The therapeutic goal in ulcerative colitis is mucosal healing, which requires improved non-invasive biomarkers to evaluate disease activity. Gelsolin is associated with several autoimmune diseases, and here, we aimed to analyze its usefulness as a serological biomarker for clinical and endoscopic activities in ulcerative colitis. Patients with ulcerative colitis (n = 138) who had undergone blood tests and colonoscopy were included. Serum gelsolin was measured using enzyme-linked immunosorbent assay, and correlation between the gelsolin level and clinical and endoscopic activities was examined. The serum gelsolin level in patients with ulcerative colitis was significantly lower than that in healthy subjects, and it decreased in proportion to increasing Mayo score and Mayo endoscopic subscore. The area under the curve for correlation between clinical and endoscopic remission and serum gelsolin level was higher than that for C-reactive protein. Furthermore, in C-reactive protein-negative patients, the serum gelsolin level was lower in the active phase than in remission. Our findings indicate that the serum gelsolin level correlates with clinical and endoscopic activities in ulcerative colitis, has a higher sensitivity and specificity than C-reactive protein, and can detect mucosal healing, suggesting that gelsolin can be used as a biomarker for ulcerative colitis.

Background: Ulcerative colitis involves an excessive immune response to intestinal bacteria. Whether administering prebiotic 1-kestose is effective for active ulcerative colitis remains controversial.Aims: This randomised, double-blind, placebo-controlled pilot trial investigated the efficacy of 1-kestose against active ulcerative colitis.Methods: Forty patients with mild to moderate active ulcerative colitis were randomly treated with 1-kestose (N = 20) or placebo (maltose, N = 20) orally for 8 weeks in addition to the standard treatment. The Lichtiger clinical activity index and Ulcerative Colitis Endoscopic Index of Severity were determined. Faecal samples were analysed to evaluate the gut microbiome and metabolites. Results:The clinical activity index at week 8 was significantly lower in the 1-kestose group than in the placebo group (3.8 ± 2.7 vs. 5.6 ± 2.1, p = 0.026). Clinical remission and response rates were higher in the 1-kestose group than in the placebo group (remission: 55% vs. 20%, p = 0.048; response: 60% vs. 25%, p = 0.054). The Ulcerative Colitis Endoscopic Index of Severity at week 8 was not significantly different (2.8 ± 1.6 vs. 3.5 ± 1.6, p = 0.145). Faecal analysis showed significantly reduced alpha-diversity in the 1-kestose group, with a decreased relative abundance of several bacteria, including Ruminococcus gnavus group. The short-chain fatty acid levels were not significantly different between the groups. The incidence of adverse events was comparable between the groups.Discussion: Oral 1-kestose is well tolerated and provides clinical improvement for patients with mild to moderate ulcerative colitis through modulation of the gut microbiome.

We thank Dr. Chen and Dr. Chen for their comments regarding our study on the efficacy and safety of 1-kestose for patients with mild to moderate ulcerative colitis (UC). 1,2 Regarding the authors' first point, the maltose used as placebo in this study is approximately 20 kcal/5 g. As the authors point out, we agree that long-term administration is undesirable because it leads to obesity and glucose intolerance, but this study was conducted for a short period of 2 months, and hence, we believe that the effect would be limited.Furthermore, in this study, each product was packaged individually as a single dose in an opaque package and the entire product kit was also packaged in such a way that the contents are not revealed.Participants were allocated only one product, either 1-kestose or placebo (maltose). Importantly, they could not compare the weights of the two products. Therefore, participants could not identify the allocated product. Although there are product storage and contamination issues, it would be a useful and interesting idea to use liquid percentage concentrations to adjust doses.Second, as mentioned in the limitation section, the patients in this study had mild to moderate UC and were not administered uniform/similar treatment. Therefore, it is not possible to have a control group that receives similar treatment strategies. Hence, placebo (maltose) is used. Further, we believe that the use of maltose as a placebo is appropriate because polysaccharides such as maltodextrin have been used as placebos in previous clinical trials on prebiotics for UC. 3,4 Furthermore, as noted in the paper, both groups were instructed to continue all therapeutic agents used prior to the study.Third, as the authors point out, 1-kestose is present in foods such as onions and asparagus, but the amount is so small that it is unlikely to affect the results. 5 In addition, the participants were instructed to eat their usual diet during the study, so it is unlikely that 1-kestose in food influenced the results.Fourth, the papers the authors pointed to regarding age-dependent changes in the effect of 1-kestose are for children under 5 years of age. 6 We were unable to identify any reports of differences in the effect of 1-kestose in adults (e.g. younger vs. older). Furthermore, we divided the 1-kestose group into two groups, those younger than 40 years (N = 10) and those older than 40 years (N = 10), and found no significant differences in baseline gut microbiota, disease activity or treatment efficacy (data not shown). However, further validation is needed to determine in which cases 1-kestose is effective.