scholarly journals Bacteroidetes Species Are Correlated with Disease Activity in Ulcerative Colitis

2021 ◽  
Vol 10 (8) ◽  
pp. 1749
Author(s):  
Kei Nomura ◽  
Dai Ishikawa ◽  
Koki Okahara ◽  
Shoko Ito ◽  
Keiichi Haga ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Relative Abundance ◽  
Fecal Microbiota Transplantation ◽  
Activity Index ◽  
Species Abundance ◽  
Fecal Microbiota ◽  
Mucosal Immune Response ◽  
Clinical Activity ◽  
Key Species

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.

scholarly journals An Immunologic Compatibility Testing Was Not Useful for Donor Selection in Fecal Microbiota Transplantation for Ulcerative Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Manuel Ponce-Alonso ◽  
Carlota García-Hoz ◽  
Ana Halperin ◽  
Javier Nuño ◽  
Pilar Nicolás ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fecal Microbiota Transplantation ◽  
Clinical Success ◽  
Immunological Response ◽  
Organ Donor ◽  
Fecal Microbiota ◽  
Mucosal Immune Response ◽  
Donor Selection ◽  
Selection For

Fecal microbiota transplantation (FMT) is an effective procedure against Clostridioides difficile infection (CDI), with promising but still suboptimal performance in other diseases, such as ulcerative colitis (UC). The recipient’s mucosal immune response against the donor’s microbiota could be relevant factor in the effectiveness of FMT. Our aim was to design and validate an individualized immune-based test to optimize the fecal donor selection for FMT. First, we performed an in vitro validation of the test by co-culturing lymphocytes obtained from the small intestine mucosa of organ donor cadavers (n=7) and microbe-associated molecular patterns (MAMPs) obtained from the feces of 19 healthy donors. The inflammatory response was determined by interleukin supernatant quantification using the Cytometric Bead Array kit (B&D). We then conducted a clinical pilot study with 4 patients with UC using immunocompetent cells extracted from rectal biopsies and MAMPs from 3 donor candidates. We employed the test results to guide donor selection for FMT, which was performed by colonoscopy followed by 4 booster instillations by enema in the following month. The microbiome engraftment was assessed by 16S rDNA massive sequencing in feces, and the patients were clinically followed-up for 16 weeks. The results demonstrated that IL-6, IL-8, and IL-1ß were the most variable markers, although we observed a general tolerance to the microbial insults. Clinical and colonoscopy remission of the patients with UC was not achieved after 16 weeks, although FMT provoked enrichment of the Bacteroidota phylum and Prevotella genus, with a decrease in the Actinobacteriota phylum and Agathobacter genus. The most relevant result was the lack of Akkermansia engraftment in UC. In summary, the clinical success of FMT in patients with UC appears not to be influenced by donor selection based on the explored recipient’s local immunological response to FMT, suggesting that this approach would not be valid for FMT fecal donor optimization in such patients.

Treatment and mechanism of fecal microbiota transplantation in mice with experimentally induced ulcerative colitis

2021 ◽  
pp. 153537022110060
Author(s):  
Leichang Zhang ◽  
Xiaofei Ma ◽  
Peng Liu ◽  
Wei Ge ◽  
Lixia Hu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Mouse Model ◽  
Intestinal Microbiota ◽  
Relative Abundance ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Sequencing Analysis ◽  
Aminosalicylic Acid ◽  
Control Male ◽  
Experimentally Induced

Restoring intestinal microbiota dysbiosis with fecal microbiota transplantation is considered as a promising treatment for ulcerative colitis. However, the mechanisms underlying its relieving effects remain unclear. Ulcerative colitis pathogenesis is associated with the involvement of immune cells and inflammatory cytokines. Here, we aimed to investigate the effect of fecal microbiota transplantation on T cell cytokines in a dextran sulfate sodium-induced ulcerative colitis mouse model. Five-aminosalicylic acid (5-ASA) was used as the positive control. Male C57BL/6 mice were randomly assigned to control, model (UC), UC + FMT, and UC + 5-ASA groups. Each group consisted of five mice. The establishment of the mouse model was verified by fecal occult-blood screening and hematoxylin–eosin staining. Results showed that fecal microbiota transplantation reduced colonic inflammation, significantly decreased T helper (Th)1 and Th17 cells, interferon-gamma, interleukin-2 and interleukin-17, as well as significantly increased Th2 and regulatory T (Treg) cells, interleukin-4, interleukin-10, and transforming growth factor-beta, and improved routine blood count. Furthermore, 16S rRNA gene-sequencing analysis showed a significant increase in the relative abundance of genus Akkermansia and a significant decrease in the relative abundance of genus Helicobacter in the ulcerative colitis group. Fecal microbiota transplantation restored the profile of the intestinal microbiota to that of the control group. These findings demonstrated the capability of fecal microbiota transplantation in controlling experimentally induced ulcerative colitis by improving Th1/Th2 and Th17/Treg imbalance through the regulation of intestinal microbiota.

scholarly journals Long-term efficacy and safety of single fecal microbiota transplantation for recurrent active ulcerative colitis

