Remission Factors for Ustekinumab Treatment of Ulcerative Colitis: A Multicenter Retrospective Study of Real-World Data in Japan.

Ustekinumab (UST) is an anti-IL-12/23p40 monoclonal antibody used to treat inflammatory bowel disease. The aim of this retrospective, multicenter study was to investigate the effectiveness of UST administration in achieving remission in patients with ulcerative colitis (UC) and to determine patient characteristics that influence its effectiveness. Of 88 UC patients who received UST from March 2020 to August 2023, 47 with traceable data and for whom 56 weeks had elapsed since the start of treatment received UST to induce remission. The remission rates at 8 weeks were 66% overall, 73.7% for Bio Naïve (never used biologics/JAK inhibitors), and 60.7% for Bio Failure (used biologics/JAK inhibitors) groups. Remission rates at 56 weeks were 70.2% overall, 73.7% for Bio Naïve, and 67.9% for Bio Failure groups. Ustekinumab showed good mid-to-long-term results in the induction of remission of UC in both Bio Naïve and Bio Failure groups. The group showing remission at 8 weeks had a significantly higher non-relapse or continuation rate (proportion of patients with no worsened symptoms necessitating surgery/drug change) at 56 weeks. Predictive factors for achieving remission after UST in UC were female gender, low body mass index, and low lymphocyte-to-monocyte ratio. Thus, UST is effective for moderate-to-severe UC.

Anti-inflammatory Effects of Bacteroidota Strains Derived From Outstanding Donors of Fecal Microbiota Transplantation for the Treatment of Ulcerative Colitis.

BACKGROUND: The proportion of certain Bacteroidota species decreased in patients with ulcerative colitis, and the recovery of Bacteroidota is associated with the efficacy of fecal microbiota transplantation therapy. We hypothesized that certain Bacteroidota may advance ulcerative colitis treatment. Accordingly, we aimed to evaluate the anti-inflammatory effects of Bacteroidota strains isolated from donors. METHODS: Donors with proven efficacy of fecal microbiota transplantation for ulcerative colitis were selected, and Bacteroidota strains were isolated from their stools. The immune function of Bacteroidota isolates was evaluated through in vitro and in vivo studies. RESULTS: Twenty-four Bacteroidota strains were isolated and identified. Using an in vitro interleukin (IL)-10 induction assay, we identified 4 Bacteroidota strains with remarkable IL-10-induction activity. Of these, an Alistipes putredinis strain exhibited anti-inflammatory effects in a mouse model of colitis induced by sodium dextran sulfate and oxazolone. However, 16S rRNA gene-based sequencing analysis of A. putredinis cultures in the in vivo study revealed unexpected Veillonella strain contamination. A second in vitro study confirmed that the coculture exhibited an even more potent IL-10-inducing activity. Furthermore, the production of A. putredinis-induced IL-10 was likely mediated via toll-like receptor 2 signaling. CONCLUSIONS: This study demonstrated that A. putredinis, a representative Bacteroidota species, exhibits anti-inflammatory effects in vivo and in vitro; however, the effects of other Bacteroidota species remain unexplored. Our fecal microbiota transplantation-based reverse translation approach using promising bacterial species may represent a breakthrough in microbiome drug development for controlling dysbiosis during ulcerative colitis.

We isolated Bacteroidota species from the feces of donors who were effectively cured of UC with fecal microbiota transplantation and proved the anti-inflammatory effects of Bacteroidota species, especially Alistipes putredinis, through cell experiments and in vivo experiments.

Free water in gray matter linked to gut microbiota changes with decreased butyrate producers in Alzheimer's disease and mild cognitive impairment.

