Bugs and Irritable Bowel Syndrome: The Good, the Bad and the Ugly

Uday C Ghoshal; Hyojin Park; Kok-Ann Gwee

Disclosures

J Gastroenterol Hepatol. 2010;25(2):244-251. 

In This Article

Parasites and IBS

Studies from non-Asian countries showed that Giardia lamblia infection could lead to development of functional bowel disease, including IBS.[62] In a study from Norway, structured interview and questionnaires given 12–30 months after the onset of Giardia infection revealed that 66 of 82 (81%) patients had symptoms of IBS according to Rome II criteria.[62] Diarrhea-predominant IBS was the commonest subtype (47%).[62] A few other studies from non-Asian countries showed similar findings.[63–65] In a study from Thailand, however, the frequency of detection of parasites among 59 patients with IBS diagnosed by Rome II criteria was comparable with the frequency among the control group.[66] However, this study had a case-control design with a small sample size, which might have resulted in type II statistical error. In general, persistent infection with Giardia is expected to cause chronic diarrhea, irregular bowel movement and abdominal discomfort, which may be diagnosed as IBS by a symptom-based criterion. However, there are scanty data from Asian countries where this infection is expected to be more common. For example, a study on 78 members from 15 families from rural India revealed that all except two (97%) shed parasites in the stool as detected by microscopy on alternate days for one month, and 42 (54%) showed Giardia.[67] Hence, more studies evaluating the role of Giardia lamblia in Asia are needed.

Association of Giardia infection and IBS would be of importance even in non-Asian countries due to the high frequency of giardiasis (5.3 of 100 000) in travelers returning from endemic areas.[68] Highest frequencies have been noted among travelers returning from the Indian Subcontinent (628 of 100 000), East Africa (358 of 100 000), and West Africa (169 of 100 000).[68] In a study including 328 travelers and foreign residents in Nepal, protozoal parasites were found quite commonly (Giardia in 12%, Cryptosporidium and Entamoeba histolytica each in 5%, Blastocystis hominis in 33% and mixed infestations in 17%).[69] Since as high as 80% of patients contracting Giardia infection may develop chronicity and symptoms of IBS,[62] the role of travel-acquired infection with Giardia may be of major importance.

Initial studies suggested that E. histolytica may also play a role in IBS.[21] However, two Indian studies have contradicted this hypothesis.[61,70] In one study, there were comparable frequencies of E. histolytica among 144 patients with symptoms of IBS and 100 symptom-free controls, whether detected in stool (18% vs. 18%), serological evidence of infection (42% vs. 41%), colonoscopic (7% vs. 3%) or histological abnormalities (49% vs. 30%).[70] In another study of 154 inmates of a leprosy rehabilitation home, 22 (14%) had IBS. Amoeba was detected more frequently among subjects with IBS than those without it (50% vs. 16%). Amoebae were characterized by polyacrylamide gel electrophoresis for hexokinase isoenzyme in four patients with IBS; all of these amoebae showed a slow moving band suggesting the non-pathogenic nature of the protozoa. During one year follow-up, spontaneous disappearance of amoebic cysts in the stool was not associated with a reduction in IBS symptoms.[61] Both of these studies suggested that amoeba carriage had no relationship with IBS. The discordance between older and the more recent studies might be related to the fact that whereas older studies recruited patients with invasive amoebic dysentery, the more recent Indian studies recruited chronic carriers of amoebic cysts. Since the former patients developed colonic amoebic ulcers, they might develop protracted inflammation more commonly than the latter patients. Also, patients with invasive disease are infected with pathogenic strains of amoeba as compared with chronic carriers, who usually harbor non-pathogenic strains.

Blastocystis hominis, a common intestinal parasite, has also been studied in patients with IBS. In a study from Pakistan, Blastocystis hominis was more commonly detected among 95 patients with IBS (32% and 46% by stool microscopy and culture, respectively) than 55 controls (7% both by microscopy and culture).[71] In another study from Pakistan, serological evidence of past infection (immunoglobulin G [IgG] antibody against Blastocystis hominis), was higher in stool culture-positive as well as culture-negative IBS than controls.[72] Another finding, the significance of which is yet to be determined, was that IgG2 subclass antibodies were significantly increased in IBS patients compared with asymptomatic controls.

In a study from Turkey, among 69 patients infected with Blastocystis, diarrhea was common in men, whereas dyspepsia was common among women.[73] In a study from Thailand, however, the frequency of parasites, including Blastocystis hominis, was not different among 59 patients with IBS (diagnosed using Rome II criteria) as compared with controls.[66] However, such apparently diverse literature can be explained, at least partly, by knowledge of the biology of Blastocystis. In a study using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) of the entire small-subunit rRNA (ssrRNA) revealed significant genetic variation of Blastocystis among 30 randomly selected human isolates.[74,75] These PCR-RFLP profiles (riboprints) could be grouped into seven distinct genotypes (ribodemes).[74,75] It is important to note that while some of these genotypes are potentially pathogenic, others are not.[76] In general, most studies suggest that subtype 1 is associated with disease, while subtypes 2 and 3 may be non-pathogenic.[76] However, morphologically these genotypes look quite similar.[76] Furthermore, the density of the infective organism and presence of mixed infections with different subtypes and even with other protozoa may influence the clinical outcome.[76] It follows that the contradictory findings in different studies based on isolation of Blastocystis by stool microscopy might be related to variation in pathogenic potential of the individual protozoan parasites present.

The impact of intestinal helminthic infestation on IBS is another interesting issue that has not been addressed in the published reports. Intestinal helminthes shift the immune system towards a Th2 response, which may be associated with reduced chance of protracted GI inflammation.[77,78] Low grade inflammation has been proposed as a putative pathogenic mechanism in recent models of IBS.[79,80] Hence, a high frequency of helminthic infestation[67] may explain the low frequency of IBS in tropical countries, such as India, Bangladesh and Thailand,[33] despite a high frequency of bacterial GI infections. For example, 48 of 78 (62%) subjects from rural India had hookworm infestation.[67] Despite a high frequency of bacterial GI infection, the frequency of IBS in Indian populations is 4.2%.[59] In contrast, 2% of 533 refugees from Santa Clara County, California had hookworm infestation.[81] Despite a low frequency of bacterial gastrointestinal infection, the frequency of IBS in US populations is as high as 20%.[82] Though this might suggest that helminthes can protect against PI-IBS, studies to prove such a hypothesis are not available in published reports.

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