2020 ◽  
Author(s):  
Haiming Fang ◽  
Lian Fu ◽  
Xuejun Li ◽  
Jiajia Wang ◽  
Kangwei Xiong ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Adverse Events ◽  
Relative Abundance ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Efficacy And Safety ◽  
Long Term Follow Up ◽  
Initial Responder

AbstractAimsTo assess the long-term safety and efficacy of single fecal microbiota transplantation (FMT) for recurrent ulcerative colitis (UC).Methods20 UC patients were randomly divided into single FMT (n=10) and standard of care (SOC) (n=10) group. Patients in FMT group were just treated with single fresh FMT. Patients in SOC group with mild to moderate UC were treated with mesalazine, those with severe UC were given corticosteroids-induced remission, mesalazine maintenance treatment. The primary endpoint was clinical and mucosal remission at week 8. The second endpoint was the maintenance of clinical and mucosal remission, and possible adverse events during the long term follow up (12 to 24 months).Results90% (9/10) patients in FMT group and50% (5 /10)in SOC group could achieve primary endpoint at week-8.After 12 months of follow-up, 66.7% (6/9) FMT initial responder and 80.0% (4/5) SOC initial responder could maintain remission.5 FMT initial responder recipients and5SOC initial responder completed 24-months follow up and mainly could maintain remission [FMT vs SOC580% (4/5) vs 60% (3/5)].No adverse events occurred post FMT during long-term follow-up. At Phylum level, Bacteroidetes, Firmicutes and Proteobacteria were the dominant bacteria of gut microbiota in active UC patients. Compared with donor, the relative abundance of Bacteroidetes decreased and Proteobacteria increased significantly in active UC patients, Firmicutes showed no significant changes. Single fresh FMT could effectively reconstruct the composition of gut microbiota in active UC and maintain stability level with increased Bacteroidetes and decreased Proteobacteria abundance. FMT significantly reduced the relative abundance of Escherichia and increased the relative abundance of Prevotella at genera level. Pyruvate metabolism, glyoxylate and dicarboxylate metabolism, pantothenate and CoA biosynthesis showed significantly differences.ConclusionsSingle fresh FMT is an effective and safe strategy to induce long-term remission in patients with active UC and could be expected to be an alternative induction therapy for recurrent UC, even primary UC.What does this paper add to the literature?FMT is an effective and safe therapy for UC. However, long-term efficacy and safety of a single FMT was very limited. The present study found that a single fresh FMT could induce long-term remission in UC with no drugs need and could be expected to be an alternative induction therapy for recurrent UC, even primary UC

scholarly journals Fecal microbiota transplantation in refractory ulcerative colitis – a case report

2019 ◽  
Vol 47 (2) ◽  
pp. 1072-1079 ◽  
Author(s):  
B. D. Moutinho ◽  
J. P. Baima ◽  
F. F. Rigo ◽  
R. Saad-Hossne ◽  
J. Rodrigues ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fecal Microbiota Transplantation ◽  
Present Report ◽  
Therapeutic Option ◽  
Alternative Therapy ◽  
Fecal Microbiota ◽  
Clinical Activity ◽  
Microbial Composition ◽  
Inflammatory Bowel ◽  
And Function

Studies comparing gut microbiota profiles of inflammatory bowel disease (IBD) patients have shown several changes in microbiota composition, with marked reduction of local biodiversity relative to that of healthy controls. Modulation of the bacterial community is a promising strategy to reduce the proportion of harmful microorganisms and increase the proportion of beneficial bacteria; this is expected to prevent or treat IBD. The exact mechanism of fecal microbiota transplantation (FMT) remains unknown; however, replacing the host microbiota can reestablish gut microbial composition and function in IBD patients. The present report describes an ulcerative colitis patient who underwent FMT. A 17-year-old male with moderate to severe clinical activity, which was refractory to mesalazine, azathioprine, and infliximab, underwent FMT as alternative therapy. The patient exhibited clinical improvement after the procedure; however, the symptoms returned. A second FMT was performed 8 months after the first procedure, but the patient did not improve. In conclusion, despite the FMT failure observed in this patient, the procedure is a promising therapeutic option for IBD patients, and more in-depth studies of this method are needed.

P168 BACTEROIDETES SPECIES ARE USEFUL BIOMARKER OF CLINICAL ACTIVITY IN ULCERATIVE COLITIS

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S39-S39
Author(s):  
Kei Nomura ◽  
Dai Ishikawa ◽  
Koki Okahara ◽  
Shoko Ito ◽  
Masahito Takahashi ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Relative Abundance ◽  
Mayo Clinic ◽  
Activity Index ◽  
Illumina Miseq ◽  
Clinical Activity ◽  
Fecal Samples ◽  
Clinical Evaluations ◽  
Sum Score ◽  
Colon And Rectum

