Cryptosporidium is an apicomplexan parasite that causes gastrointestinal disease in a wide variety of hosts and is associated with waterborne outbreaks. Nonetheless, the parasite is underdiagnosed. Cryptosporidium has been proposed as an etiological cause of irritable bowel syndrome (IBS) in several studies. However, the exact mechanism of pathogenesis is unknown, and no direct link has been discovered. This review will discuss several parasite-induced modifications, such as immunological, microbiome, and metabolite modifications, as well as their interactions. To summarize, Cryptosporidium causes low inflammation, dysbiosis, and unbalanced metabolism, which leads to a lack of homeostasis in the intestine in a comparable pattern to postinfectious IBS.

Cryptosporidium spp. is an apicomplexan protozoan parasite associated with gastroenteritis in humans. In 2018, Spain showed 1511 confirmed cases, with a growing trend since 2014. Despite this fact, Cryptosporidium spp. is not usually routinely examined when a parasitological study is ordered, although accurate diagnosis is fundamental to prevent the spread of the illness. The main objectives of the present work is to demonstrate the circulation and to study the epidemiology of cryptosporidiosis in patients who were being tested for the presence of Cryptosporidium spp. parasites in the faeces in the Metropolitan North Area of Barcelona, Maresme, and Vallés Occidental using a two-step algorithm. The stool samples were analysed using the Cryptosporidium/Giardia spp. immunochromatographic test; the positive samples were visualised under a microscope using auramine staining. The proportion of Cryptosporidium spp. cases was around 2% in the studied patients, with a pronounced seasonal incidence peak in late summer-early autumn. In our cohort, weight loss was the main symptom related to confirmed cases. The mean age of confirmed patients was 19 years old, and they were younger than the unconfirmed group. Cryptosporidium spp. is one of the parasites that currently circulate in many areas in Europe. Prevalence must be taken into account for active searching.

As a common functional gastrointestinal disorder, irritable bowel syndrome (IBS) significantly affects personal health and imposes a substantial economic burden on society, but the current understanding of its occurrence and treatment is still inadequate. Emerging evidence suggests that IBS is associated with gut microbial dysbiosis, but most studies focus on the bacteria and neglect other communities of the microbiota, including fungi, viruses, archaea, and other parasitic microorganisms. This review summarizes the latest findings that link the nonbacterial microbiota with IBS. IBS patients show less fungal and viral diversity but some alterations in mycobiome, virome, and archaeome, such as an increased abundance of Candida albicans. Moreover, fungi and methanogens can aid in diagnosis. Fungi are related to distinct IBS symptoms and induce immune responses, intestinal barrier disruption, and visceral hypersensitivity via specific receptors, cells, and metabolites. Novel therapeutic methods for IBS include fungicides, inhibitors targeting fungal pathogenic pathways, probiotic fungi, prebiotics, and fecal microbiota transplantation. Additionally, viruses, methanogens, and parasitic microorganisms are also involved in the pathophysiology and treatment. Therefore, the gut nonbacterial microbiota is involved in the pathogenesis of IBS, which provides a novel perspective on the noninvasive diagnosis and precise treatment of this disease.

As an essential part of the immune system, mast cells (MCs) play an important role in the pathogenesis of irritable bowel syndrome (IBS). Accumulating evidence has identified altered MC count and density in intestinal mucosa of patients with IBS; however, conflicting findings yield inconsistent conclusions. Currently, most studies have suggested intestinal MC infiltration in IBS patients. Considering the pivotal role of MCs in IBS, it is necessary to achieve a better understanding about the pathological changes in the intestine. The risk factors for IBS, including dietary habits, psychological factors, infection, and dysbiosis, are implicated to induce intestinal MC infiltration. Mechanistically, food may trigger immune-related allergic reactions and affect the intestinal microbiota activity. Some exogenous pathogens and altered profile of commensal bacteria promote intestinal MC recruitment through promoted release of chemokines from epithelial cells or direct activation of the immune system. In addition, psychological factors may affect the microenvironment where MCs live. MCs have been proven to interact with the enteric neurons and other immunocytes, evidenced by the close proximity of MCs to neurons and regional altered immune system components. A variety of mediators released by the enteric neurons, immunocytes, and MCs per se, such as neurotrophins, neuropeptides, cytokines, and chemokines, may have stimulant effects on MCs by modulating the survival, proliferation, and recruitment process of MCs in the intestine. In this review, the associations between IBS and intestinal MC density and the underlying mechanisms are discussed.

