scholarly journals Discovery of a Novel Multi-Strains Probiotic Formulation with Improved Efficacy toward Intestinal Inflammation

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1945
Author(s):  
Michele Biagioli ◽  
Adriana Carino ◽  
Cristina Di Giorgio ◽  
Silvia Marchianò ◽  
Martina Bordoni ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Intestinal Inflammation ◽  
Signs And Symptoms ◽  
Streptococcus Thermophilus ◽  
The Novel ◽  
Beneficial Effects ◽  
Bifidobacterium Animalis ◽  
Chemical Models ◽  
Tnf Α ◽  
Inflammatory Bowel

Dysbiosis is commonly detected in patients with inflammatory bowel disease (IBD), supporting the concept that a dysregulated immune reaction to bacterial antigens has a pathogenic role in the development of intestinal inflammation. In the present study, we have investigated the beneficial effects of a novel probiotic formulation assembled by combining four probiotics (Streptococcus thermophilus, Lactobacillus casei, Bifidobacterium breve, Bifidobacterium animalis subsp. Lactis) with Bacillus subtilis, a Gram-positive bacterium, with extensive bio-applications. Mice rendered colitic by administration of TNBS or DSS were administered with Bacillus subtilis alone, Vivomixx® or the novel Five strains formulation. Vivomixx® attenuated the severity of inflammation and reduced the development of signs and symptoms of colitis in both models. Adding Bacillus subtilis to Vivomixx® improved the beneficial effects of the bacterial therapy. The novel Five strains formulation was as effective as Vivomixx® in reducing the development of signs and symptoms of colitis and reduced the expression of pro-inflammatory mediators including Il-6 and Tnf-α while increased the expression of Il-10 mRNA and the number of Treg. In summary, we have shown that a novel Five strains probiotics formulation exerts beneficial effects on two chemical models of colitis, establishing Bacillus subtilis as a probiotic in rodent models of inflammation.

scholarly journals Improving the Efficacy of Mesenchymal/Stromal-Based Therapy for Treatment of Inflammatory Bowel Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1507
Author(s):  
Mercedes Lopez-Santalla ◽  
Marina Inmaculada Garin
Keyword(s):  
Clinical Trials ◽  
Immune Responses ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
The Novel ◽  
Beneficial Effects ◽  
Commensal Microbiota ◽  
Bowel Diseases ◽  
Inflammatory Processes ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBD) consisting of persistent and relapsing inflammatory processes of the intestinal mucosa are caused by genetic, environmental, and commensal microbiota factors. Despite recent advances in clinical treatments aiming to decrease inflammation, nearly 30% of patients treated with biologicals experienced drawbacks including loss of response, while others can develop severe side effects. Hence, novel effective treatments are highly needed. Mesenchymal stem/stromal cell (MSCs) therapy is an innovative therapeutic alternative currently under investigation for IBD. MSCs have the inherent capacity of modulating inflammatory immune responses as well as regenerating damaged tissues and are therefore a prime candidate to use as cell therapy in patients with IBD. At present, MSC-based therapy has been shown preclinically to modulate intestinal inflammation, whilst the safety of MSC-based therapy has been demonstrated in clinical trials. However, the successful results in preclinical studies have not been replicated in clinical trials. In this review, we will summarize the protocols used in preclinical and clinical trials and the novel approaches currently under investigation which aim to increase the beneficial effects of MSC-based therapy for IBD.

Bidens pilosa (Black Jack) Standardized Extract Ameliorates Acute TNBS-induced Intestinal Inflammation in Rats

Planta Medica ◽  
2020 ◽  
Vol 86 (05) ◽  
pp. 319-330
Author(s):  
Ana E.V. Quaglio ◽  
Vinicius M. Cruz ◽  
Luiz D. Almeida-Junior ◽  
Celso A.R.A. Costa ◽  
Luiz C. Di Stasi
Keyword(s):  
Intestinal Inflammation ◽  
Gastric Ulcers ◽  
Bidens Pilosa ◽  
Tem Analysis ◽  
Beneficial Effects ◽  
Transmission Electron ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
Α Level

