Published papers

Background: Despite the proven efficacy of immune checkpoint inhibitors (ICIs) against various types of malignancies, they have been found to induce immune-related adverse events, such as enterocolitis; however, the clinical features of ICI-induced enterocolitis remain to be sufficiently elucidated, which is significant, considering the importance of early detection in the appropriate management and treatment of ICI-induced enterocolitis. Therefore, the current study aimed to determine the utility of capsule endoscopy as a screening tool for ICI-induced enterocolitis. Methods: This single-center, prospective, observational study was conducted on patients with malignancy who received any ICI between April 2016 and July 2020 at Keio University Hospital. Next, second-generation capsule endoscopy (CCE-2) was performed on day 60 after ICI initiation to explore the entire gastrointestinal tract. Results: Among the 30 patients enrolled herein, 23 underwent CCE-2. Accordingly, a total of 23 findings were observed in 14 (60.8%) patients at any portion of the gastrointestinal tract (7 patients in the colon, 4 patients in the small intestine, 2 patients in both the colon and the small intestine, and 1 patient in the stomach). After capsule endoscopy, 2 patients (8.7%) developed ICI-induced enterocolitis: both had significantly higher Capsule Scoring of Ulcerative Colitis than those who had not developed ICI-induced enterocolitis (p = 0.0455). No adverse events related to CCE-2 were observed. Conclusions: CCE-2 might be a safe and useful entire intestinal tract screening method for the early detection of ICI-induced enterocolitis in patients with malignancies.

Background: Vonoprazan, a potassium-competitive acid blocker (VPZ), significantly reduces postoperative bleeding after gastric ESD; however, there is no consensus on the appropriate treatment duration. We conducted a randomized controlled study to demonstrate that the 3-week administration of VPZ is not inferior to the 8-week administration for ulcer healing. Methods: This is a prospective, open-label multicenter randomized controlled trial. Patients aged 20–85 years undergoing gastric ESD were included in this study. The key exclusion criteria were patients with bleeding tendencies and those taking NSAIDs, steroids, PPIs, or VPZ medications. Eligible patients were randomly assigned to the VPZ 3w or 8w treatment group. The primary endpoint was the proportion of patients with complete closure of the post-ESD wound at 24 weeks after ESD. The key secondary endpoints included the proportion of patients with complete closure of the post-ESD wound at 8 weeks and the proportion of bleeding or perforation more than 3 weeks after ESD. Results: From May 2018 to October 2020, 234 patients were included. The proportion of patients with complete ulcer closure was significantly lower in the 3w group than in the 8w group (70.8% vs. 90.6%) at 8 weeks post-treatment. The complete closure rates at 24 weeks in the 3w and 8w groups were 99.1% and 99.2%, respectively. The absolute difference in the closure rate at 24 weeks was − 0.059% [95% confidence interval (CI) -3.4% to 3.2], and the lower limit of the 95% CI exceeded -10%, the preset threshold. None of the patients developed delayed bleeding 3 weeks after ESD. Conclusion: This multicenter randomized study demonstrated that 3 weeks of treatment with VPZ is sufficient for ulcer healing. Trial registry number. UMIN000031564.

Immune checkpoint inhibitors (ICPI) have been reported to be effective in various carcinomas. They excessively activate the immune system, resulting in frequent immune-related adverse events (irAEs). Colitis induced by ICPI is one of the most common and is known as immune-mediated colitis (IMC). Although IMC and inflammatory bowel disease (IBD) are similar in many respects, there are very few reports of IMC in patients with preexisting IBD such as ulcerative colitis (UC) and Crohn's disease (CD). Whether preexisting IBD is concerned with the development of the colitis is not well known. Here, we reported the case who developed severe ulcerative colitis which started from IMC. It is an important case to follow the time course of the colitis developed. Our conclusion indicated that frequent colonoscopy was important for the management of IMC in a patient who has suffered chronic inflammatory disease, such as UC.