Cryptosporidium parvum is an important coccidian parasite that could infect the intestine, respiratory and biliary tracts of man and animals. This study aims to test the potential therapeutic and prophylactic effects of a natural herbal agent (Asafoetida) versus the nowadays drug of choice (Nitazoxanide). Fifty bred female, white Albino mice of CDI strain were divided into 5 groups; group I (GI): immunosuppressed, infected with C. parvum and treated with Asafoetida, group II (GII): immunosuppressed, prophylactically treated with Asafoetida for 7 days prior to infection, group III (GIII): immunosuppressed, infected and treated with Nitazoxanide, group IV (GIV): immunosuppressed and infected (Positive control), group V (GV): immunosuppressed and non infected (Negative control). Parasitological and histopatholgical examinations of the stool, ileocaecal and liver specimens were performed for the study groups. GI showed reduction of the mean oocyst count in stool with improvement of the pathological changes at the ileocaecal region with preservation of hepatic architecture. Results of GI were better than GII and GIV but not as good as GIII. GII showed the least improvement among the test groups. GIII showed the best response between the test groups. GIV show no statistical significant difference between the mean oocyst count in the mice stool at the time of infection and 7 days after infection. It was therefore concluded that Asafoetida is a promising natural therapeutic and prophylactic agent against cryptosporidiosis while, Nitazoxanide is the best chemotherapeutic agent against cryptosporidiosis.

The existence of postinfection irritable bowel syndrome (PI-IBS) has been substantiated by epidemiology studies conducted in diverse geographic and clinical settings. However, the available evidence has not been well summarized, and there is little guidance for diagnosis and treatment of PI-IBS. The ROME Foundation has produced a working team report to summarize the available evidence on the pathophysiology of PI-IBS and provide guidance for diagnosis and treatment, based on findings reported in the literature and clinical experience.

The working team conducted an evidence-based review of publication databases for articles describing the clinical features (diagnosis), pathophysiology (intestinal sensorimotor function, microbiota, immune dysregulation, barrier dysfunction, enteroendocrine pathways, and genetics), and animal models of PI-IBS. We used a Delphi-based consensus system to create guidelines for management of PI-IBS and a developed treatment algorithm based on published findings and experiences of team members.

PI-IBS develops in about 10% of patients with infectious enteritis. Risk factors include female sex, younger age, psychological distress during or before acute gastroenteritis, and severity of the acute episode. The pathogenesis of PI-PBS appears to involve changes in the intestinal microbiome as well as epithelial, serotonergic, and immune system factors. However, these mechanisms are incompletely understood. There are no evidence-based, effective pharmacologic strategies for treatment of PI-IBS. We provide a consensus-based treatment algorithm, based on clinical presentation and potential disease mechanisms.

Based on a systematic review of the literature and team experience, we summarize the clinical features, pathophysiology (from animal models and human studies), and progression of PI-IBS. Based on these findings, we present an algorithm for diagnosis and treatment of PI-IBS based on team consensus. We also propose areas for future investigation.

