Revealation Of The Relationship Between The Intestinal Bacterial Community And Two Kinds Of Gut Diseases

Human gut microbiota plays an essential role in the physiology, nutrition and immunity of human hosts and it may be closely related with the pathogenesis of many intestinal diseases. This study will explore the intestinal bacterial composition alteration in two intestinal diseases, rotavirus-infected diarrhea and ulcerative colitis.Rotavirus-infected diarrhea is a leading cause of infantile gastroenteritis worldwide and it can cause approximately 20% of diarrhea-associated deaths in children under 5 years old and surviving children may become failure to thrive. Although probiotics have been widely used to alleviate the problem, the bacterial composition alteration due to the infection remains obscure. In this study, we focused on the changes of a major member in the intestine-Bacteroides spp. in response to rotavirus infection. 9 rotavirus-infected (Group R) and 12 healthy children (Group H) were studied in this work. Real-time PCR was used to evaluate the population levels of Bacteroides spp. in healthy children and rotavirus-infected children and one saturated clone library was also constructed for each individual to retrieve the structural features of gut microbiota in these two groups. The results showed that the 16S rDNA copies of Bacteroides spp. decreased in rotavirus-infected children by 2 orders of magnitudes. 665 clones in Group H and 284 clones in Group R were sequenced and 34 OTUs were obtained according to 98% sequence homology. Partial least squares discriminant analysis of the clone library profiling data revealed significant structural shifts of gut microbiota. Bacteroides vulgatus, Bacteroides stercoris and Bacteroides fragilis were identified as key populations in response to the infection with Marten's uncerntainty test. This study not only revealed the Bacteroides spp. structural alteration under the rotavirus-infected diarrhea but also provides a new strategy, which can be applied to retrieve structural patterns from large-scale phylogenetic sequencing data and search specific populations as biomarkers for indicating the responses of gut microbiota to infectious/noninfectious disturbances or nutritional/ drug interventions.The other disease studied in this work is ulcerative colitis (UC), which is one type of inflammatory bowel diseases (IBD). The etiology of IBD remains unknown, but work with animal models have shown that resident intestinal bacteria are closely related to the pathogenesis of this disease. To understand the role of the mucosa-associated microbiota in pathogenicity of ulcerative colitis (UC), paired biopsies were obtained during colonoscopy from the ulcerated and nonulcerated gut mucosa of 24 patients with UC. The dominant bacteria and four important groups lactic acid bacteria (LAB), Clostridium leptum subgroup, Bacteroides spp. and Bifidobacteria were also profiled by denaturing gradient gel electrophoresis (DGGE) analysis. The results indicated that lactic acid bacteria (LAB) and Clostridium leptum subgroup were significantly different between ulcerated and nonulcerated regions. It was also noted that the location of UC in the gut has different influence on the bacterial community alteration. The presence of the band nearest to B. longum, decreased in frequency UC patients compared with the healthy controls. Localized dysbiosis of the mucosa-associated intestinal microflora, especially for lactic acid bacteria (LAB) and Clostridium leptum subgroup may be closely related to UC.This work indicates that specific structural patterns may be associated with infectious or non-infectious gut diseases. It may be possible to retrieve these patterns as molecular ecological markers to evaluate health status of the gut and provide new insights to gut disease with unknown etiology.