Introduction: Ulcerative colitis (UC) has a multifactorial pathogenesis, including genetic susceptibility, environmental triggers, gut microbiota and microbial imbalance due to its immunomodulatory function. Previous studies showed that Bifidobacterium bifidum PRL2010 cells can effectively activate signals in macrophages, modulate metabolic activities and influence immune responses in vitro and when tested in a murine colitis model. The aim of this study was to characterize the microbiome of UC patients compared to healthy controls (HS), in order to evaluate the functional role of bifidobacteria as microbial biomarkers.Figure 1Methods: A stool sample was obtained from UC patients, HS and processed for microbial DNA extraction. The microbiota taxonomic profile and the bacterial population diversity index were determined by using a metagenomic approach. Patient demographics, level of disease activity and therapy were collected and analyzed. Data extracted from stool samples of UC patients were compared with those of HS. Results: Between April 2015 and April 2016, 28 patients were enrolled: 14 UC patients (mean age 39y), and 14 HS (mean age 33y). Among UC patients, 6 had active disease (3 were under therapy with infliximab, 1 with adalimumab, 1 with azathioprine), and 8 showed disease remission (3 were under therapy with azathioprine, 1 with adalimumab; 1 with mesalamine, 3 no therapy). The fecal microbiome of UC patients, independently from the type of therapy, showed a marked reduction in bacterial population diversity index. Bifidobacteria were reduced in abundance of >30 % in UC group compared to HS group. Among UC patients, those with active disease showed a significant reduction (4 fold; P< 0.05) of the bifidobacteria compared to those in remission. Conclusion:Bifidobacterium bifidum is a reliable microbial biomarker for UC. The reduction in its overall abundance and the decreased microbial diversity index appear to be related to the presence of disease and may explain, at least in part, the role of intestinal microbiome in the pathogenesis of ulcerative colitis. Moreover, the significantly different abundance of Bifidobacterium bifidum between patients with active disease and in remission, highlights that Bifidobacterium bifidum may be considered an activity index of the disease.