66 However, such apparently diverse literature can be explained, at least Etoposide in vitro 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 Selumetinib clinical trial 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 infestation67 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 MCE公司 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. Gut flora could affect the sensorimotor functions of the gut in three ways: (i) end products of bacterial fermentation and metabolism; (ii) neuroendocrine factors; and (iii) immune mediators. Bacterial chemotactic peptides, such as formyl–methionyl–leucyl–phenylalanine, stimulate the enteric nervous system and afferent nerves, while endotoxin (lipopolysaccharide) may affect gut motility.3 Short-chain fatty acids (SCFA), such as butyrate, acetate, and propionate have important roles in gut health and motility and may contribute to pathogenesis of gastrointestinal diseases.