Abstract Bidens pilosa is an herb popularly used to treat inflammation, hemorrhoids, fever, and gastric ulcers with reported pharmacological activities and chemical composition that sustain its selection as a potential intestinal anti-inflammatory product. Based on this, we examined the effects of a B. pilosa fatty acid-standardized supercritical preparation on the intestinal inflammatory process induced by trinitrobenzenesulphonic acid in rats, using either preventative or curative treatments. We also investigated the safety of plant extract by acute and sub-chronic toxicological analysis. The intestinal anti-inflammatory activity was related to modulation of the immune response, increasing IL-10 production and reducing IL-1β, IL-6, and TNF-α level, the oxidative stress, and the MUC production in the inflamed colon. Optic, scanning, and transmission electron microscopy (TEM) analysis supported the beneficial effects promoted by B. pilosa, which were closely related to downregulation of heparanase, Hsp70, Mapk 3, and NF-κB signaling and with the presence of long-chain fatty acids in extract. Our data suggest that B. pilosa supercritical preparation is a chemically standardized preparation potentially useful as complementary intestinal anti-inflammatory agent to treat inflammatory bowel disease.

scholarly journals Review: Local Tumor Necrosis Factor-α Inhibition in Inflammatory Bowel Disease

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 539
Author(s):  
Bahez Gareb ◽  
Antonius T. Otten ◽  
Henderik W. Frijlink ◽  
Gerard Dijkstra ◽  
Jos G. W. Kosterink
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Genetically Modified Organisms ◽  
Intestinal Inflammation ◽  
Systemic Exposure ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Necrosis Factor

Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by intestinal inflammation. Increased intestinal levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) are associated with disease activity and severity. Anti-TNF-α therapy is administered systemically and efficacious in the treatment of IBD. However, systemic exposure is associated with adverse events that may impede therapeutic treatment. Clinical studies show that the efficacy correlates with immunological effects localized in the gastrointestinal tract (GIT) as opposed to systemic effects. These data suggest that site-specific TNF-α inhibition in IBD may be efficacious with fewer expected side effects related to systemic exposure. We therefore reviewed the available literature that investigated the efficacy or feasibility of local TNF-α inhibition in IBD. A literature search was performed on PubMed with given search terms and strategy. Of 8739 hits, 48 citations were included in this review. These studies ranged from animal studies to randomized placebo-controlled clinical trials. In these studies, local anti-TNF-α therapy was achieved with antibodies, antisense oligonucleotides (ASO), small interfering RNA (siRNA), microRNA (miRNA) and genetically modified organisms. This narrative review summarizes and discusses these approaches in view of the clinical relevance of local TNF-α inhibition in IBD.

scholarly journals Chronic colitis-induced visceral pain is associated with increased anxiety during quiescent phase

2019 ◽  
Vol 316 (6) ◽  
pp. G692-G700 ◽  
Author(s):  
Emmeline Salameh ◽  
Mathieu Meleine ◽  
Guillaume Gourcerol ◽  
Jean-Claude do Rego ◽  
Jean-Luc do Rego ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Visceral Pain ◽  
Myeloperoxidase Activity ◽  
Therapeutic Approaches ◽  
Chronic Colitis ◽  
Functional Symptoms ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Novel Therapeutic

