Background: To clarify the effect of human umbilical cord-derived mesenchymal stem cell (hUC-MSCs) treatment on colitis and to explore the role of CD5⁺ B cells in MSC therapy. Methods: The trinitrobenzenesulfonic acid (TNBS)-induced colitis mouse model was used. HUC-MSCs were transferred peritoneally. Survival rates, colitis symptoms, and macroscopic and histologic scores were evaluated. CD4⁺ T helper (Th) cell subgroups and CD5⁺ regulatory B cell (Bregs) in lymphocytes were quantitated by flow cytometry. Cytokine levels were detected by ELISA and Bio-plex. CD5⁺ B cells were isolated for in vitro co-culture and adaptive transfer. Results: HUC-MSC treatment alleviated TNBS-induced colitis by increasing survival rates, relieving symptoms, and improving macroscopic and histologic scores. Labeled hUC-MSCs were located in the inflamed areas of colitis mice. Increases in regulatory T cells (Tregs) and CD5⁺ B cells and decreases in Th1 cells, Th17 cells, and several pro-inflammatory cytokines were observed with hUC-MSC treatment. After adaptive transfer, CD5⁺ B cells, which were located mainly in the peritoneal lavage fluid, improved TNBS-induced colitis by correcting Treg/Th1/Th17 imbalances. CD5⁺ B cells also inhibited T-cell proliferation and produced interleukin (IL)-10. Conclusions: HUC-MSCs protected against experimental colitis by boosting the numbers of CD5⁺ B cells and IL-10-producing CD5⁺ Bregs, and correcting Treg/Th17/Th1 imbalances.

Ustekinumab and vedolizumab are both effective for treating Crohn’s disease (CD). However, no head-to-head trials have been conducted thus far. We aimed to compare the effectiveness of ustekinumab and vedolizumab in CD patients either naïve or exposed to tumor necrosis factor-alpha inhibitors (TNFi). Patients treated with vedolizumab or ustekinumab for luminal CD were included from six centers in China from May 2020 to July 2023. Steroid-free remission, clinical remission, objective response, and remission at Weeks 26 and 52 were evaluated in a retrospective multicenter propensity score–weighted cohort. A total of 536 patients were included (386 ustekinumab, and 150 vedolizumab). After adjustment, ustekinumab showed higher rates of clinical remission (56.4% vs. 47.8%, P = 0.005), steroid-free remission (55.4% vs. 46.1%, P = 0.003), and objective response (67.8% vs. 42.7%, P < 0.001) than vedolizumab at Week 26. At Week 52, ustekinumab exhibited significantly higher rates of clinical remission (65.8% vs. 37.5%, P < 0.001), steroid-free remission (65.8% vs. 37.5%, P < 0.001), objective response (66.7% vs. 23.8%, P < 0.001), and objective remission (31.4% vs. 12.7%, P < 0.001). Subgroup analyses revealed that ustekinumab had higher rates of clinical remission, steroid-free remission, and objective response at Weeks 26 and 52, and objective remission at Week 52 in TNFi-exposed patients, while ustekinumab showed higher rates of objective response at Weeks 26 and 52 and clinical remission, steroid-free remission and objective remission at Week 52 in TNFi-naïve patients. Adverse event rates were similar between the groups (4.9% ustekinumab vs. 6.7% vedolizumab, P = 0.423). Ustekinumab showed superior clinical and objective outcomes compared to vedolizumab, with comparable safety outcomes. The therapeutic superiority was observed in both short-term and long-term phases in TNFi-exposed patients, and the long-term phase in TNFi-naïve patients. 10.13039/501100001809 National Natural Science Foundation of China , 10.13039/501100021171 Guangdong Basic and Applied Basic Research Foundation , Key Research Projects of the Sixth Affiliated Hospital, 10.13039/501100002402 Sun Yat-sen University , the program of Guangdong Provincial Clinical Research Center for Digestive Diseases, and National Key Clinical Discipline.