Background/Aims: Poorly differentiated adenocarcinoma, signet-ring cell carcinoma, and mucinous adenocarcinoma (por/sig/muc), which are considered to be histologic subtypes with a poor prognosis, occur more frequently with colitis-associated cancer than with sporadic tumors. However, their invasiveness and manifestations are unclear. This study aimed to determine the prevalence of the por/sig/muc component in ulcerative colitis-associated neoplasms (UCANs) and its association with invasiveness and to clarify its clinicohistologic and endoscopic features. Methods: This retrospective observational study included patients diagnosed with ulcerative colitis-associated high-grade dysplasia or adenocarcinoma from 1997 to 2022 who were divided according to the presence or absence of a por/sig/muc component. Results: Thirty-five patients had UCAN with a por/sig/muc component and 66 had UCAN without this component. The 5-year survival rate was significantly lower in the por/sig/muc group than in the tub group (67% vs. 96%, P=0.001), which was attributed to disease above stage III and depth to below the subserosa. Biopsy-based diagnosis before resection detected a por/sig/muc component in only 40% of lesions (14/35). Lesions with a por/sig/muc component were prevalent even in the early stages: stage 0 (4/36, 11%), I (8/20, 40%), II (7/12, 58%), III (10/14, 71%), and IV (6/8, 75%). Conclusions: This is the first investigation that shows UCANs with a por/sig/muc component tended to be deeply invasive and were often not recognized preoperatively. Endoscopists should be aware that UCAN often has a por/sig/muc component that is not always recognized on biopsy, and the optimal treatment strategy needs to be carefully considered.

Background: Endoscopic resection (ER) is increasingly utilized for ulcerative colitis-associated neoplasias (UCANs); however, these lesions demonstrate higher rates of local residuals and recurrences compared with sporadic neoplasias. This may be partly explained by challenges in accurately delineating lesion borders preoperatively, though their clinicopathologic features remain incompletely understood. Objectives: This study aimed to characterize the endoscopic and histologic features associated with local residuals and recurrences following ER for UCAN. Design: A retrospective observational study. Methods: Patients diagnosed with UCAN exhibiting a p53 mutation pattern between 2005 and 2024 and suspected of having local residual or recurrent lesions after ER were included. Endoscopic and histologic features were evaluated. Results: Of 122 UCAN patients, 13 (6 underwent initial ER at our institution before 2018, and 7 underwent initial ER elsewhere) were identified with suspected local residuals or recurrences. Prior to initial ER, p53 immunostaining was not performed in eight cases (five without biopsy and three with biopsy specimens not stained), and only two patients underwent biopsy of the surrounding tissue. Ten tumors had positive or potentially positive horizontal margins (HMs) that were not identified endoscopically at the time of ER. All local recurrences were associated with suspected positive HMs, with a median time to recurrence of 16.5 (8.5–23.8) months. At recurrence, 50% of the lesions appeared flat, while the remaining 50% were superficial elevated lesions with adjacent flat dysplasia. Conclusion: Inadequate preoperative assessment of the horizontal extent of UCANs may contribute to residual or recurrent disease after ER. Comprehensive evaluation—including p53 immunostaining and careful inspection for surrounding flat dysplasia—may improve curative outcomes in UCAN management.

Background and aims: Endoscopic remission is known to be defined as a Mayo endoscopic subscore (MES) of ≤1 in patients with ulcerative colitis (UC). However, some individuals experience relapse even after showing endoscopic remission under white-light imaging (WLI), and no tool exists that can detect these individuals. The aim of this study was to clarify the usefulness of texture and color enhancement imaging (TXI) in the assessment of inflammation in patients with UC. Methods: This was a prospective, single-arm, observational study conducted at a university hospital. From January 2021 to December 2021, 146 UC patients with endoscopic remission were enrolled. Images were evaluated by WLI, TXI, and pathologic evaluation, followed by prognostic studies. The primary endpoint of the study was the cumulative relapse of UC in each TXI score. The secondary endpoints were the association between TXI and pathologic scores, predictors of relapse, and interobserver agreement between the MES and TXI scores. Results: Patients with TXI score 2 had significantly lower UC relapse-free rates than did those with TXI scores 0-1 (log-rank test, P < .01). When pathologic remission was defined as Matts grade ≤2, the rate of pathologic remission decreased significantly with higher TXI scores (P = .01). In multivariate analysis, TXI score 2 was the only risk factor for UC relapse (P < .01; hazard ratio, 4.16; 95% confidence interval, 1.72-10.04). Interobserver agreement on the TXI score was good (κ = 0.597-0.823). Conclusion: TXI can be used to identify populations with poor prognosis in MES 1, for whom treatment intensification has been controversial.

