Review ArticleIrritable bowel syndrome: A review on the role of intestinal protozoa and the importance of their detection and diagnosis
Introduction
Irritable bowel syndrome (IBS) is defined as a functional group of bowel disorders in which abdominal pain is associated with defecation or alterations in bowel habit in the absence of an organic cause (Brandt et al., 2002). It is one of the most commonly diagnosed gastrointestinal illnesses with prevalence rates of 10ā15% in North America and Europe (Brandt et al., 2002, Mertz, 2003 ) leading to an estimated cost to the United States of 1.7 billion dollars in 2000 (Mertz, 2003). Similar rates have been documented in developing countries; although it is difficult to know how aggressively alternative diagnoses were excluded in these populations (Olubuyide et al., 1995, Curioso et al., 2002, Lule and Amayo, 2002, Gwee, 2005, Kang, 2005, OKeke et al., 2005). Irritable bowel syndrome affects all ages and all sexes with a 2:1 female predominance.
The pathophysiology of IBS remains elusive and no mechanism is unique to, or characterises, IBS. There are probably several interconnected factors which occur to varying degrees in patients that account for the clinical symptoms of IBS. These include altered gut reactivity (colonic and/or small bowel motility) in response to luminal or psychological stimuli, visceral afferent hypersensitivity, and a hypersensitive gut with enhanced visceral perception and pain (Thompson et al., 2000, Mertz, 2003). It is unclear whether this hypersensitivity is mediated via the local or central nervous system or a dysregulation of the braināgut axis. In addition, hereditary, environmental and dietary factors probably play a role (Levy et al., 2001, Brandt et al., 2002).
Persistent low-grade inflammation may play a role in IBS. It is estimated that 7ā31% of patients with infectious gastroenteritis go on to develop IBS (post-infectious IBS) (McKendrick and Read, 1994, Neal et al., 1997, Rodriguez and Ruigomez, 1999). This translates into a 14-fold increase in the overall risk of developing IBS following acute diarrhoea compared with the general population. Risk factors include longer duration of symptoms, young age and being female. The immune activation is characterised by increased intra-epithelial and lamina propria lymphocytes. These changes have been documented to persist for more than a year following the resolution of the infectious agent (McKendrick and Read, 1994, Neal et al., 1997, Rodriguez and Ruigomez, 1999). Inflammation may also occur in deeper layers of the gut. In a small IBS cohort, full-thickness biopsies revealed normal mucosa but intra- and peri-ganglionic lymphocytic infiltration at the region of the myenteric plexus (Tornblom et al., 2002). Furthermore, a correlation was revealed with the numbers of mast cells in close proximity to enteric nerves and the intensity of symptoms (Barbara et al., 2004). Most patients recover. However, in a subset of patients, persistent immune activation results in ongoing symptoms. Possible mechanisms include a genetic predisposition, continuous antigenic exposure (bacterial, parasitic or dietary) or molecular mimicry.
As there are no biological markers for IBS, diagnosis is based on a cluster of clinical symptoms (Rome II criteria; Saito et al., 2000) which include abdominal pain or discomfort with associated changes in bowel frequency and/or stool form. Symptoms may be relieved by defecation. A central feature that supports IBS is the presence of continuous or recurrent symptoms for a minimum of 3 months. Passage of mucous and bloating or sensation of abdominal distension may also occur.
There are no firm recommendations about the extent and type of testing required to exclude other organic pathology. Investigation of stool for ova, cyst and parasites is generally recommended when diarrhoea is the major manifestation of IBS. The intestinal protozoa associated with IBS-like symptoms are shown in Table 1. The role that protozoan parasites may play in this complex disease has not been fully investigated.