Neuroinflammation contributes to the pathology and progression of Alzheimer's disease (AD), and it can be observed even with mild cognitive impairment (MCI), a prodromal phase of AD. Free water (FW) imaging estimates the extracellular water content and has been used to study neuroinflammation across several neurological diseases including AD. Recently, the role of gut microbiota has been implicated in the pathogenesis of AD. The relationship between FW imaging and gut microbiota was examined in patients with AD and MCI. Fifty-six participants underwent neuropsychological assessments, FW imaging, and gut microbiota analysis targeting the bacterial 16S rRNA gene. They were categorized into the cognitively normal control (NC) (n = 19), MCI (n = 19), and AD (n = 18) groups according to the neuropsychological assessments. The correlations of FW values, neuropsychological assessment scores, and the relative abundance of gut microbiota were analyzed. FW was higher in several white matter tracts and in gray matter regions, predominantly the frontal, temporal, limbic and paralimbic regions in the AD/MCI group than in the NC group. In the AD/MCI group, higher FW values in the temporal (superior temporal and temporal pole), limbic and paralimbic (insula, hippocampus and amygdala) regions were the most associated with worse neuropsychological assessment scores. In the AD/MCI group, FW values in these regions were negatively correlated with the relative abundances of butyrate-producing genera Anaerostipes, Lachnospiraceae UCG-004, and [Ruminococcus] gnavus group, which showed a significant decreasing trend in the order of the NC, MCI, and AD groups. The present study showed that increased FW in the gray matter regions related to cognitive impairment was associated with low abundances of butyrate producers in the AD/MCI group. These findings suggest an association between neuroinflammation and decreased levels of the short-chain fatty acid butyrate that is one of the major gut microbial metabolites having a potentially beneficial role in brain homeostasis.

Small Intestinal Arteriovenous Malformation Treated by Double-balloon Endoscopy: A Case Report.

A 42-year-old man was referred to our hospital because of anemia. The patient underwent gastroscopy and colonoscopy, but no bleeding site was detected. Abdominal contrast-enhanced computed tomography (CT) showed vascular dilatation along the wall of the small intestine. Small bowel capsule endoscopy and antegrade double-balloon endoscopy (DBE) were performed, and the patient was diagnosed with a small intestinal arteriovenous malformation (AVM). The AVM was clipped using DBE. After clipping, abdominal contrast-enhanced CT and small bowel angiography revealed the disappearance of the AVM. DBE may be a viable therapeutic option, helping avoid surgery and its associated risks.

High body temperature increases gut microbiota-dependent host resistance to influenza A virus and SARS-CoV-2 infection.

Fever is a common symptom of influenza and coronavirus disease 2019 (COVID-19), yet its physiological role in host resistance to viral infection remains less clear. Here, we demonstrate that exposure of mice to the high ambient temperature of 36 °C increases host resistance to viral pathogens including influenza virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). High heat-exposed mice increase basal body temperature over 38 °C to enable more bile acids production in a gut microbiota-dependent manner. The gut microbiota-derived deoxycholic acid (DCA) and its plasma membrane-bound receptor Takeda G-protein-coupled receptor 5 (TGR5) signaling increase host resistance to influenza virus infection by suppressing virus replication and neutrophil-dependent tissue damage. Furthermore, the DCA and its nuclear farnesoid X receptor (FXR) agonist protect Syrian hamsters from lethal SARS-CoV-2 infection. Moreover, we demonstrate that certain bile acids are reduced in the plasma of COVID-19 patients who develop moderate I/II disease compared with the minor severity of illness group. These findings implicate a mechanism by which virus-induced high fever increases host resistance to influenza virus and SARS-CoV-2 in a gut microbiota-dependent manner.

Enterolith Treated with a Combination of Double-Balloon Endoscopy and Cola Dissolution Therapy.