Inflammatory bowel diseases (IBD) are characterized by repetition of flares and remission periods leading to chronic postinflammatory sequelae. Among postinflammatory sequelae, one-third of patients with IBD are suffering from functional symptoms or psychological comorbidities that persist during remission. The aim of our study was to assess functional and behavioral sequelae of chronic colitis in rats with quiescent intestinal inflammation. Chronic colitis was induced by a weekly intrarectal injection of increasing concentrations of trinitrobenzene sulfonic acid (TNBS) for 3 wk (15–45 mg of TNBS) in 30 rats, whereas the control rats ( n = 24) received the vehicle. At 50 days post-TNBS, visceral sensitivity was assessed by visceromotor response to colorectal distension, and transient receptor potential vanilloid type 1 (TRPV1) expression was also quantified in the colon and dorsal root ganglia. Barrier function and inflammatory response were assessed by studying intestinal permeability, tight junction protein, myeloperoxidase activity, histological score, and cytokine production (IL-6, IL-10, and TNF-α). Anxiety behavioral tests were performed from 50 to 64 days after the last TNBS injection. Chronic TNBS induced 1) a visceral hypersensitivity ( P = 0.03), 2) an increased colon weight-to-length ratio ( P = 0.01), 3) higher inflammatory and fibrosis scores ( P = 0.0390 and P = 0.0016, respectively), and 4) a higher colonic IL-6 and IL-10 production ( P = 0.008 and P = 0.005, respectively) compared with control rats. Intestinal permeability, colonic production of TNF-α, myeloperoxidase activity, and TRPV1 expression did not differ among groups. Chronic TNBS increased anxiety-related behavior in the open-field test and in the acoustic stress test. In conclusion, chronic colitis induced functional sequelae such as visceral hypersensitivity and increased anxiety with a low-grade intestinal inflammation. Development of a representative animal model will allow defining novel therapeutic approaches to achieve a better management of IBD-related sequelae.NEW & NOTEWORTHY Patients with inflammatory bowel diseases have impaired quality of life. Therapeutic progress to control mucosal inflammation provides us an opportunity to develop novel approaches to understand mechanisms behind postinflammatory sequelae. We used a chronic colitis model to study long-term sequelae on visceral pain, gut barrier function, and psychological impact. Chronic colitis induced functional symptoms and increased anxiety in the remission period. It might define novel therapeutic approaches to achieve a better inflammatory bowel disease-related sequelae management.

scholarly journals Regnase-1 controls colon epithelial regeneration via regulation of mTOR and purine metabolism

2018 ◽  
Vol 115 (43) ◽  
pp. 11036-11041 ◽  
Author(s):  
Yasuharu Nagahama ◽  
Mayuko Shimoda ◽  
Guoliang Mao ◽  
Shailendra Kumar Singh ◽  
Yuuki Kozakai ◽  
...  
Keyword(s):  
Acute Inflammation ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Body Weight Loss ◽  
Purine Metabolism ◽  
Intestinal Epithelial ◽  
Beneficial Effects ◽  
Epithelial Regeneration ◽  
Mtorc1 Signaling ◽  
Inflammatory Bowel

Damage to intestinal epithelial cell (IEC) layers during intestinal inflammation is associated with inflammatory bowel disease. Here we show that the endoribonuclease Regnase-1 controls colon epithelial regeneration by regulating protein kinase mTOR (the mechanistic target of rapamycin kinase) and purine metabolism. During dextran sulfate sodium-induced intestinal epithelial injury and acute colitis, Regnase-1∆IEC mice, which lack Regnase-1 specifically in the intestinal epithelium, were resistant to body weight loss, maintained an intact intestinal barrier, and showed increased cell proliferation and decreased epithelial apoptosis. Chronic colitis and tumor progression were also attenuated in Regnase-1∆IEC mice. Regnase-1 predominantly regulates mTORC1 signaling. Metabolic analysis revealed that Regnase-1 participates in purine metabolism and energy metabolism during inflammation. Furthermore, increased expression of ectonucleotidases contributed to the resolution of acute inflammation in Regnase-1∆IEC mice. These findings provide evidence that Regnase-1 deficiency has beneficial effects on the prevention and/or blocking of intestinal inflammatory disorders.

scholarly journals Phosphatase Shp2 exacerbates intestinal inflammation by disrupting macrophage responsiveness to interleukin-10

2019 ◽  
Vol 216 (2) ◽  
pp. 337-349 ◽  
Author(s):  
Peng Xiao ◽  
Huilun Zhang ◽  
Yu Zhang ◽  
Mingzhu Zheng ◽  
Rongbei Liu ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Interleukin 10 ◽  
Blood Monocytes ◽  
Stat3 Signaling ◽  
Tnf Α ◽  
Mouse Macrophages ◽  
Inflammatory Bowel ◽  
Anti Inflammatory ◽  
Further Development