Section snippets
Blastocystis hominis and IBS
Blastocystis hominis is an enteric unicellular protozoan parasite that inhabits the human intestinal tract and is the most frequently reported protozoan in human faecal samples (Stenzel and Boreham, 1996). The taxonomy of B. hominis remains controversial. Although criteria by which to define the species have not been agreed upon, extensive genetic diversity was documented using numerous molecular techniques. At least 10 B. hominis subspecies (genotypes) have being identified. (Clark, 1997, Abe,
Dientamoeba fragilis and IBS
Dientamoeba fragilis is a trichomonad parasite and humans are probably the definitive host. However, there are no recent studies on the organismās host distribution and there have been few reports on D. fragilis in species other than humans. Non-human primates including macaques (Hegner and Chu, 1930, Knowles and Das Gupta, 1936) and baboons (Myers and Kuntz, 1968) were reported as having D. fragilis trophozoites in their stools and it was also reported in a sheep (Noble and Noble, 1952). Given
Entamoeba histolytica and IBS
Entamoeba histolytica is a non-flagellated amoeboid protozoan parasite. The genus Entamoeba comprises six species (E. histolytica, Entamoeba dispar, Entamoeba moshkovskii, Entamoeba poleki, Entamoeba coli and Entamoeba hartmanni), that colonise the intestinal lumen. Humans are the primary reservoir (Stauffer et al., 2006). All these species are considered commensal organisms and cause no intestinal disease with the exception of E. histolytica. Faecal carriage of E. dispar is far more common
Giardia intestinalis and IBS
Giardia intestinalis is a common and ubiquitous flagellated protozoan parasite, with a worldwide distribution. Giardia species are parasites of mammals and other animals, including reptiles and birds (Ali and Hill, 2003, Hamnes et al., 2006, Castro-Hermida et al., 2006). Humans become infected by ingestion of cysts, which develop into trophozoites after excystation. Infections occur in both developed and developing regions of the world (Savioli et al., 2006).
After acquisition, approximately 50%
Other enteric protozoa causing chronic infections
Balantidium coli is the only pathogenic ciliate to infect humans. The distribution is limited to warm tropical climates and infections are closely associated with pigs. Human infections are rare in temperate climates and in Western industrialised counties. Clinical presentations include a spectrum of disease from asymptomatic carriage to severe dysentery. Symptoms include nausea, vomiting and diarrhoea or dysentery (Garcia, 2001). The diarrhoea may persist for weeks to months with dysenteric
Importance of diagnostic tests
As discussed above, intestinal protozoa must be included in the differential diagnosis of IBS because they cause symptoms resembling IBS (Benetton et al., 2005, Stark et al., 2005b, Savioli et al., 2006) or they may be innocent bystanders, as occurs with asymptomatic carriage or infections by non-pathogenic protozoa. They may cause significant flares of IBS with acquisition. Furthermore, they may lead to IBS, secondary to ongoing low-grade inflammation. Regardless of the mechanism or
Conclusion
Irritable bowel syndrome is a complicated, multifaceted heterogeneous disorder, as opposed to a single entity disease. As the exact pathogenesis of IBS is under investigation, we can only postulate as to what, if any, roles protozoan parasites play in this condition. However, it is essential that all patients with IBS undergo routine parasitological investigations to rule out protozoan parasites as the causative agents of the clinical signs. Blastocystis hominis was reported as a possible
References (99)
- et al.
Progress in research on Entamoeba histolytica pathogenesis
Curr. Opin. Microbiol.
(2006) Molecular and phylogenic analysis of Blastocystis isolates from various hosts
Vet. Parasitol.
(2004)- et al.
Does non-dysenteric intestinal amoebiasis exist?
Lancet
(1997) - et al.
Risk factors for infection by the Entamoeba histolytica/E. dispar complex: an epidemiological study conducted in outpatient clinics in the city of Manaus, Amazon Region, Brazil
Trans. R. Soc. Trop. Med. Hyg.
(2005) - et al.
Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome
Gastroenterology
(2004) - et al.
Comparison of fluorescence, antigen and PCR assays to detect Cryptosporidium parvum in fecal specimens
Diagn. Microbiol. Infect. Dis.
(2002) Extensive genetic diversity in Blastocystis hominis
Mol. Biochem. Parasitol.
(1997)- et al.
Giardia lamblia infections become clinically evident by eliciting symptoms of irritable bowel syndrome
J. Infect.
(2002) - et al.
Dientamoeba fragilis, a neglected cause of diarrhoea, successfully treated with secnidazole
Clin. Microbiol. Infect.
(2003) - et al.
Family outbreak of Blastocystis hominis associated gastroenteritis
Lancet
(1989)
Prevalence of Cryptosporidium and Giardia in free-ranging wild cervids in Norway
Vet. Parasitol.
Irritable bowel syndrome in twins: heredity and social learning both contribute to etiology
Gastroenterology
Irritable bowel syndrome-post salmonella infection
J. Infect.
Entamoeba histolytica cyst passers: clinical features and outcome in untreated subjects
Lancet
Effect of nitazoxanide in persistent diarrhoea and enteritis associated with Blastocystis hominis
Clin. Gastroenterol. Hepatol.
A comparison of the Rome and Manning criteria for case identification in epidemiological investigations of irritable bowel syndrome
Am. J. Gastroenterol.