A 77-year-old female who had an acute severe abdominal pain was taken to the emergency room in the previous hospital. CT scans showed jejunum and ileum wall thickening and fatty deposits around the small intestinal tract, and gastrointestinal perforation could not be ruled out. By using single anal and oral balloon endoscopy, we observed mild edema with petechial erythema, shallow erosions with edematous mucosa and ulcers with surrounded disrupted villous structures at the jejunum and ileum. Histological analysis revealed atypical lymphocytes infiltrating the small intestinal mucosa demonstrating intraepithelial lymphocytosis. Immunohistochemical staining revealed that CD3, CD7, and CD56 staining was positive, and CD4, CD5, and CD8 staining was negative in infiltrated lymphocytes. We made the diagnosis of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) with the combination of HE staining and IHC. PET-CT showed abnormal uptake in irregular wall thickening of the small intestine, lymph nodes, ribs, spine and pelvic bone. She was treated with chemotherapy (etoposide, prednisolone, oncovin, cyclophosphamide, hydroxydaunorubicin) and is still alive 1 year after the diagnosis. We reported the various endoscopic findings in the same MEITL patient by using single balloon endoscopy. We also summarized endoscopic characteristics of MEITL patients.

Since its introduction into clinical practice in 2000, capsule endoscopy (CE) has become an important procedure for many pathologies of small bowel (SB) diseases, including inflammatory bowel disease (IBD). Currently, the most commonly used capsule procedures are small bowel capsule endoscopy (SBCE), colon CE (CCE), and the recently developed pan-enteric CE that evaluates the SB and colon in patients with Crohn's disease (CD). SBCE has a higher diagnostic performance compared to other radiological and conventional endoscopic modalities in patients with suspected CD. Additionally, CE plays an important role in monitoring the activity of CD in SB. It can also be used in evaluating response to anti-inflammatory treatment and detecting recurrence in postsurgical patients with CD who underwent bowel resection. Due to its increasing use, different scoring systems have been developed specifically for IBD. The main target with CCE is ulcerative colitis (UC). The second-generation colon capsule has shown high performance for the assessment of inflammation in patients with UC. CCE allows noninvasive evaluation of mucosal inflammation with a reduced volume of preparation for patients with UC.

Objective: This study aimed to evaluate the use of video capsule endoscopy (VCE) in patients with obscure gastrointestinal bleeding (OGIB), compare cases of overt and occult OGIB, assess the rates of balloon-assisted enteroscopy (BAE) interventions and rebleeding, and identify predictive markers of positive VCE findings. Methods: Medical records of 430 patients who underwent VCE for OGIB between 2004 and 2022 were analyzed. Occult OGIB was defined as IDA or positive fecal occult blood, whereas overt OGIB was defined as clinically imperceptible bleeding. We retrospectively analyzed demographics, VCE findings based on Saurin classification (P0, P1, and P2), outcome of BAE interventions, and rebleeding rates. Results: A total of 253 patients with overt OGIB and 177 with occult OGIB were included. P1 findings were predominant in both groups, with a similar distribution. The percentage of patients receiving conservative therapy was higher in P1 than in P2 for both overt and occult OGIB. BAE was more frequently performed in P2 than in P1 VCE (83.0% vs. 35.3% in overt OGIB, 84.4% vs. 24.4% in occult OGIB). The percentage of positive findings and intervention in total BAE performed patients were comparable in P1 and P2 of overt OGIB, whereas these percentages in P2 were more than P1 of occult OGIB. Conclusion: VCE effectively identified OGIB lesions requiring intervention, particularly occult OGIB lesions, potentially reducing unnecessary BAE. Rebleeding rates varied according to the VCE findings, emphasizing the importance of follow-up in high-risk patients.

Objectives: The risk of colitis-associated cancer increases with disease duration in ulcerative colitis (UC), yet surveillance colonoscopy protocols generally stratify risk uniformly for patients with disease lasting over 8 years. This study evaluated whether shorter surveillance intervals might enhance lesion detection rates in patients with extended disease duration. Methods: This retrospective observational study analyzed patients diagnosed with UC-associated neoplasms between 2010 and 2023. Colonoscopies before lesion detection were retrospectively reviewed, and risk stratification was applied according to four established guidelines. The recommended surveillance intervals were recalculated based on the stratified risk, and lesion detection rates were compared across increasing risk categories for specific disease duration. Results: A total of 39 patients were included, with a median disease duration of 21 years (14–27), and a median colonoscopy interval of 1.3 years (1.1–2.2). Lesion detection rates were 72%, 59%, 44%, and 56% for American Society for Gastrointestinal Endoscopy (ASGE), American Gastroenterological Association (AGA), European Crohn's and Colitis Organisation (ECCO), and British Society of Gastroenterology (BSG) guidelines, respectively. Adjusting risk stratification upward by one rank for disease durations of ≥ 15, ≥ 20, ≥ 25, and ≥ 30 years resulted in increased detection rates: 90%, 87%, 82%, and 72% for ASGE; 85%, 82%, 74%, and 64% for AGA; 82%, 74%, 62%, and 49% for ECCO; and 82%, 79%, 72%, and 62% for BSG, respectively. The longest period with a significant difference in detection rates was observed in patients with disease durations of 20–25 years. Conclusions: For patients with long-standing UC, reducing surveillance intervals may improve the detection of colitis-associated neoplasia, with a practical focus on those with 20–25 years of disease duration.