Abstract Background We previously reported that there were 13 species of Bacteroidetes phylum with significantly higher or lower relative abundance in patients with ulcerative colitis (UC) than healthy individuals. In this study, we investigated the correlation between Bacteroidetes species components in fecal samples and clinical evaluations of UC. Method This study included participants above 20 years of age. Fecal samples were collected for microbial analysis from 54 patients who had active UC based on a Lichtiger’s clinical activity index (CAI) ≥ 4 or an endoscopic Mayo clinic score ≥1. DNA was extracted from the fecal samples and analyzed by next-generation sequencing (the Illumina MiSeq sequencing system) targeting hsp60. We verified associations between Bacteroidetes species and eMayo sum score (total of endoscopic Mayo clinic scores in each intestine: periphery of appendix vermiformis, cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum), Robarts Histopathology Index (RHI), and CAI. Results Bacteroides uniformis (R = -0.44, p = 0.002) and four others significantly correlated with eMayo sum score. Alistipes shahii (R = -0.35, p = 0.02) and three others significantly correlated with RHI. Bacteroides rodentium (R = -0.37, p = 0.006) and two others significantly correlated with CAI. Furthermore, three Bacteroidetes species (Bacteroides stercoris, Bacteroides uniformis, and Parabacteroides merdae) correlated with two of three clinical evaluations, and the total relative abundance of these three species showed stronger correlation with eMayo sum score (R = -0.52, p = 0.00007). Conclusion All eight Bacteroidetes species identified in this study represented negative correlation with the clinical activity, so these species are suggested to be lost by exacerbation. Bacteroidetes species, especially total relative abundance of three Bacteroidetes species (Bacteroides stercoris, Bacteroides uniformis, and Parabacteroides merdae) may become a biomarker for evaluating the clinical activity of UC.

scholarly journals Fecal microbiota dynamics during disease activity and remission in newly diagnosed and established ulcerative colitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lena Öhman ◽  
Anders Lasson ◽  
Anna Strömbeck ◽  
Stefan Isaksson ◽  
Marcus Hesselmar ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Disease Activity ◽  
Temporal Dynamics ◽  
Fecal Microbiota ◽  
Disease Stage ◽  
Dietary Interventions ◽  
Microbial Composition ◽  
Fecal Samples ◽  
Specific Species

AbstractPatients with ulcerative colitis (UC) have an altered gut microbiota composition, but the microbial relationship to disease activity needs to be further elucidated. Therefore, temporal dynamics of the fecal microbial community during remission and flare was determined. Fecal samples were collected at 2–6 time-points from UC patients during established disease (cohort EST) and at diagnosis (cohort NEW). Sampling range for cohort EST was 3–10 months and for cohort NEW 36 months. Relapses were monitored for an additional three years for cohort EST. Microbial composition was assessed by Genetic Analysis GA-map Dysbiosis Test, targeting ≥ 300 bacteria. Eighteen patients in cohort EST (8 with maintained remission and 10 experiencing a flare), provided 71 fecal samples. In cohort NEW, 13 patients provided 49 fecal samples. The microbial composition showed no clustering related to disease activity in any cohort. Microbial dissimilarity was higher between than within patients for both cohorts, irrespective of presence of a flare. Microbial stability within patients was constant over time with no major shift in overall composition nor modification in the abundance of any specific species. Microbial composition was not affected by intensified medical treatment or linked to future disease course. Thus in UC, the gut microbiota is highly stable irrespective of disease stage, disease activity or treatment escalation. This suggests that prolonged dietary interventions or repeated fecal transplantations are needed to be able to induce permanent alterations of the gut microbiota.

scholarly journals Fecal Microbiota Transplant in Two Ulcerative Colitis Pediatric Cases: Gut Microbiota and Clinical Course Correlations

2020 ◽  
Vol 8 (10) ◽  
pp. 1486
Author(s):  
Andrea Quagliariello ◽  
Federica Del Chierico ◽  
Sofia Reddel ◽  
Alessandra Russo ◽  
Andrea Onetti Muda ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Clinical Effects ◽  
Phylogenetic Distance ◽  
Fecal Microbiota Transplant ◽  
Inflammatory Bowel ◽  
Clinical Conditions ◽  
And Control

Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- and post-FMT monitored for clinical conditions and gut bacterial ecology. Microbiota profiling relied on receipts’ time-point profiles, donors and control cohorts’ baseline descriptions. After FMT, the improvement of clinical conditions was recorded for both patients. After 12 months, the mild UC patient was in clinical remission, while the moderate UC patient, after 12 weeks, had a clinical worsening. Ecological analyses highlighted an increase in microbiota richness and phylogenetic distance after FMT. This increase was mainly due to Collinsella aerofaciens and Eubacterium biforme, inherited by respective donors. Moreover, a decrease of Proteus and Blautia producta, and the increment of Parabacteroides, Mogibacteriaceae, Bacteroides eggerthi, Bacteroides plebeius, Ruminococcus bromii, and BBacteroidesovatus were associated with remission of the patient’s condition. FMT results in a long-term response in mild UC, while in the moderate form there is probably need for multiple FMT administrations. FMT leads to a decrease in potential pathogens and an increase in microorganisms correlated to remission status.

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