scholarly journals Prevotella copri is associated with carboplatin-induced gut toxicity

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Chaoheng Yu ◽  
Bailing Zhou ◽  
Xuyang Xia ◽  
Shuang Chen ◽  
Yun Deng ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Inflammatory Cells ◽  
Mucosal Injury ◽  
Mucosal Damage ◽  
Pathological Process ◽  
Cancer Drug ◽  
Gut Toxicity ◽  
Junction Protein ◽  
Intestinal Mucositis ◽  
Intestinal Mucosal Injury

Abstract As a widely used cancer drug, carboplatin often results in serious side effects, such as gut toxicity. In this study, we examined the effects of gut microbiota on mice with carboplatin-induced intestinal mucosal damage. Carboplatin resulted in intestinal mucositis, as indicated by weight loss, diarrhoea, and infiltration of inflammatory cells. It markedly increased the expression of inflammatory cytokines/chemokines in intestine. Carboplatin also altered the diversity and composition of the gut microbiota. A significantly higher abundance of Prevotella copri (P. copri) was observed in carboplatin-treated mice. Moreover, the content of P. copri was positively correlated with the severity of intestinal mucositis. Pretreatment with metronidazole reduced the content of P. copri and relieved the intestinal mucosal injury and inflammation that was induced by carboplatin. Further study revealed that supplementation with P. copri in carboplatin-treated mice resulted in more severe tissue damage, lower tight junction protein expression and higher cytokine expression, and it enhanced both local and systemic immune responses. These data demonstrated that P. copri was involved in the pathological process of carboplatin-induced intestinal mucositis, suggesting a potential attenuation of carboplatin-induced intestinal mucositis by targeting P. copri.

Dietary fucoidan of Acaudina molpadioides alters gut microbiota and mitigates intestinal mucosal injury induced by cyclophosphamide

2017 ◽  
Vol 8 (9) ◽  
pp. 3383-3393 ◽  
Author(s):  
Hongjie Shi ◽  
Yaoguang Chang ◽  
Yuan Gao ◽  
Xiong Wang ◽  
Xin Chen ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Mucosal Injury ◽  
Cancer Drug ◽  
Intestinal Mucosal Injury

Cyclophosphamide (cy) is a widely used cancer drug.

scholarly journals Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Minmin Li ◽  
Chengwen Lu ◽  
Leiming Zhang ◽  
Jianqiao Zhang ◽  
Yuan Du ◽  
...  
Keyword(s):  
Animal Models ◽  
Oral Administration ◽  
Acute Inflammation ◽  
Low Dose ◽  
Cecal Ligation ◽  
Mucosal Injury ◽  
Paw Edema ◽  
Junction Protein ◽  
Intestinal Mucosal Injury ◽  
Cox 2

The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP) induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2) and cyclooxygenase- (COX-) 2. In CLP model, low dose of escin ameliorates endotoxin induced liver injury and intestinal mucosal injury and increases the expression of tight junction protein claudin-5 in mice. These findings suggest that escin effectively inhibits acute inflammation and reduces intestinal mucosal injury in animal models.

scholarly journals Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer

2020 ◽  
Vol 21 (2) ◽  
pp. 386 ◽  
Author(s):  
Ching-Wei Chang ◽  
Hung-Chang Lee ◽  
Li-Hui Li ◽  
Jen-Shiu Chiang Chiau ◽  
Tsang-En Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Common Adverse Effect ◽  
Mucosal Injury ◽  
Fecal Microbiota ◽  
Intestinal Injury ◽  
Toll Like Receptors ◽  
Adenocarcinoma Cells ◽  
Intestinal Mucositis

FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin), a 5-fluorouracil (5-FU)-based chemotherapy regimen, is one of most common therapeutic regimens for colorectal cancer. However, intestinal mucositis is a common adverse effect for which no effective preventive strategies exist. Moreover, the efficacy and the safety of fecal microbiota transplants (FMT) in cancer patients treated with anti-neoplastic agents are still scant. We investigated the effect of FMT on FOLFOX-induced mucosal injury. BALB/c mice implanted with syngeneic CT26 colorectal adenocarcinoma cells were orally administered FMT daily during and two days after five-day injection of FOLFOX regimen for seven days. Administration of FOLFOX significantly induced marked levels of diarrhea and intestinal injury. FMT reduced the severity of diarrhea and intestinal mucositis. Additionally, the number of goblet cells and zonula occludens-1 decreased, while apoptotic and NF-κB-positive cells increased following FOLFOX treatment. The expression of toll-like receptors (TLRs), MyD88, and serum IL-6 were upregulated following FOLFOX treatment. These responses were attenuated following FMT. The disrupted fecal gut microbiota composition was also restored by FMT after FOLFOX treatment. Importantly, FMT did not cause bacteremia and safely alleviated FOLFOX-induced intestinal mucositis in colorectal cancer-bearing mice. The putative mechanism may involve the gut microbiota TLR-MyD88-NF-κB signaling pathway in mice with implanted colorectal carcinoma cells.