CD4+Foxp3+ regulatory T cells (Tregs) are essential for homeostasis in the colon, but the mechanism by which local environmental cues determine the localization of colonic Tregs is unclear. Here, we administer indigo naturalis (IN), a nontoxic phytochemical aryl hydrocarbon receptor (AhR) agonist used for treating patients with ulcerative colitis (UC) in Asia, and we show that IN increases Helios+ Tregs and MHC class II+ epithelial cells (ECs) in the colon. Interactions between Tregs and MHC class II+ ECs occur mainly near the crypt bottom in the steady state, whereas Tregs dramatically increase and shift toward the crypt top following IN treatment. Moreover, the number of CD25+ T cells is increased near the surface of ECs in IN-treated UC patients compared with that in patients treated with other therapies. We also highlight additional AhR-signaling mechanisms in intestinal ECs that determine the accumulation and localization of Helios+ Tregs in the colon.

Objectives: Despite recent advances in endoscopic equipment and diagnostic techniques, early detection of ulcerative colitis-associated neoplasia (UCAN) remains difficult because of the complex background of the inflamed mucosa of ulcerative colitis and the morphologic diversity of the lesions. We aimed to describe the main diagnostic patterns for UCAN in our cohort, including lateral extension surrounding flat lesions. Methods: Sixty-three lesions in 61 patients with flat-type dysplasia that were imaged with dye chromoendoscopy (DCE) were included in this analysis. These DCE images were analyzed to clarify the dye-chromoendoscopic imaging characteristics of flat dysplasia, and the lesions were broadly classified into dysplastic and nondysplastic mucosal patterns. Results: Dysplastic mucosal patterns were classified into two types: small round patterns with round to roundish structures, and mesh patterns with intricate mesh-like structures. Lesions with a nondysplastic mucosal pattern were divided into two major types: a ripple-like type and a gyrus-like type. Of note, 35 lesions (55.6%) had a small round pattern, and 51 lesions (80.9%) had some type of mesh pattern. About 70% of lesions with small round patterns and 49% of lesions with mesh patterns were diagnosed as high-grade dysplasia or carcinoma, while about 30% of lesions with small round patterns and 51% of lesions with mesh patterns were diagnosed as low-grade dysplasia. Conclusion: When a characteristic mucosal pattern, such as a small round or mesh pattern, is found by DCE, the possibility of UCAN should be considered.

Objectives: Despite recent advances in endoscopic equipment and diagnostic techniques, early detection of ulcerative colitis-associated neoplasia (UCAN) remains difficult because of the complex background of the inflamed mucosa of ulcerative colitis and the morphologic diversity of the lesions. We aimed to describe the main diagnostic patterns for UCAN in our cohort, including lateral extension surrounding flat lesions. Methods: Sixty-three lesions in 61 patients with flat-type dysplasia that were imaged with dye chromoendoscopy (DCE) were included in this analysis. These DCE images were analyzed to clarify the dye-chromoendoscopic imaging characteristics of flat dysplasia, and the lesions were broadly classified into dysplastic and nondysplastic mucosal patterns. Results: Dysplastic mucosal patterns were classified into two types: small round patterns with round to roundish structures, and mesh patterns with intricate mesh-like structures. Lesions with a nondysplastic mucosal pattern were divided into two major types: a ripple-like type and a gyrus-like type. Of note, 35 lesions (55.6%) had a small round pattern, and 51 lesions (80.9%) had some type of mesh pattern. About 70% of lesions with small round patterns and 49% of lesions with mesh patterns were diagnosed as high-grade dysplasia or carcinoma, while about 30% of lesions with small round patterns and 51% of lesions with mesh patterns were diagnosed as low-grade dysplasia. Conclusion: When a characteristic mucosal pattern, such as a small round or mesh pattern, is found by DCE, the possibility of UCAN should be considered.

