scholarly journals P679 The keystone bacterium Christensenella minuta improves colitis in in vivo preclinical Inflammatory Bowel Disease models

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S600-S600
Author(s):  
C Kropp ◽  
K Le Corf ◽  
K Relizani ◽  
K Tambosco ◽  
C Martinez ◽  
...  

Abstract Background There is increasing evidence that microbiome-based therapies can correct dysbiosis and reduce inflammation associated with Inflammatory Bowel Diseases (IBD). In particular, the human commensal family of Christensenellaceae bacteria has been reported as missing in several cohorts of Crohn’s disease patients, indicating that it may have a role in maintaining microbial symbiosis in this population. To assess its potential for IBD management, we used the reference type species Christensenella minuta DSM 22607 to examine its anti-inflammatory properties. Methods We first performed two distinct independent preclinical colitis models: i) a moderate DNBS-induced colitis model in mice and ii) a severe TNBS-induced colitis model in rats. To decipher the mechanisms of action of C. minuta underlying the observed effects, we determined its ability to produce short chain fatty acids (SCFA) at different growth phases and we assessed its capacity to modulate the inflammatory response of human colonic cells. Results Our results showed that in both rodent models, C. minuta prevented intestinal damages by decreasing macroscopic scores, reduced colonic inflammation by limiting neutrophils infiltration in the colon and stimulated mucosal healing. We also confirmed that C. minuta is a high acetate and moderate butyrate producer. Finally, we showed that C. minuta displayed potent anti-inflammatory properties by decreasing the secretion of the pro-inflammatory cytokine IL-8 through NF-kB inhibition in HT-29 cells. Conclusion Together, these results revealed for the first time the strong anti-inflammatory properties of C. minuta and confirm its high potential as an innovative microbiome-based biotherapy for IBD.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Camille Kropp ◽  
Katy Le Corf ◽  
Karima Relizani ◽  
Kevin Tambosco ◽  
Ccori Martinez ◽  
...  

AbstractChristensenellaceae is a family of subdominant commensal bacteria found in humans. It is thought to play an important role in gut health by maintaining microbial symbiosis. Indeed, these bacteria occur at significantly lower levels or are absent in individuals suffering from inflammatory bowel diseases (IBDs). Here, we explored if type species Christensenella minuta (strain: DSM 22607) could have the potential to help treat IBDs. We assessed key properties displayed by the bacterium using a combination of in vitro and in vivo assays. We found that while C. minuta is a strict anaerobe, it is also oxygen tolerant. Additionally, we observed that the species produces high levels of acetate and moderate levels of butyrate. We performed deep phenotyping using Biolog microarrays. Using human intestinal cell lines, we discovered that C. minuta demonstrated strong anti-inflammatory activity, resulting in reduced levels of proinflammatory IL-8 cytokines via the inhibition of the NF-κB signaling pathway. Furthermore, C. minuta protected intestinal epithelial integrity in vitro. Finally, in two distinct animal models of acute colitis, C. minuta prevented intestinal damage, reduced colonic inflammation, and promoted mucosal healing. Together, these results indicate that C. minuta has potent immunomodulatory properties, underscoring its potential use in innovative microbiome-based IBD biotherapies.


2021 ◽  
Vol 14 (6) ◽  
pp. 506
Author(s):  
Daan V. Bunt ◽  
Adriaan J. Minnaard ◽  
Sahar El Aidy

A disturbed interaction between the gut microbiota and the mucosal immune system plays a pivotal role in the development of inflammatory bowel disease (IBD). Various compounds that are produced by the gut microbiota, from its metabolism of diverse dietary sources, have been found to possess anti-inflammatory and anti-oxidative properties in in vitro and in vivo models relevant to IBD. These gut microbiota-derived metabolites may have similar, or more potent gut homeostasis-promoting effects compared to the widely-studied short-chain fatty acids (SCFAs). Available data suggest that mainly members of the Firmicutes are responsible for producing metabolites with the aforementioned effects, a phylum that is generally underrepresented in the microbiota of IBD patients. Further efforts aiming at characterizing such metabolites and examining their properties may help to develop novel modulatory microbiome therapies to treat or prevent IBD.


2021 ◽  
Author(s):  
Xiao fan Song ◽  
Lei Qiao ◽  
Shuqi Yan ◽  
Yue Chen ◽  
Xina Dou ◽  
...  

Selenium (Se) as an essential micronutrient that has implications in human diseases, including inflammatory bowel disease (IBD), especially with respect to Se deficiencies. Recently, selenium nanoparticles (SeNPs) have attracted significant...