Giardia and Cryptosporidium join the neglected diseases initiative
Trends Parasitol.
Diagnosis by faecal culture of Dientamoeba fragilis infections in Australian patients with diarrhoea
Trans. R. Soc. Trop. Med. Hyg.
Detection of Dientamoeba fragilis in fresh stool specimens using PCR
Int. J. Parasitol.
Blastocystis in humans and animals: new insights using modern technologies
Vet. Parasitol.
Full-thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome
Gastroenterology
Clinical and microbiological features of dientamoebiasis suspected of suffering from a parasitic gastrointestinal illness: a comparison of Dientamoeba fragilis and Giardia lamblia infections
Int. J. Infect. Dis.
Blastocystis hominis infection and intestinal injury
Am. J. Med. Sci.
Giardia intestinalis
Curr. Opin. Infect. Dis.
Invasive Blastocystis hominis infection in a child
Arch. Paediatr. Adolesc. Med.
Blastocystis hominis ā a potential intestinal pathogen
West J. Med.
Systematic review on the management of irritable bowel syndrome in North America
Am. J. Gastroenterol.
Eradication of Dientamoeba fragilis can resolve IBS-like symptoms
J. Gastroenterol. Hepatol.
Enterobius vermicularis as a probable vector of Dientamoeba fragilis
Am. J. Trop. Med. Hyg.
Pathology of Dientamoeba fragilis infections in the appendix
Am. J. Trop. Med. Hyg.
Intestinal parasites: a study of human appendices
Fiola. Parasitol. (Praha)
Prevalence and intensity of infection of Cryptosporidium spp. and Giardia duodenalis in dairy cattle in Galicia (NM Spain)
J. Vet. Med. Infect. Dis. Vet. Public Health
The irritable colon syndrome; a study of the clinical features, predisposing causes and prognosis in 130 cases
Q. J. Med.
Clinical characteristics and endoscopic findings associated with Blastocystis hominis in healthy adults
Am. J. Trop. Med. Hyg.
Methods for cultivation of luminal parasitic protists of clinical importance
Clin. Microbiol. Rev.
Dientamoeba fragilis is more prevalent than Giardia duodenalis in children and adults attending a day care centre in Central Italy
Parasite
Dientamoeba fragilis masquerading as allergic colitis
J. Peadiatr. Gastroenterol. Nut.
Prevalence and relation of dyspepsia to irritable bowel syndrome in a native community of the Peruvian jungle
Rev. Gastroenterol. Peru
Blastocystis hominis: an unusual cause of diarrhoea
Br. J. Clin. Pract.
A redescription of Entamoeba histolytica Shaudinn, 1903 (amended Walker, 1911) separating it from Entamoeba dispar Brumpt, 1952
J. Eukaryot. Microbiol.
Researches on the intestinal protozoa of monkeys and man. X. The life history of Dientamoeba fragilis: observations, experiments and speculations
Parasitology
Epidemiology and pathogenicity of Blastocystis hominis
J. Clin. Microbiol.
A foodborne outbreak of Cyclospora cayetanesis at a wedding: clinical features and risk factors for illness
Arch. Intern. Med.
Blastocystis hominis enteritis
Paediatr. Infect. Dis.
Diagnostic Medical Parasitology
The association of Blastocystis hominis and Endolimax nana with diarrheal stools in Zambian school-age children
Parasitol. Res.
Giardia lamblia infection in patients with irritable bowel syndrome and dyspepsia: a prospective study
World J. Gastroenterol.
Irritable bowel syndrome in developing counties ā a disorder of civilization or colonization?
Neurogastroenterol. Motil.
Dientamoeba fragilis, a cause of illness: report of a case
Am. J. Trop. Med.
Cited by (144)
Molecular detection and subtype distribution of Blastocystis in farmed pigs in southern China
2021, Microbial PathogenesisAre intestinal parasites associated with obesity in Mexican children and adolescents?
2019, Parasitology InternationalBlastocystis subtypes and their association with Irritable Bowel Syndrome
2018, Medical HypothesesCitation Excerpt :Manuscripts considered referential on the subject were included regardless of the date of publication. Blastocystis is often detected in the stool samples of IBS patients [35ā39] and has been related to the pathogenesis of IBS in numerous studies [1,9,26,40]. Infection could be asymptomatic or could be associated to symptoms such as diarrhea, abdominal pain, nausea, vomiting, anorexia, weight loss, lassitude, dizziness, flatulence, and bloating [2,37,41].