scholarly journals Small intestinal mucosal injury in patients with gastrointestinal cancer who develop complicated fluoropyrimidine-induced diarrhea

2020 ◽  
Author(s):  
Miho Sakumura ◽  
Takayuki Ando ◽  
Ayumu Hosokawa ◽  
Iori Motoo ◽  
Hiroshi Mihara ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Gastrointestinal Cancer ◽  
Mucosal Injury ◽  
Mucosal Damage ◽  
Common Adverse Event ◽  
Limited Data ◽  
Intestinal Mucosal Injury ◽  
Small Intestinal ◽  
Low Incidence ◽  
American Society

Abstract Background: Diarrhea is a common adverse event of fluoropyrimidine-based chemotherapy. However, no treatment with promising evidence has been established for chemotherapy-induced diarrhea (CID); limited data are available on the frequency of complicated CID and small intestinal mucosal damage. In this current study, we aimed to determine the incidence of complicated CID and mucosal injury among patients with complicated CID receiving fluoropyrimidine via small bowel capsule endoscopy (CE). Methods: In total, 536 patients with advanced or recurrent gastrointestinal cancer who received fluoropyrimidine-based chemotherapy were retrospectively analyzed. Diarrhea was evaluated using the Common Terminology Criteria for Adverse Events version 4. Complicated CID was defined according to the American Society of Clinical Oncology guidelines. To evaluate small intestinal mucosal injury in patients with complicated CID, CE was performed. Multivariate analysis was performed to identify risk factors for complicated CID.Results: In total, 32 (6%) patients developed complicated CID. Complicating symptoms were noted in 24 (75%) patients, with cramping, vomiting, and sepsis being observed in 15 (63%), 8 (33%), and 2 (8%) patients, respectively. Among the 12 patients who underwent CE, 10 (83%) exhibited abnormal findings. Multivariate analysis showed that oral fluoropyrimidine administration was a risk factor for complicated CID (odds ratio, 2.95; 95% confidence interval, 1.06–8.19).Conclusions: Despite the relatively low incidence of complicated CID, most patients with complicated CID exhibited small intestinal mucosal injury, with some developing fever or sepsis as complications. Thus, bacterial translocation secondary to small intestinal mucosal injury should be considered in the management of patients with complicated fluoropyrimidine-induced diarrhea.

Acetyl salicylic acid induces damage to intestinal epithelial cells by oxidation-related modifications of ZO-1

2012 ◽  
Vol 303 (8) ◽  
pp. G927-G936 ◽  
Author(s):  
Akifumi Fukui ◽  
Yuji Naito ◽  
Osamu Handa ◽  
Munehiro Kugai ◽  
Toshifumi Tsuji ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Salicylic Acid ◽  
Mucosal Injury ◽  
Cell Permeability ◽  
Acetyl Salicylic Acid ◽  
Dependent Manner ◽  
Ros Production ◽  
Junction Protein ◽  
Intestinal Mucosal Injury ◽  
Small Intestinal

