ABSTRACT
The symbiotic relationship between gut microbiota and humans has been forged over many millennia. This relationship has evolved to establish an intimate partnership that we are only beginning to understand. Gut microbiota were once considered pathogenic, but the concept of gut microbiota and their influence in human health is undergoing a major paradigm shift, as there is mounting evidence of their impact in the homeostasis of intestinal development, metabolic activities, and the immune system. The disruption of microbiota has been associated with many gastrointestinal and nongastrointestinal diseases, and the reconstitution of balanced microbiota has been postulated as a potential therapeutic strategy. Fecal microbiota transplantation (FMT), a unique method to reestablish a sustained balance in the disrupted microbiota of diseased intestine, has demonstrated great success in the treatment of recurrent Clostridium difficile infection and has gained increasing acceptance in clinical use. The possibility of dysfunctional micro-biota playing a causative role in other gastrointestinal and nongas-trointestinal diseases, therefore, has also been raised, and there are an increasing number of studies supporting this hypothesis. FMT is emerging as a feasible therapeutic option for several diseases; however, its efficacy remains in question, given the lack of clinical trial data. Altering microbiota with FMT holds great promise, but much research is needed to further define FMT's therapeutic role and optimize the microbiota delivery system.
ABSTRACT
BACKGROUNDS/AIMS: The maintenance of telomere with telomerase reactivation, vital for carcinogenesis, was studied in human multistep hepatocarcinogenesis for the characterization of borderline lesions. METHODS: The terminal restriction fragment length (TRFL) and telomerase activity (TA) were examined in 3 chronic hepatitis (CH), 10 cirrhosis, 7 large regenerative nodules (LRNs), 30 low grade dysplastic nodules (LGDNs), 6 high grade DNs (HGDNs), 3 DNs with hepatocellular carcinoma (HCC) foci, 11 HCCs, and 4 normal livers by Southern hybridization and TRAPeze Elisa telomerase detection. RESULTS: The TRFL and TA showed significant differences between the LGDNs and HGDNs. Most LGDNs had similar levels of TRFL and TA to those of the CH, cirrhosis and LRNs, however, 17% of LGDNs revealed shortening of telomeres up to the levels of HGDNs and 7% of LGDNs showed high levels of TA. The levels of TRFL and TA in HGDNs showed no significant differences from those of DNs with HCC foci and HCCs. CONCLUSIONS: The shortening of telomeres and reactivation of telomerase occur in the DNs during the early stages of hepatocarcinogenesis, with a significant change in the transition of LGDNs to HGDNs. The characteristics of HGDNs are considered to be closer to those of HCCs.