Inflammatory cytokines produced by activated macrophages largely contribute to the pathological signs of inflammatory bowel disease (IBD). Interleukin-10 (IL-10) is the predominant anti-inflammatory cytokine in the intestine, and its therapeutic efficacy for IBD has been clinically tested. Nevertheless, how the function of IL-10 is regulated in the intestinal microenvironment remains unknown, which largely hinders the further development of IL-10–based therapeutic strategies. Here, we found that the expression of phosphatase Shp2 was increased in colonic macrophages and blood monocytes from IBD patients compared with those from healthy controls. Shp2 deficiency in macrophages protects mice from colitis and colitis-driven colon cancer. Mechanistically, Shp2 disrupts IL-10–STAT3 signaling and its dependent anti-inflammatory response in human and mouse macrophages. Furthermore, a Shp2-inducing role of TNF-α is unveiled in our study. Collectively, our work identifies Shp2 as a detrimental factor for intestinal immune homeostasis and hopefully will be helpful in the future exploitation of IL-10 immunotherapy for IBD.

scholarly journals Recent Advances: The Imbalance of Cytokines in the Pathogenesis of Inflammatory Bowel Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Qingdong Guan ◽  
Jiguo Zhang
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Inflammatory Cytokines ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Beneficial Effects ◽  
Recent Advances ◽  
Inflammatory Bowel ◽  
Inflammation Targeting ◽  
Anti Inflammatory

Cytokines play an important role in the immunopathogenesis of inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, where they drive and regulate multiple aspects of intestinal inflammation. The imbalance between proinflammatory and anti-inflammatory cytokines that occurs in IBD results in disease progression and tissue damage and limits the resolution of inflammation. Targeting cytokines have been novel strategies in the treatment of IBD. Recent studies show the beneficial effects of anticytokine treatments to IBD patients, and multiple novel cytokines are found to be involved in the pathogenesis of IBD. In this review, we will discuss the recent advances of novel biologics in clinics and clinical trials, and novel proinflammatory and anti-inflammatory cytokines found in IBD with focusing on IL-12 family and IL-1 family members as well as their relevance to the potential therapy of IBD.

Apple peel polyphenols: a key player in the prevention and treatment of experimental inflammatory bowel disease

2016 ◽  
Vol 130 (23) ◽  
pp. 2217-2237 ◽  
Author(s):  
Marie-Claude Denis ◽  
Denis Roy ◽  
Pantea Rahmani Yeganeh ◽  
Yves Desjardins ◽  
Thibault Varin ◽  
...  
Keyword(s):  
Fruits And Vegetables ◽  
Intestinal Inflammation ◽  
Therapeutic Effects ◽  
Microbial Composition ◽  
Beneficial Effects ◽  
Apple Peel ◽  
Bowel Diseases ◽  
Clinical Benefits ◽  
Inflammatory Bowel ◽  
Underlying Mechanisms

Diets rich in fruits and vegetables may reduce oxidative stress (OxS) and inflammation via several mechanisms. These beneficial effects may be due to their high polyphenol content. The aims of the present study are to evaluate the preventive and therapeutic aspects of polyphenols in dried apple peel powder (DAPP) on intestinal inflammation while elucidating the underlying mechanisms and clinical benefits. Induction of intestinal inflammation in mice was performed by oral administration of the inflammatory agent dextran sulfate sodium (DSS) at 2.5% for 10 days. Physiological and supraphysiological doses of DAPP (200 and 400 mg/kg/day respectively) were administered by gavage for 10 days pre- and post-DSS treatment. DSS-mediated inflammation caused weight loss, shortening of the colon, dystrophic detachment of the epithelium, and infiltration of mono- and poly-morphonuclear cells in the colon. DSS induced an increase in lipid peroxidation, a down-regulation of antioxidant enzymes, an augmented expression of myeloperoxidase (MPO) and cyclooxygenase-2 (COX-2), an elevated production of prostaglandin E2 (PGE2) and a shift in mucosa-associated microbial composition. However, DAPP normalized most of these abnormalities in preventive or therapeutic situations in addition to lowering inflammatory cytokines while stimulating antioxidant transcription factors and modulating other potential healing pathways. The supraphysiological dose of DAPP in therapeutic situations also improved mitochondrial dysfunction. Relative abundance of Peptostreptococcaceae and Enterobacteriaceae bacteria was slightly decreased in DAPP-treated mice. In conclusion, DAPP exhibits powerful antioxidant and anti-inflammatory action in the intestine and is associated with the regulation of cellular signalling pathways and changes in microbiota composition. Evaluation of preventive and therapeutic effects of DAPP may be clinically feasible in individuals with intestinal inflammatory bowel diseases.

