| In the past two decades,the alterations in structures and metabolic states of microbiota under disease conditions were widely studied,with technological advances and cost reductions in omics studies.And roles of the microbiota in human health and diseases have been explored in depth.Relationships between microbiota and various diseases are gradually understood with the supports of a lot of experimental evidences.The related diseases not only involve infectious diseases,but also include metabolic diseases,neuropsychiatric diseases and even tumors.Based on the relationships between microbiota and human diseases,the microbiota modulations have become a novel strategy for the medical practice and stimulate the development of the food and drug industries.Thus,basic researches about microbiota modulation are extremely important.Bacteriophages can specifically act on their host bacteria and down-regulate the abundance of those bacteria in microbiota.To identify phages are important for microbiota related diseases and better understand the role of phages in micro-ecology,type 2 diabetes(T2D)patients were selected as our study objects.A metagenomic method based on virus-like particles(VLPs)isolation was used for exploring the alteration of gut phageome in T2 D patients and the interaction of phageome and bacterial microbiota.A consortia of 8 phages was found to distinguish T2 D patients from nondiabetic controls with a good performance(AUC>0.99).Additionally,based on our data,we speculated that lipopolysaccharide(LPS)produced by the lysis of Enterobacteriaceae bacteria caused by their specific phages might play an important role in the development and progression of T2 D.In addition,in order to promote applications of microecological modulators for intervening colorectal cancer(CRC),2strains of bacteriophages targeting Fusobacterium nucleatum(F.nucleatum),which has been confirmed to be closely related to CRC by previous studies in gut microbiota,were isolated.They may act as reducing the abundance of F.nucleatum in gut.The genomic structures,biological characteristics,and safety assessments at genomic level of the 2phages were studied.In addition,prebiotics,another method to manipulate microbiota via stimulating probiotics was studied.In order to determine whether a novel prebiotic blend(PB)could modulate the microbiota and be effective in preventing the development of irritable bowel syndrome(IBS),we firstly conducted a study on Caco-2 cells,of which the results suggested a promising anti-inflammatory effect of PB in vitro.C57BL/6 mice were selected for establishing IBS mice model.The expression levels of proinflammatory factors were significantly down-regulated in intestinal tissues,while the intestinal epithelial tight junction protein was significantly up-regulated in PB treated mice.Moreover,the fecal bacterial microbiota structure in mice with PB-treated was similar to that of the health controls.The results indicated that PB was capable of modifying microbiota and ameliorating the gut inflammation.Further study indicated the anti-inflammatory effect of PB in IBS might be exerted through peroxisome proliferator-activated receptor gamma(PPAR?)pathway.In this thesis,we conducted a preliminary study on the role and possible mechanisms of different micro-ecological intervention strategies in non-infectious diseases such as T2 D,CRC,and IBS.The characteristics of different components in the gut microbiota of T2 D patients and IBS mice were analyzed,and partially revealed the relationship between the microbiota alterations and diseases.The prospect of possible micro-ecological intervention was proposed.Furthermore,phages of F.nucleatum which are closely related to colorectal cancer were isolated for potential micro-ecological applications. |
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