Background: Ulcerative colitis (UC) is characterized by chronic intestinal epithelial damage, and previous studies have evaluated the epithelial structure of patients with active UC using electron microscopy. Aims: This study aimed to assess the intestinal epithelial structure using scanning electron microscopy (SEM) and the features of patients with UC who are in remission. Methods: In total, eight healthy controls and 20 patients with UC were enrolled, and colonic tissue samples from the cecum and rectum were collected. Then, we compared the epithelial surface structure on SEM between patients with UC who are in clinical remission and healthy controls. Results: In healthy controls, the colonic surface comprises small lobes (termed units), with one crypt located in the middle of each unit. In patients with UC, we found irregular unit and crypt mouth size, double crypt sign (> 1 crypt per unit), and lower number of small vesicles in the intestinal epithelial cells. Compared with healthy controls, patients with UC often presented with irregular unit size, double crypt sign, and irregular crypt mouth size in the rectum. The small vesicles were observed less frequently in patients with UC than in healthy controls. Conclusions: SEM revealed a unique epithelial structure in patients with UC who are in remission.

Chronic enteropathy associated with solute carrier organic anion transporter family, member 2A1 (SLCO2 A1) (CEAS) is a rare autosomal recessive hereditary disease characterized by chronic persistent anemia and hypoproteinemia. Its diagnosis typically requires a genetic analysis. The efficacy of immunohistochemical staining with SLCO2A1 polyclonal antibody as a pre-diagnostic tool for CEAS has been previously reported. We herein report a patient with CEAS in whom immunohistochemical staining confirmed SLCO2A1 protein expression. The immunopositive results may have been due to nonsense-mediated RNA decay. As immunohistochemical staining of SLCO2A1 protein may show immunopositive results, a genetic analysis should also be performed when CEAS is strongly clinically suspected.

Indigo naturalis is an effective treatment for ulcerative colitis. However, long-term use of indigo naturalis causes adverse events, such as pulmonary hypertension. The natural history of patients with ulcerative colitis who discontinued indigo naturalis after induction therapy is unknown. Moreover, the clinical features of patients who relapsed within 52 weeks after the discontinuation of indigo naturalis are unclear. This study aimed to assess the clinical outcomes of patients with ulcerative colitis after discontinuation of indigo naturalis and to identify potential markers responsible for relapse. This single-center retrospective study investigated the follow-up of 72 patients who achieved a clinical response 8 weeks after indigo naturalis treatment. We observed relapse in patients with ulcerative colitis after the discontinuation of indigo naturalis. We analyzed the factors predicting long-term outcomes after discontinuation of indigo naturalis. Relapse was observed in 24%, 57%, and 71% of patients at 8, 26, and 52 weeks, respectively. There were no predictive markers in patients who relapsed within 52 weeks after the discontinuation of indigo naturalis. The ulcerative colitis relapse rate after indigo naturalis discontinuation was high. Follow-up treatment is required after the discontinuation of indigo naturalis in patients with ulcerative colitis.