scholarly journals Animal models for inducing inflammatory bowel diseases: integrative review

2021 ◽  
Vol 11 (1) ◽  
pp. 80-87
Author(s):  
Nadja Maria da Costa Melo ◽  
Marília Virgo Silva Almeida ◽  
Daniel Melo de Oliveira Campos ◽  
Claudio Bruno Silva de Oliveira ◽  
Jonas Ivan Nobre Oliveira
Keyword(s):  
Acetic Acid ◽  
Animal Models ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Integrative Review ◽  
Chemical Models ◽  
Experimental Induction ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Colitis Model

Objective: To identify and describe comparatively the chemical models of the induction of inflammatory bowel diseases (IBD) in rodents most used and that best mimic the pathogenesis in humans. Methods: Based on an integrative review in the MEDLINE and LILACS databases, it was investigated which experimental induction models were most cited in articles published from 2004 to 2020, with the descriptors "Colitis/CI", "Colitis model ulcerative" and "Intestinal inflammation model." All empirical articles that addressed one or more inflammation models in rats or mice were included. Results: 239 articles were identified; of these, only ten empirical articles were selected. The most used models were colitis induced by TNBS acid, DSS, and colitis induced by acetic acid (AA). Conclusion: It was possible to identify the most used models to promote the induction of intestinal inflammation in rats, and both models proved to be effective according to the limitations observed in the models described, suggesting the need for new works that use more well-defined protocols and that more fully represent the pathophysiological complexity of the disease.

scholarly journals Immunomodulatory role of Parkinson’s disease 7 in inflammatory bowel disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rita Lippai ◽  
Apor Veres-Székely ◽  
Erna Sziksz ◽  
Yoichiro Iwakura ◽  
Domonkos Pap ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Inflammatory Bowel Disease ◽  
Parkinson's Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Ht 29

AbstractRecently the role of Parkinson’s disease 7 (PARK7) was studied in gastrointestinal diseases, however, the complex role of PARK7 in the intestinal inflammation is still not completely clear. Expression and localization of PARK7 were determined in the colon biopsies of children with inflammatory bowel disease (IBD), in the colon of dextran sodium sulphate (DSS) treated mice and in HT-29 colonic epithelial cells treated with interleukin (IL)-17, hydrogen peroxide (H2O2), tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β or lipopolysaccharide (LPS). Effect of PARK7 on the synthesis of IBD related cytokines was determined using PARK7 gene silenced HT-29 cells and 3,4,5-trimethoxy-N-(4-(8-methylimidazo(1,2-a)pyridine-2-yl)phenyl)benzamide (Comp23)—compound increasing PARK7 activity—treated mice with DSS-colitis. PARK7 expression was higher in the mucosa of children with Crohn’s disease compared to that of controls. While H2O2 and IL-17 treatment increased, LPS, TNF-α or TGF-β treatment decreased the PARK7 synthesis of HT-29 cells. PARK7 gene silencing influenced the synthesis of IL1B, IL6, TNFA and TGFB1 in vitro. Comp23 treatment attenuated the ex vivo permeability of colonic sacs, the clinical symptoms, and mucosal expression of Tgfb1, Il1b, Il6 and Il10 of DSS-treated mice. Our study revealed the role of PARK7 in the regulation of IBD-related inflammation in vitro and in vivo, suggesting its importance as a future therapeutic target.

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