2021 ◽  
Vol 14 ◽  
pp. 175628482110056
Author(s):  
Virginia Solitano ◽  
Ferdinando D’Amico ◽  
Mariangela Allocca ◽  
Gionata Fiorino ◽  
Alessandra Zilli ◽  
...  

The potential of endoscopic evaluation in the management of inflammatory bowel diseases (IBD) has undoubtedly grown over the last few years. When dealing with IBD patients, histological remission (HR) is now considered a desirable target along with symptomatic and endoscopic remission, due to its association with better long-term outcomes. Consequently, the ability of endoscopic techniques to reflect microscopic findings in vivo without having to collect biopsies has become of upmost importance. In this context, a more accurate evaluation of inflammatory disease activity and the detection of dysplasia represent two mainstay targets for IBD endoscopists. New diagnostic technologies have been developed, such as dye-less chromoendoscopy, endomicroscopy, and molecular imaging, but their real incorporation in daily practice is not yet well defined. Although dye-chromoendoscopy is still recommended as the gold standard approach in dysplasia surveillance, recent research questioned the superiority of this technique over new advanced dye-less modalities [narrow band imaging (NBI), Fuji intelligent color enhancement (FICE), i-scan, blue light imaging (BLI) and linked color imaging (LCI)]. The endoscopic armamentarium might also be enriched by new video capsule endoscopy for monitoring disease activity, and high expectations are placed on the application of artificial intelligence (AI) systems to reduce operator-subjectivity and inter-observer variability. The goal of this review is to provide an updated insight on contemporary knowledge regarding new endoscopic techniques and devices, with special focus on their role in the assessment of disease activity and colorectal cancer surveillance.


Author(s):  
Armando Tripodi ◽  
Luisa Spina ◽  
Laura Francesca Pisani ◽  
Lidia Padovan ◽  
Flaminia Cavallaro ◽  
...  

Abstract Background Inflammatory bowel diseases (IBD) are characterized by an increased thrombosis risk of uncertain etiology. Coagulation derangement arising from inflammation may be a triggering factor. We hypothesized that strong inflammation inhibitors (eg, anti-tumor necrosis factor-α drugs) may affect coagulation. Methods Forty patients with IBD were compared with 57 control patients for coagulation factors and endogenous thrombin potential (ETP), the latter being the most sensitive marker of in vivo pro- and anticoagulation balance. We measured ETP in the presence and absence of thrombomodulin (the physiologic protein C [PC] activator). Coagulation at different timepoints was also assessed for 28 of these patients during infliximab treatment. Results The median ETP (nM thrombin × minutes) and range (minimum-maximum) were each higher in patients at baseline than in control patients in both the absence (2120 [1611-3041] vs 1865 [1270-2337]) and the presence (1453 [464-2522] vs 831 [104-1741]) of thrombomodulin. The ETP ratio (with/without thrombomodulin) was high at baseline (0.73 [0.21-0.90] vs 0.45 [0.07-0.85]). The ETP and ETP ratio declined during treatment and were significantly lower at the end than at baseline. Factor (F) VIII and fibrinogen, which were high at baseline, decreased during treatment and at the end were significantly lower than at baseline. The FVIII/PC ratio, which was high in patients at baseline, declined during treatment and at the end was lower than at baseline. C-reactive protein recorded at the end of treatment was lower than at baseline. Conclusions Patients with IBD have a procoagulant imbalance as shown by increased ETP at baseline. The ETP decreases during treatment with infliximab, which is related to decreased FVIII and FVIII/PC ratio. This effect is also related to the improvement of inflammation as shown by decreased fibrinogen and C-reactive protein.


2020 ◽  
Vol 21 (8) ◽  
pp. 2940
Author(s):  
Antonelly Cassio Alves de Carvalho ◽  
Gabriela Achete de Souza ◽  
Samylla Vaz de Marqui ◽  
Élen Landgraf Guiguer ◽  
Adriano Cressoni Araújo ◽  
...  

Inflammatory bowel diseases (IBD) are characterized by a chronic and recurrent gastrointestinal condition, including mainly ulcerative colitis (UC) and Crohn’s disease (CD). Cannabis sativa (CS) is widely used for medicinal, recreational, and religious purposes. The most studied compound of CS is tetrahydrocannabinol (THC) and cannabidiol (CBD). Besides many relevant therapeutic roles such as anti-inflammatory and antioxidant properties, there is still much controversy about the consumption of this plant since the misuse can lead to serious health problems. Because of these reasons, the aim of this review is to investigate the effects of CS on the treatment of UC and CD. The literature search was performed in PubMed/Medline, PMC, EMBASE, and Cochrane databases. The use of CS leads to the improvement of UC and CD scores and quality of life. The medical use of CS is on the rise. Although the literature shows relevant antioxidant and anti-inflammatory effects that could improve UC and CD scores, it is still not possible to establish a treatment criterion since the studies have no standardization regarding the variety and part of the plant that is used, route of administration and doses. Therefore, we suggest caution in the use of CS in the therapeutic approach of IBD until clinical trials with standardization and a relevant number of patients are performed.


Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 67 ◽  
Author(s):  
Shara Francesca Rapa ◽  
Rosanna Di Paola ◽  
Marika Cordaro ◽  
Rosalba Siracusa ◽  
Ramona D’Amico ◽  
...  

Intestinal epithelial barrier impairment plays a key pathogenic role in inflammatory bowel diseases (IBDs). In particular, together with oxidative stress, intestinal epithelial barrier alteration is considered as upstream event in ulcerative colitis (UC). In order to identify new products of natural origin with a potential activity for UC treatment, this study evaluated the effects of plumericin, a spirolactone iridoid, present as one of the main bioactive components in the bark of Himatanthus sucuuba (Woodson). Plumericin was evaluated for its ability to improve barrier function and to reduce apoptotic parameters during inflammation, both in intestinal epithelial cells (IEC-6), and in an animal experimental model of 2, 4, 6-dinitrobenzene sulfonic acid (DNBS)-induced colitis. Our results indicated that plumericin increased the expression of adhesion molecules, enhanced IEC-6 cells actin cytoskeleton rearrangement, and promoted their motility. Moreover, plumericin reduced apoptotic parameters in IEC-6. These results were confirmed in vivo. Plumericin reduced the activity of myeloperoxidase, inhibited the expression of ICAM-1, P-selectin, and the formation of PAR, and reduced apoptosis parameters in mice colitis induced by DNBS. These results support a pharmacological potential of plumericin in the treatment of UC, due to its ability to improve the structural integrity of the intestinal epithelium and its barrier function.


Author(s):  
Mingzhu Luan ◽  
Huiyun Wang ◽  
Jiazhen Wang ◽  
Xiaofan Zhang ◽  
Fenglan Zhao ◽  
...  

: In vivo and in vitro studies reveal that ursolic acid (UA) is able to counteract endogenous and exogenous inflammatory stimuli, and has favorable anti-inflammatory effects. The anti-inflammatory mechanisms mainly include decreasing the release of histamine in mast cells, suppressing the activities of lipoxygenase, cyclooxygenase and phospholipase, and reducing the production of nitric oxide and reactive oxygen species, blocking the activation of signal pathway, down-regulating the expression of inflammatory factors, and inhibiting the activities of elastase and complement. These mechanisms can open up new avenues for the scientific community to develop or improve novel therapeutic approaches to tackle inflammatory diseases such as arthritis, atherosclerosis, neuroinflammation, liver diseases, kidney diseases, diabetes, dermatitis, bowel diseases, cancer. The anti-inflammatory activity, the anti-inflammatory mechanism of ursolic acid and its therapeutic applications are reviewed in this paper.


2019 ◽  
Vol 44 (6) ◽  
pp. 595-605 ◽  
Author(s):  
Corinne E. Metzger ◽  
S. Anand Narayanan ◽  
David C. Zawieja ◽  
Susan A. Bloomfield

Inflammatory bowel disease is a condition that leads to gut pathologies such as abnormal lymphatic architecture, as well as to systemic comorbidities such as bone loss. Furthermore, current therapies are limited to low efficacy and incur side effects. Dietary interventions have been explored minimally, but may provide a treatment for improving gut outcomes and comorbidities. Indeed, plant-based soy protein has been shown to exert anti-inflammatory effects. Here, we tested the impact of a moderately elevated soy protein diet in a chronic, 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model on gut and bone inflammatory-mediated pathophysiological adaptations. Colitis was induced by intrarectal administration of TNBS. Gut histopathology was scored, and lymphatic structural changes and the local inflammatory state were assessed via immunofluorescence. In addition, the effects of gut inflammation on bone turnover and osteocyte proteins were determined via histomorphometry and immunohistochemistry, respectively. The moderately elevated soy protein diet produced improvements in both colonic and bone tissues. In TNBS animals given the soy protein intervention, colon histological scores were reduced and the abnormal lymphatic architecture resolved. There were also improvements in bone formation and reduced bone resorption. In addition, TNBS increased inflammatory cytokines such as tumor necrosis factor-α and receptor activator of nuclear factor κ-B ligand in the gut and bone, but this was resolved in both tissues with the dietary soy protein intervention. The moderately elevated soy protein diet mitigated gut and bone inflammation in a chronic, TNBS-induced colitis model, demonstrating the potential for soy protein as a potential anti-inflammatory dietary intervention for inflammatory bowel disease.


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