A 71-year-old woman with rheumatoid arthritis who had been taking NSAIDs for many years consulted our hospital for abdominal pain. She was diagnosed with a small bowel obstruction due to an enterolith according to an abdominal CT scan that showed dilation from the enterolith in the small intestine on the oral side. It was considered that the intestinal stone was formed due to stagnation of intestinal contents and had gradually increased in size, resulting in an intestinal obstruction. We performed antegrade double-balloon endoscopy (DBE) to observe and remove the enterolith. We used forceps and a snare to fracture the enterolith. During this attempt, we found a seed in the center of the enterolith. Since the intestinal stone was very hard, cola dissolution therapy was administered from an ileus tube for 1 week. The following week, DBE was performed again, and it was found that the stone had further softened, making attempts at fracture easier. Finally, the enterolith was almost completely fractured. Intestinal stenosis, probably due to ulcers caused by NSAIDs, was found. Small bowel obstruction with an enterolith is rare. In this case, it was considered that the seed could not pass through the stenotic region of the small intestine and the intestinal contents had gradually built up around it. It has been suggested that DBE may be a therapeutic option in cases of an enterolith. Further, cola dissolution therapy has been shown to be useful in treating an enterolith, with the possible explanation that cola undergoes an acid-base reaction with the enterolith. In summary, we report, for the first time, treatment of an enterolith with a combination of DBE and cola dissolution therapy, thereby avoiding surgery and its risks.

Differential diagnosis of ulcerative colitis with increased diarrhea; collagenous colitis or irritable bowel syndrome? A case report.

A 50-year-old man with a 20-year history of left-sided ulcerative colitis (UC) presented to our hospital with sudden onset of watery diarrhea. To this point, he had been treated with mesalazine 2.0 g/day for UC and had maintained remission. We considered that the UC had worsened. We immediately performed surveillance colonoscopy, which revealed a normal mucous membrane. The results of blood laboratory examinations were normal. Histopathology of colonic biopsies revealed new-onset collagenous colitis (CC), with a thickened subepithelial collagen band (SECB) and inactive UC. We herein report the importance of random colonic biopsies to diagnose CC even when the endoscopic appearance of the colon is normal in patients with inflammatory bowel disease with worsened diarrhea.

Hot topics on fecal microbiota transplantation for the treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic intestinal mucosal inflammatory disease with complex etiology. Traditional anti-inflammatory treatment regimens have yielded unsatisfactory results. As research continues to deepen, it has been found that the gut microbiota of patients with IBD is generally altered. The presence of microorganisms in the human gastrointestinal tract is inextricably linked to the regulation of health and disease. Disruption of the microbiotic balance of microbiota in the gastrointestinal tract is called dysbiosis, which leads to disease. Therefore, in recent years, the exploration of therapeutic methods to restore the homeostasis of the gut microbiota has attracted attention. Moreover, the use of the well-established fecal microbiota transplantation (FMT) regimen for the treatment of Clostridioides difficile infection has attracted the interest of IBD researchers. Therefore, there are an increasing number of clinical studies regarding FMT for IBD treatment. However, a series of questions regarding FMT in the treatment of IBD warrants further investigation and discussion. By reviewing published studies, this review explored hot topics such as the efficacy, safety, and administration protocol flow of FMT in the treatment of IBD. Different administration protocols have generally shown reassuring results with significant efficacy and safety. However, the FMT treatment regimen needs to be further optimized. We believe that in the future, individual customized or standard FMT implementation will further enhance the relevance of FMT in the treatment of IBD.

Early Clinical Remission Is a Predictor of Long-Term Remission with the Use of Vedolizumab for Ulcerative Colitis.

Vedolizumab (VDZ) is an α4ß7 integrin-antibody used to manage refractory ulcerative colitis (UC). This retrospective multicenter study aimed to identify predictors of efficacy or the time points when evaluation of VDZ therapy for UC would be most useful. We compiled data on 87 patients with moderate to severe active UC that was treated with VDZ. Overall clinical remission (CR) rates at 6 weeks and 52 weeks after VDZ administration were 44.4% (bio-naïve 44.2%, bio-failure 44.8%) and 52.8% (bio-naïve 53.5%, bio-failure 51.7%) respectively. Also, 83.3% (bio-naïve 81.3%, bio-failure 85.7%) of patients achieved mucosal healing at week 52. Among patients with a CR at week 52, 73.3% had a CR at week 6. In contrast, of patients who discontinued VDZ, 82.4% had not reached a CR at week 6. Our study demonstrated that VDZ was effective in a large percentage of UC patients, with a high mucosal healing rate even after prior biological exposures. This suggests that VDZ can be a treatment option even in bio-failure cases. Additionally, it was considered that early CR can predict long-term remission and that week 6 can be a helpful evaluation point for treatment decisions when using VDZ for UC.