Somatostatins are proteins that are involved in gastrointestinal function. However, little is known with regard to somatostatin receptor subtype (SSTR) expression changes that occur in the jejunum during low-grade inflammation and during subsequent octreotide treatment. The aim of the present study was to investigate the expression of SSTRs in the jejunums of Cryptosporidium parvum (C. parvum)-infected rats by immunohistochemisty, reverse transcription (RT) PCR and quantitative real-time RT-PCR assays. Five-day-old suckling Sprague-Dawley rats (n = 15 for each group) were orally gavaged with 105 Nouzilly isolate (NoI) oocysts. Rats then received 50 μg/kg/day of octreotide by intraperitoneal injection from day 10 to day 17 post-infection. Animals were sacrificed on days 7 and 14 post-infection for immunohistochemical analysis and on days 14, 35 and 50 for mRNA expression analysis of SSTR subtypes. Histological analysis of jejunum tissues demonstrated infection of C. parvum along the villus brush border on day 7 post-infection and infection clearance by day 14 post-infection. Real-time PCR analysis indicated that in the inflamed jejunum, a significant increase in SSTR1 and SSTR2 expression was observed on day 14 post-infection. Octreotide therapy down-regulated the expression of SSTR2 on day 37 post-infection but significantly increased expression of SSTR1, SSTR2 and SSTR3 on day 50 post-infection. The results indicate that specific SSTRs may regulate the inflammatory pathway in the rat intestinal inflammation model.

Visceral hypersensitivity induced by stress is quite common in irritable bowel syndrome (IBS) patients. Probiotics play an important role in reducing visceral hypersensitivity in IBS patients. However, the mechanism has not been clearly elucidated. In this study, we investigated the role of nod-like receptor pyrin domain-containing protein 6 (NLRP6) in Clostridium butyricum-regulated IBS induced by stress. Our results showed that NLRP6 was down-regulated in IBS group colon tissues. In addition, IL-18, IL-1β, myeloperoxidase (MPO), d-lactic acid (D-LA), and CD172a were up-regulated in the IBS group of colonic mucous. IL-18 and IL-1β were also increased after the NLRP6 gene was silenced. Pathological score suggested low inflammation of colonic mucous rather than terminal ileum. Water-avoidance stress (WAS) showed visceral hypersensitivity to colonic distension. However, treatment with Clostridium butyricum reversed these results, exerting a beneficial effect. In conclusion, Clostridium butyricum may exert a beneficial action on visceral hypersensitivity of IBS by inhibiting low grade inflammation of colonic mucous through its action on NLRP6.

To investigate the putative role of protozoan parasites in the development of irritable bowel syndrome (IBS).

The study included 109 IBS consecutive adult patients fulfilling the Rome III criteria and 100 healthy control subjects. All study subjects filled a structured questionnaire, which covered demographic information and clinical data. Fresh stool samples were collected from patients and control subjects and processed within less than 2 h of collection. Iodine wet mounts and Trichrome stained smears prepared from fresh stool and sediment concentrate were microscopically examined for parasites. Blastocystis DNA was detected by polymerase chain reaction, and Cryptosporidium antigens were detected by ELISA.

A total of 109 IBS patients (31 males, 78 females) with a mean age ± SD of 27.25 ± 11.58 years (range: 16 -60 years) were enrolled in the study. The main IBS subtype based on the symptoms of these patients was constipation-predominant (88.7% of patients). A hundred healthy subjects (30 males, 70 females) with a mean ± SD age of 25.0 ± 9.13 years (range 18-66 years) were recruited as controls. In the IBS patients, Blastocystis DNA was detected in 25.7%, Cryptosporidium oocysts were observed in 9.2%, and Giardia cysts were observed in 11%. In the control subjects, Blastocystis, Cryptosporidium and Giardia were detected in 9%, 0%, and 1%, respectively. The difference in the presence of Blastocystis (P = 0.0034), Cryptosporidium (P = 0.0003), and Giardia (P = 0.0029) between IBS patients and controls was statistically significant by all methods used in this study.

Prevalence of Blastocystis, Cryptosporidium and Giardia is higher in IBS patients than in controls. These parasites are likely to have a role in the pathogenesis of IBS.