Background/Aims: Data on the natural course of Chinese patients with ulcerative colitis (UC) was lacking. This study aimed to evaluate the natural history and prognosis of patients with UC in the past 15 years in China.Methods: This cohort study included patients with UC in a tertiary hospital in southern China from 2007 to 2021 (cohort I: 2007–2011, cohort II: 2012–2016, cohort III: 2017–2021). Patients’ clinical characteristics and natural history were analyzed retrospectively.Results: Of 1,139 included patients, 683 patients presented with proctitis or left-sided colitis at diagnosis and 38.5% of them (263/683) developed proximal disease extension. Fifty-eight percent of patients experienced relapse, chronic continuous and intermittent active course. Five patients (0.4%) developed colorectal tumors/dysplasia. The overall surgery rate was 8.6%, and the rates were 14.2%, 7.8%, and 8.0% in the 3 cohorts, respectively (P=0.059). Average time from diagnosis to surgery decreased from cohorts I to III (144 months vs. 36 months, P<0.001), so did the use of glucocorticoids (58.2% vs. 43.5%, P<0.001) and immunosuppressants (14.1% vs. 13.4%, P=0.016), and days of hospitalization (13 days vs. 9 days, P<0.001). Biologics were used more frequently during the first year (0.8%, 2.1%, and 13.7% for cohorts I to III, respectively; P<0.001). The rate of mucosal healing increased over time.Conclusions: In Chinese UC patients, one-third of patients experienced proximal disease extension. The rates of malignancy and mortality were low. More biologics were used, while use of immunosuppressants and glucocorticoids were reduced over time. Early biologics use seemed to promote mucosal healing, but the rate of colectomy has not dramatically decreased.

Background and aims: The efficacy and underlying mechanisms of exclusive enteral nutrition (EEN) in adult patients with Crohn’s disease (CD) remain controversial. This study aimed to evaluate the role of EEN in adult patients with CD and to explore the mechanisms from the perspective of immunoregulation. Methods: This is a prospective, open-label pilot study. Active patients with CD were enrolled and prescribed an amino-acid-rich elemental diet for 12 weeks. Dynamic changes in immune cells, including neutrophils, monocytes, T cells and B cells, were detected by flow cytometry. Plasma cytokines were evaluated by ELISA. Results: Twenty adult patients with CD were enrolled. Among them, 1 discontinued treatment due to poor compliance, and 19 patients were included for final analysis. Clinical remission was achieved in 47.37% (9/19), 63.16% (12/19), and 73.68% (14/19) patients at weeks 4, 8, and 12, respectively. Endoscopic remission and transmural healing were achieved in 52.63% (10/19) and 15.79% (3/19) patients at week 12. Notably, there was no significant difference in clinical remission between week 4 and week 8 (p = 0.33) or week 12 (p = 0.09). Furthermore, we observed a rapid reconstitution of immunologic homeostasis as early as week 4. At week 4, both the frequency and activation of neutrophils and monocytes were decreased after EEN therapy. Significant decreases in Th17 cells and naïve B cells, increases in memory B cells, and regulatory B cells were also detected. These changes remained stable at weeks 8 and 12. Conclusions: EEN with an amino-acid-rich elemental diet orchestrated immunological balances and induces clinical remission in adult CD patients as early as week 4, suggesting a 4-week EEN therapy may be feasible and practicable in clinical practice.

Background: Crohn’s disease (CD), a type of inflammatory bowel disease, is a chronic idiopathic disorder of the gastrointestinal tract with an increasing global incidence. Exclusive enteral nutrition (EEN) is a diet therapy that is effective in the management of active CD with unknown etiology. Lipid metabolism plays an important role in CD and may be associated with EEN treatment. This study compared the plasma lipid profiles before and after EEN in adults with active CD to those of healthy controls (HCs). Methods: Eleven adult patients with active CD who received enteral nutrition formula treatment for 12 weeks were included, along with 17 HCs. The profiles of 869 plasma lipid species were measured, and inflammatory and nutrition-associated indices were evaluated in the patients. Results: Nine patients achieved clinical remission following 12 weeks of EEN treatment, and four achieved mucosal healing. Before EEN, 80 lipid species and 17 lipid classes were significantly different between patients with CD and HCs. After EEN treatment, 103 lipid species and 12 lipid classes were significantly different between patients with CD and HCs. Significant changes in 7 lipid classes and 38 lipid species were observed between the pre- vs. post-treatment CD patients. The levels of simplified glucosylceramide series, monogalactosyldiacylglycerol, phosphatidylinositol, phosphatidylserine, and phosphatidylcholine increased, while those of phosphatidylglycerol and phosphatidylinositol diphosphate decreased significantly after EEN. These lipid classes and species were associated with the inflammatory and nutritional indices. Pathway analysis suggested the metabolism of arachidonic acid, glycerophospholipids, linoleate, and phosphatidylinositol phosphate was related to the EEN mechanism. Conclusions: EEN induces alterations in multiple lipid classes and species, leading to clinical improvements. Lipid metabolism may be involved in the EEN anti-inflammatory effect.