A Randomized Placebo-Controlled Trial of Combination Therapy With Post-triple-antibiotic-therapy Fecal Microbiota Transplantation and Alginate for Ulcerative Colitis: Protocol.

Background: Fecal microbiota transplantation (FMT) has been widely performed for ulcerative colitis (UC) treatment at the clinical trial stage. Previous reports have used multiple FMT methods to enhance the colonization of healthy donor microbiota in the recipient's intestines. FMT following triple antibiotic therapy with amoxicillin, fosfomycin, and metronidazole (A-FMT) is not only effective but also requires only one FMT, which improves dysbiosis caused by reduced Bacteroidetes diversity in patients with UC. Alginate and its derivatives have the potential to induce the growth of intestinal bacteria including Bacteroides members and produce short-chain fatty acids (SCFAs), which are beneficial in regulating overactive autoimmunity. Our trial aims to investigate whether post-intervention with alginate, which can improve the intestinal environment, will enhance the therapeutic effect of A-FMT in UC and increase the long-term remission rate. Methods and Analysis: This trial is a double-blinded, randomized, placebo-controlled, parallel assignment trial. Patients with UC and fecal donation candidates will undergo strict screening before being involved in the trial. Eligible patients are randomly divided into two groups: one group will drink one bottle of alginate twice a day for 8 consecutive weeks after A-FMT, while the other group will take a placebo instead of the alginate drink. The primary endpoints are the changes in the Total Mayo Score at 8 weeks after study initiation and A-FMT from baseline. The secondary endpoint is the comparison of clinical features, microbiota, and metabolomic analysis before and after 8 weeks of study food intake. Changes at 6, 12, 18, and 24 months after A-FMT will be assessed. Finally, a subpopulation analysis of the relationship between patients and donors is an exploratory endpoint. Discussion: The FMT post-treatment used in this study is an oral alginate drink that is easily accepted by patients. If the regimen achieves the desired results, it can further improve the A-FMT regimen and provide evidence for clinical practice guidelines for UC. Clinical Trial Registration: https://jrct.niph.go.jp/latest-detail/jRCTs031200103, identifier: jRCTs031200103.

Efficacy of cytapheresis for induction therapy and extra-intestinal skin manifestations of ulcerative colitis.

INTRODUCTION: In recent years, the prevalence of inflammatory bowel diseases has been increasing in Japan due to the westernization of lifestyles. Many patients have been reported to have extra-intestinal manifestations (EIMs) at least once. Skin lesions occur with a high degree of frequency among EIMs, with erythema nodosum (EN) and pyoderma gangrenosum (PG) the main complications. Cytapheresis is again attracting attention as a treatment with few side effects. METHODS: We investigated the therapeutic effect of cytapheresis on ulcerative colitis (UC) and cutaneous EIMs. Between 2008 and 2021, 240 patients with active UC had induction therapy by cytapheresis at our hospital. RESULTS: Remission and response rates were 50.0% and 67.5%, respectively. Apheresis was performed on seven patients with PG and five patients with EN with a good response. Serious adverse events were not observed. CONCLUSION: This retrospective assessment of efficacy showed that EN and PG responded favorably to cytapheresis.

Donor Screening Revisions of Fecal Microbiota Transplantation in Patients with Ulcerative Colitis.