We describe a longitudinal study carried out in an adult outbreak-associated cohort to investigate health effects, including post-infectious irritable bowel syndrome, occurring after resolution of acute Cryptosporidium parvum infection. New symptoms self-reported up to 12 months included: weight loss (31 %), abdominal pain (38 %), diarrhoea (33 %), eye pain (9 %), joint pain (33 %), fatigue (22 %) and symptoms consistent with irritable bowel syndrome (IBS) (28 %). Two people were medically diagnosed with IBS. This study describes for the first time sequelae reported by patients up to 12 months after infection with C. parvum, which appear to be similar to those described with C. hominis.

Cryptosporidium has emerged as a significant cause of diarrhoeal disease worldwide, with severe health consequences for very young, malnourished children living in endemic areas and for individuals with highly impaired T-cell functions. In Europe, as elsewhere, the burden of disease has been difficult to measure as a result of the lack of appropriate, standardized surveillance and monitoring systems. The recent occurrence of large water- and foodborne outbreaks in several EU countries, as well as the results of many surveys of human and animal cryptosporidiosis, indicate that this parasite is widespread. Specific subtypes of the zoonotic Cryptosporidium parvum and the anthroponotic C. hominis are responsible for the majority of human cases in Europe. No treatment is currently available to clear the infection, but recent progress in genetic engineering of the parasite, coupled with advances in genomics, have opened important avenues for future research. Here we explore the possible reasons for underascertainment of cryptosporidiosis and the importance of accurate diagnosis in clinical management, the epidemiology of human cryptosporidiosis and key messages from recent outbreaks to highlight important interventions and emerging public health issues.

Irritable bowel syndrome (IBS) is the most frequent functional gastrointestinal disorder. It is characterized by abdominal hypersensitivity, leading to discomfort and pain, as well as altered bowel habits. While it is common for IBS to develop following the resolution of infectious gastroenteritis [then termed postinfectious IBS (PI-IBS)], the mechanisms remain incompletely understood. Giardia duodenalis is a cosmopolitan water-borne enteropathogen that causes intestinal malabsorption, diarrhea, and postinfectious complications. Cause-and-effect studies using a human enteropathogen to help investigate the mechanisms of PI-IBS are sorely lacking. In an attempt to establish causality between giardiasis and postinfectious visceral hypersensitivity, this study describes a new model of PI-IBS in neonatal rats infected with G. duodenalis At 50 days postinfection with G. duodenalis (assemblage A or B), long after the parasite was cleared, rats developed visceral hypersensitivity to luminal balloon distension in the jejunum and rectum, activation of the nociceptive signaling pathway (increased c-fos expression), histological modifications (villus atrophy and crypt hyperplasia), and proliferation of mucosal intraepithelial lymphocytes and mast cells in the jejunum, but not in the rectum. G. duodenalis infection also disrupted the intestinal barrier, in vivo and in vitro, which in turn promoted the translocation of commensal bacteria. Giardia-induced bacterial paracellular translocation in vitro correlated with degradation of the tight junction proteins occludin and claudin-4. The extensive observations associated with gut hypersensitivity described here demonstrate that, indeed, in this new model of postgiardiasis IBS, alterations to the gut mucosa and c-fos are consistent with those associated with PI-IBS and, hence, offer avenues for new mechanistic research in the field.

The protozoan Cryptosporidium is a major public and animal health concern. Young children, immunocompromised people, and pre-weaning animals are especially vulnerable, but treatment options are limited and there is no vaccine. A laboratory diagnosis is required to confirm cases of cryptosporidiosis, and species and genotype determination is essential in distinguishing human from non-human sources, understanding transmission, and strengthening the epidemiological evidence for causative links in outbreaks. However, testing is not consistent, as demonstrated by investigation of a significant increase in cases in some European countries during 2012. Many methods employed are laborious and time-consuming; recent advances, translated into diagnostic assays, can improve testing and facilitate typing to support clinical and environmental investigations.