Background: In patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), antiplatelet medication usage is crucial for preventing thrombotic events. However, it requires careful monitoring, especially because of the risk of life-threatening bleeding complications. In hemorrhagic complications, assessment of patient background and risk of gastrointestinal bleeding (GIB) remain limited for GIB that develops during long-term observation after hospital discharge. This study aimed to examine the incidence of GIB and patient characteristics in CAD post-PCI. Methods: All CAD patients undergoing PCI for urgent, emergent, or elective indications were enrolled in the Keio Interhospital Cardiovascular Studies (JCD-KiCS)-PCI registry (January 2009 and December 2017) and followed up to 2 years after PCI discharge. From the JCD-KiCS PCI registry, 8864 patients (median [interquartile range [IQR]] age: non-GIB: 69.0 y [16 y], upper GIB (UGI): 72.0 y [15.5 y], lower GIB (LGI): 73.0 y [IQR: 13 y]) were categorized based on the occurrence of hospitalization-requiring GIB. Patient characteristics and detailed information regarding these GIB events, including the location (upper vs lower GI) and bleeding severity, were analyzed. Results: Overall, 36 patients experienced UGI, while 85 patients experienced LGI. The rates of dual antiplatelet therapy (DAPT) and triple therapy were significantly different among the non-GIB (n = 8734), UGI (n = 36) and LGI (n = 85) groups (DAPT [aspirin + P2Y12 (clopidogrel/prasugrel/ticlopidine)]: 64 [76.2 %] in the LGI group vs 24 [68.6 %] in the UGI group vs 7330 [84.6 %] in the non-GIB group; triple therapy [aspirin + P2Y12 (clopidogrel/prasugrel/ticlopidine)] + oral anticoagulant (OAC) (warfarin/direct oral anticoagulant [DOAC]): 17 [20.2 %] in the LGI group vs 8 [22.9 %] in the UGI group vs 836 [9.6 %] in the non-GIB group; p < 0.001). In the LGI and UGI groups, aspirin and warfarin were used in 2 (2.4 %) and 2 (5.7 %) patients, respectively, but not in combination with DOAC. The 2-year post-PCI hospitalization incidence for GIB was 1.4 % (LGI, 1.0 %; UGI, 0.4 %). The most common causes were colonic diverticular hemorrhage (43.5 %) for LGI and duodenal ulcer (21.9 %) for UGI. No significant differences were found in the cumulative 2-year post-PCI risks between the LGI and UGI groups (log-rank p = 0.97). Most GIB events were Bleeding Academic Research Consortium 2-equivalent (hemoglobin decrease <3 g/dL). Notably, the use of OACs at PCI discharge, bleeding complications within 72 h, and preprocedural anemia were significantly correlated with an increased GIB risk. Conclusions: The real-world incidence of LGI is two times higher than that of UGI in CAD patients undergoing PCI, and most events are mild. OAC use at PCI discharge is the strongest potential risk factor for GIB development.

While both the annual incidence and mortality of colorectal cancer are slowly but steadily decreasing in the United States, the incidence of such malignancy is increasing in Japan. Thus, controlling colorectal cancer in Japan is a major concern. In 2006, colon capsule endoscopy was first introduced by Eliakim et al. First-generation colon capsule endoscopy had a moderate sensitivity for detecting polyps of more than 6 mm. Thus, second-generation colon capsule endoscopy was developed to achieve higher sensitivity. Colonoscopy is the gold standard tool for colorectal cancer surveillance. With an improvement in the imaging function, the performance of second-generation colon capsule endoscopy is almost as satisfactory as that of colonoscopy. Certain situations, such as incomplete colonoscopy and contraindication for use of sedation, can benefit from colon capsule endoscopy. Colon capsule endoscopy requires a more extensive bowel preparation than colonoscopy and computed tomography colonography because it requires laxatives not only for bowel cleansing but also for promoting the excretion of the capsule. Another problem with colon capsule endoscopy includes the burden of reading and interpretation and overlook of the lesions. Currently, the development of automatic diagnosis of colon capsule endoscopy using artificial intelligence is still under progress. Although the available guidelines do not support the use of colon capsule endoscopy for inflammatory bowel disease, the possible application of colon capsule endoscopy is ulcerative colitis. This review article summarizes and focuses on the current status of colon capsule endoscopy for colorectal cancer screening and the possibility for its applicability on inflammatory bowel disease.

Background & Aims: D-amino acids, the chiral counterparts of protein L-amino acids, were primarily produced and utilized by microbes, including those in the human gut. However, little was known about how orally administered or microbe-derived D-amino acids affected the gut microbial community or gut disease progression. Methods: The ratio of D- to L-amino acids was analyzed in feces and blood from patients with ulcerative colitis (UC) and healthy controls. Also, composition of microbe was analyzed from patients with UC. Mice were treated with D-amino acid in dextran sulfate sodium colitis model and liver cholangitis model. Results: The ratio of D- to L-amino acids was lower in the feces of patients with UC than that of healthy controls. Supplementation of D-amino acids ameliorated UC-related experimental colitis and liver cholangitis by inhibiting growth of Proteobacteria. Addition of D-alanine, a major building block for bacterial cell wall formation, to culture medium inhibited expression of the ftsZ gene required for cell fission in the Proteobacteria Escherichia coli and Klebsiella pneumoniae, thereby inhibiting growth. Overexpression of ftsZ restored growth of E. coli even when D-alanine was present. We found that D-alanine not only inhibited invasion of pathological K. pneumoniae into the host via pore formation in intestinal epithelial cells but also inhibited growth of E. coli and generation of antibiotic-resistant strains. Conclusions: D-amino acids might have potential for use in novel therapeutic approaches targeting Proteobacteria-associated dysbiosis and antibiotic-resistant bacterial diseases by means of their effects on the intestinal microbiota community.