Fecal microbiota transplantation (FMT) has been recognized as a promising treatment for dysbiosis-related diseases. Since 2014, FMT has been utilized to treat ulcerative colitis (UC) in our clinical studies and has shown efficacy and safety. As donor screening (DS) is the primary step to ensure the safety of FMT, we report our experience with DS and present the screening results to improve the prospective DS criteria and provide references for future studies. The donor candidates were screened according to the DS criteria. The first DS criteria were proposed in June 2014 and revised substantially in May 2018. We further sorted the screening results and costs of laboratory tests. From June 2014 to April 2018, the DS eligibility rate was 50%. The total laboratory testing cost for each candidate was JPY 17,580/USD 160.21. From May 2018 to September 2021, the DS eligibility rate was 25.6%. The total laboratory testing cost for each candidate was JPY 40,740/USD 371.36. The reduction in donor eligibility rates due to more stringent criteria should be considered for cost and safety. Studies must consider the latest updates and make timely modifications in the DS criteria to ensure patient safety.

Nicotine Oral Administration Attenuates DSS-Induced Colitis Through Upregulation of Indole in the Distal Colon and Rectum in Mice.

Nicotine affects the gastrointestinal environment and modulates ulcerative colitis (UC). However, the associations among nicotine, gut metabolites, and UC are still largely unknown. We investigated whether orally administered nicotine affected gut metabolites and dextran sodium sulfate (DSS)-induced colitis. C57BL/6 male mice were orally administered nicotine solution in drinking water prior to inducing DSS-induced colitis. Short-chain fatty acids (SCFAs) and indole in gut contents and fecal samples were measured by GC-MS and hydroxylamine-based indole assays, respectively. Oral administration of nicotine increased indole concentration in feces, but, in contrast, SCFA values did not differ with nicotine administration. Indole levels were increased in the distal colon and rectum but not in the cecum and proximal colon. DSS-induced colitis was less severe clinically and histological changes were minimal in the rectum of orally nicotine-administered mice compared to mice drinking only water. 16S rRNA microbiome on the feces revealed an increasing in Clostridium and Porphyromonas in nicotine-administered mice. In conclusion, nicotine administration was associated with increased indole levels in the distal colon and rectum and attenuated DSS-induced colitis. Oral administration of nicotine may play a potential role in indole upregulation and prevention of UC.

A Comparative Study of Early Mucosal Healing Following Hot Polypectomy and Cold Polypectomy.

BACKGROUND Cold polypectomy (CP) and hot polypectomy (HP) are both accepted methods for polypectomy. In recent years, the use of CP has increased for reasons of safety. However, there have been few investigations of conditions at follow-up early after resection. This prospective study from a single center aimed to compare colonic mucosal healing at 1 week following HP vs CP of benign colonic polyps <10 mm in diameter. MATERIAL AND METHODS Six patients with a total of 52 lesions under 10 mm in size were randomized to either the HP group (n=25) or CP group (n=27) using information in opaque envelopes. One week after endoscopic treatment, the site of treatment was evaluated using colonoscopy. We assessed the mean tumor size, ulcer diameter, exposed blood vessels, residual lesion, and complications. RESULTS Mean tumor size did not differ between the 2 groups (CP vs HP: 5.41 mm vs 5.68 mm). The CP group had a smaller ulcer base diameter (2.70 mm vs 4.84 mm; P<0.05) and fewer exposed blood vessels than the HP group (3.7% vs 36.0%; P<0.05). One residual lesion was found in the CP group. No patients experienced delayed perforation or post-polypectomy bleeding. CONCLUSIONS Our study findings showed that at 1-week follow-up, cold polypectomy resulted in improved colonic mucosal healing, with a smaller ulcer diameter and fewer blood vessels, when compared with hot polypectomy.

Long-term outcomes of antibiotic combination therapy for ulcerative colitis.