Mast cells might play an important role as the major effector cells in the immune response against Cryptosporidium parvum. C. parvum is a protozoan parasite that causes cryptosporidiosis in animals and humans worldwide. To investigate the interaction between C. parvum and mast cells during infection, nine 3-day-old male calves were orally challenged with 10(6) oocysts of C. parvum per calf. The distribution of mast cells in the mucosa of the small intestine was analyzed by toluidine blue staining. The concentrations of histamine and the cytokines interferon-γ, interleukin-4, interleukin-2, and interleukin-12 were measured in the serum, and the histamine levels were also determined from the intestinal contents. The following clinical signs were monitored: nausea, watery diarrhea, dehydration, and weight loss. Oocysts were shed in the feces during the infection period. C. parvum infection induced an increase in mast cell numbers in the mucosa of the small intestine in distinct temporal and spatial patterns. Infection with C. parvum can induce mastocytosis in the entire small intestinal mucosa in immune-competent calves, and the presence of the parasites influences the distribution profile of the mast cells.

Similar to other bacterial or protozoan infections, human cryptosporidiosis may trigger postinfectious irritable bowel syndrome (IBS)-like symptoms, a condition in which enhanced visceral perception of pain during intestinal distension plays a pivotal role. In an immunocompetent suckling rat model which mimicks features of postinfectious IBS, Cryptosporidium parvum infection induces long-lasting jejunal hypersensitivity to distension in association with intestinal activated mast cell accumulation. The aim of the present study was to explore in this model whether octreotide, a somatostatin agonist analog, could prevent the development of jejunal hypersensitivity and intestinal mast cell/nerve fiber accumulation.

Five-day-old Sprague-Dawley rats were infected with C. parvum and treated 10 days later with octreotide (50 g kg(-1) day(-1), i.p.) for 7 days.

Compared with untreated infected rats, octreotide treatment of infected rats resulted in increased weight gain [day 23 postinfection (PI)], decreased food intake (day 16 PI), and a reduction in jejunal villus alterations (day 14 PI), CD3(+) IEL (day 37 PI) and mast cell (days 37 and 50 PI) accumulations, nerve fiber densities (day 50 PI), and hypersensitivity to distension (day 120 PI). In uninfected rats, the effects of octreotide treatment were limited to higher weight gain (days 16 and 23 PI) and decreased food intake (day 23 PI) compared with uninfected-untreated rats.

Data confirms the relevance of the present rat model to postinfectious IBS studies and prompt further investigation of somatostatin-dependent regulatory interactions in cryptosporidiosis.

Post-infectious irritable bowel syndrome (PI-IBS) is a subset of IBS which occurs after an episode of acute gastrointestinal infections. The mechanisms of PI-IBS are not fully understood. Currently, numerous animal models have been used in the study of PI-IBS. This article reviews the strengths and weaknesses of these models.

All relevant articles were identified by searching in Ovid SP from 1962, the year the term PI-IBS was coined, up to December 31, 2009. The types of model were categorized as either post-infectious or post-inflammatory, and the characteristics of each kind of model were listed.

Based on our literature search, 268 articles were identified. Of those articles, 50 were included in this review. The existing PI-IBS models include infection with bacteria (e.g., Campylobacter jejuni, Salmonella enterica, and Campylobacter rodentium), and infection with parasites (e.g., Trichinella spiralis, Nippostrongylus brasiliensis, and Cryptosporidium parvum). The post-inflammatory IBS models are commonly induced with chemical agents, such as acetic acid, deoxycholic acid, dextran sulfate sodium, mustard oil, zymosan, and trinitrobenzene sulfonic acid (TNBS). TNBS is the most commonly used agent for post-inflammatory IBS models, but the experimental protocol varies. These models have one or more aspects similar to IBS patients.

Different methods have been used for the development of post-infectious or post-inflammatory IBS models. Each model has its weaknesses and strengths. More studies are needed to establish post-infection IBS models using more common pathogens. A standard protocol in developing TNBS-induced post-inflammatory IBS model is needed.