment, but compliance is demanding; hence, new treatment strategies for CeD are required.

Objective: Parasitic helminths hold promise for treating inflammatory disorders, so we examined the influence of experimental hookworm infection on the predicted outcomes of escalating gluten challenges in CeD subjects.

Impact of experimental hookworm infection on the human gut microbiota.

The interactions between gastrointestinal parasitic helminths and commensal bacteria are likely to play a pivotal role in the establishment of host-parasite cross-talk, ultimately shaping the development of the intestinal immune system. However, little information is available on the impact of infections by gastrointestinal helminths on the bacterial communities inhabiting the human gut. We used 16S rRNA gene amplification and pyrosequencing to characterize, for the first time to our knowledge, the differences in composition and relative abundance of fecal microbial communities in human subjects prior to and following experimental infection with the blood-feeding intestinal hookworm, Necator americanus.

Changed gluten immunity in celiac disease by Necator americanus provides new insights into autoimmunity.

We recently completed clinical trials in people with diet-treated celiac disease who were purposefully infected with the ubiquitous human hookworm, Necator americanus. Hookworm infection elicited not only parasite-specific immunity but also modified the host's immune response to gluten. After infection, mucosal IL-1β and IL-22 responses were enhanced, but IFNγ and IL-17A levels and circulating regulatory T cells following gluten challenge were suppressed, and the adaptive response to gluten acquired a helper T cell type-2 profile.