AIMS: An antibiotic combination of amoxicillin, tetracycline and metronidazole (ATM) is effective for ulcerative colitis (UC), but this regimen is discontinued in some cases due to adverse events. This study aimed to assess a revised combination, namely, amoxicillin, fosfomycin and metronidazole (AFM), in UC patients with the goal of reducing side effects while maintaining therapeutic efficacy. METHODS: A prospective open-label trial was undertaken in 104 adult UC patients. A combination of oral amoxicillin (1500 mg), fosfomycin (3000 mg) and metronidazole (750 mg) was administered to patients daily for 2-4 weeks in addition to their conventional medication. Clinical assessment was performed using the Lichtiger index before treatment and at 0, 3, 6, 9 and 12 months and 2 and 3 years. Endoscopic evaluation was performed using the Mayo score before treatment and at 3 and 12 months. RESULTS: The compliance rate was 99.2%. Response and remission rates were 80.8% and 63.5% at completion, 73.1% and 64.4% at 3 months, and 39.4% for both at 12 months, respectively. Of the 41 patients who were in remission at 12 months, 63.4% maintained that status until the 2-year follow-up. Similarly, 69.2% of those in remission at 2 years remained relapse free at the 3-year follow-up. Side effects were observed in 44.2% of the participants. Fever occurred in one patient (1.0%), which was lower than the rate observed with ATM therapy. CONCLUSION: These results indicate that AFM therapy induces remission and is appropriate for long-term maintenance of UC while producing fewer and milder adverse events than ATM therapy. CLINICAL TRIALS: This study was registered in the University Hospital Medical Information Network (No. R000046546).

Bacteroidetes Species Are Correlated with Disease Activity in Ulcerative Colitis.

Fecal microbiota transplantation following triple-antibiotic therapy (amoxicillin/fosfomycin/metronidazole) improves dysbiosis caused by reduced Bacteroidetes diversity in patients with ulcerative colitis (UC). We investigated the correlation between Bacteroidetes species abundance and UC activity. Fecal samples from 34 healthy controls and 52 patients with active UC (Lichtiger's clinical activity index ≥5 or Mayo endoscopic subscore ≥1) were subjected to next-generation sequencing with HSP60 as a target in bacterial metagenome analysis. A multiplex gene expression assay using colonoscopy-harvested mucosal tissues determined the involvement of Bacteroidetes species in the mucosal immune response. In patients with UC, six Bacteroides species exhibited significantly lower relative abundance, and twelve Bacteroidetes species were found significantly correlated with at least one metric of disease activity. The abundance of five Bacteroidetes species (Alistipes putredinis, Bacteroides stercoris, Bacteroides uniformis, Bacteroides rodentium, and Parabacteroides merdae) was correlated with three metrics, and their cumulative relative abundance was strongly correlated with the sum of Mayo endoscopic subscore (R = -0.71, p = 2 × 10-9). Five genes (TARP, C10ORF54, ITGAE, TNFSF9, and LCN2) associated with UC pathogenesis were expressed by the 12 key species. The loss of key species may exacerbate UC activity, serving as potential biomarkers.

Pyoderma gangrenosum in an ulcerative colitis patient during treatment with vedolizumab responded favorably to adsorptive granulocyte and monocyte apheresis.

Pyoderma gangrenosum (PG) is an extra-intestinal skin lesion in inflammatory bowel disease (IBD) as is erythema nodosum. Vedolizumab (VED) is a monoclonal antibody that targets α4ß7 integrin and has an intestinal selective mechanism. Despite good therapeutic effects on colitis, the effect on extra-intestinal manifestations (EIMs) remains unclear. Here we report a case of ulcerative colitis complicated by PG during treatment with VED, which was successfully treated with prednisolone in combination with adsorptive granulocyte and monocyte apheresis (GMA). The patient was a 50-year-old woman with a past medical history of extensive ulcerative colitis managed by golimumab (GLM). She developed flare symptoms due to loss of response to GLM, and treatment was switched to VED. Her gastrointestinal symptoms were improved with VED treatment with less frequent bowel movements. However, infiltrative erythema with pain appeared on the right lower leg and right knee, and expanded and gradually ulcerated. Her skin lesions were treated with corticosteroid, but showed poor improvement. Therefore, granulocyte and monocyte apheresis (GMA) treatment was administered in combination with prednisolone. After 3 months, the ulcer gradually improved, and at the time of this writing, the eruptions were nearly replaced by epithelial tissue. This case study showed that patients with UC and EIMS may respond well to combination therapy of VED and GMA. GMA has a very favorable safety profile. On the other hand, the causal connection between VED and PG is still unclear. We believe that a combination therapy involving VED and GMA in IBD patients with EIMs warrants consideration.

Single-cell atlas of colonic CD8+ T cells in ulcerative colitis.

Colonic antigen-experienced lymphocytes such as tissue-resident memory CD8+ T cells can respond rapidly to repeated antigen exposure. However, their cellular phenotypes and the mechanisms by which they drive immune regulation and inflammation remain unclear. Here we compiled an unbiased atlas of human colonic CD8+ T cells in health and ulcerative colitis (UC) using single-cell transcriptomics with T-cell receptor repertoire analysis and mass cytometry. We reveal extensive heterogeneity in CD8+ T-cell composition, including expanded effector and post-effector terminally differentiated CD8+ T cells. While UC-associated CD8+ effector T cells can trigger tissue destruction and produce tumor necrosis factor (TNF)-α, post-effector cells acquire innate signatures to adopt regulatory functions that may mitigate excessive inflammation. Thus, we identify colonic CD8+ T-cell phenotypes in health and UC, define their clonal relationships and characterize terminally differentiated dysfunctional UC CD8+ T cells expressing IL-26, which attenuate acute colitis in a humanized IL-26 transgenic mouse model.

Matching between Donors and Ulcerative Colitis Patients Is Important for Long-Term Maintenance after Fecal Microbiota Transplantation.

We previously demonstrated that fresh fecal microbiota transplantation (FMT) following triple antibiotic therapy (amoxicillin, fosfomycin, metronidazole (AFM); A-FMT) resulted in effective colonization of Bacteroidetes species, leading to short-term clinical response in ulcerative colitis (UC). Its long-term efficacy and criteria for donor selection are unknown. Here, we analyzed the long-term efficacy of A-FMT compared to AFM monotherapy (mono-AFM). AFM was administered to patients with mild to severe UC for 2 weeks until 2 days before fresh FMT. Clinical response and efficacy maintenance were defined by the decrease and no exacerbation in clinical activity index. The population for intention-to-treat analysis comprised 92 patients (A-FMT, n = 55; mono-AFM, n = 37). Clinical response was observed at 4 weeks post-treatment (A-FMT, 56.3%; mono-AFM, 48.6%). Maintenance rate of responders at 24 months post-treatment was significantly higher with A-FMT than mono-AFM (p = 0.034). Significant differences in maintenance rate according to the age difference between donors and patients were observed. Additionally, sibling FMT had a significantly higher maintenance rate than parent-child FMT. Microbial analysis of patients who achieved long-term maintenance showed that some exhibited similarity to their donors, particularly Bacteroidetes species. Thus, A-FMT exhibited long-term efficacy. Therefore, matching between donors and UC patients may be helpful in effectively planning the FMT regimen.

Effectiveness and Nephrotoxicity of Long-Term Tacrolimus Administration in Patients with Ulcerative Colitis.

BACKGROUND: Tacrolimus (TAC) is used for the management of ulcerative colitis (UC). However, there are few reports on the effectiveness of its long-term administration. TAC is also known to cause renal toxicity. The aim of this study was to evaluate long-term effectiveness and monitor changes in renal function during prolonged TAC use in patients with UC. METHODS: Medical records of 50 UC patients treated with TAC were retrospectively reviewed. Clinical outcomes were assessed at 6, 12, 24, and 36 months after initiating TAC. We also monitored chronological changes in renal function. RESULTS: Thirty-nine patients were treated with TAC for more than 3 months. Relapse-free survival among these patients at 6, 12, 24, and 36 months was 82%, 69%, 41%, and 23%, respectively. On the other hand, renal function was reduced in 35.9% of patients. We found that irreversible renal dysfunction was more likely to occur in cases in which the estimated glomerular-filtration rate (eGFR) was reduced by more than 30%. CONCLUSION: This study demonstrated the potential use of TAC as an effective option in the long-term medical management of UC, although it tended to increase the risk of nephrotoxicity. There is a need for the careful monitoring of renal function during TAC administration.