Acetyl salicylic acid (ASA) is one of the most frequently prescribed medications for the secondary prevention of cardiovascular and cerebrovascular events. It has recently been reported to cause small intestinal mucosal injury at a considerably higher rate than previously believed. The aim of this study is to investigate the mechanism by which this occurs using an in vitro small intestine model focusing on the role of oxidative stress and cell permeability. Differentiated Caco-2 exhibits a phenotype similar to human small intestinal epithelium. We measured whether ASA induced the increase of differentiated Caco-2 permeability, the decrease of tight junction protein expression, the production of reactive oxygen species (ROS), and the expression of ROS-modified zonula occludens-1 (ZO-1) protein. In some experiments, Mn(III) tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP, a superoxide dismutase mimetic) was used. The nontoxic concentration of ASA decreased transepithelial electrical resistance and increased the flux of fluorescein isothiocyanate-conjugated dextran across Caco-2 in a time-dependent manner. The same concentration of ASA significantly decreased ZO-1 expression among TJ proteins as assessed by Western blot and immunocytochemistry and increased ROS production and the expression of oxidative stress-modified ZO-1 protein. However, MnTMPyP suppressed the ASA-induced increased intercellular permeability and the ASA-induced ROS-modified ZO-1 expression. Our findings indicate that ASA-induced ROS production can specifically modify the expression of ZO-1 protein and induce increased cell permeability, which may ultimately cause small intestinal mucosal injury.

scholarly journals Role of Dietary Nutritional Treatment on Hepatic and Intestinal Damage in Transplantation with Steatotic and Non-Steatotic Liver Grafts from Brain Dead Donors

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2554
Author(s):  
Marc Micó-Carnero ◽  
Araní Casillas-Ramírez ◽  
Albert Caballeria-Casals ◽  
Carlos Rojano-Alfonso ◽  
Alfredo Sánchez-González ◽  
...  
Keyword(s):  
Growth Factor ◽  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Mucosal Damage ◽  
Hepatic Damage ◽  
Intestinal Damage ◽  
Edema Formation ◽  
Steatotic Liver ◽  
Damage And Failure

Herein, we investigate whether: (1) the administration of glucose or a lipid emulsion is useful in liver transplantation (LT) using steatotic (induced genetically or nutritionally) or non-steatotic livers from donors after brain death (DBDs); and (2) any such benefits are due to reductions in intestinal damage and consequently to gut microbiota preservation. In recipients from DBDs, we show increased hepatic damage and failure in the maintenance of ATP, glycogen, phospholipid and growth factor (HGF, IGF1 and VEGFA) levels, compared to recipients from non-DBDs. In recipients of non-steatotic grafts from DBDs, the administration of glucose or lipids did not protect against hepatic damage. This was associated with unchanged ATP, glycogen, phospholipid and growth factor levels. However, the administration of lipids in steatotic grafts from DBDs protected against damage and ATP and glycogen drop and increased phospholipid levels. This was associated with increases in growth factors. In all recipients from DBDs, intestinal inflammation and damage (evaluated by LPS, vascular permeability, mucosal damage, TLR4, TNF, IL1, IL-10, MPO, MDA and edema formation) was not shown. In such cases, potential changes in gut microbiota would not be relevant since neither inflammation nor damage was evidenced in the intestine following LT in any of the groups evaluated. In conclusion, lipid treatment is the preferable nutritional support to protect against hepatic damage in steatotic LT from DBDs; the benefits were independent of alterations in the recipient intestine.

scholarly journals Distinct Changes in Gut Microbiota Are Associated with Estradiol-Mediated Protection from Diet-Induced Obesity in Female Mice

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 499
Author(s):  
Kalpana D. Acharya ◽  
Hye L. Noh ◽  
Madeline E. Graham ◽  
Sujin Suk ◽  
Randall H. Friedline ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Glucose Turnover ◽  
Female Mice ◽  
Adult Mice ◽  
Diet Induced Obesity ◽  
Metabolic Dysregulation ◽  
Regulation Of Metabolism ◽  
Junction Protein

A decrease in ovarian estrogens in postmenopausal women increases the risk of weight gain, cardiovascular disease, type 2 diabetes, and chronic inflammation. While it is known that gut microbiota regulates energy homeostasis, it is unclear if gut microbiota is associated with estradiol regulation of metabolism. In this study, we tested if estradiol-mediated protection from high-fat diet (HFD)-induced obesity and metabolic changes are associated with longitudinal alterations in gut microbiota in female mice. Ovariectomized adult mice with vehicle or estradiol (E2) implants were fed chow for two weeks and HFD for four weeks. As reported previously, E2 increased energy expenditure, physical activity, insulin sensitivity, and whole-body glucose turnover. Interestingly, E2 decreased the tight junction protein occludin, suggesting E2 affects gut epithelial integrity. Moreover, E2 increased Akkermansia and decreased Erysipleotrichaceae and Streptococcaceae. Furthermore, Coprobacillus and Lactococcus were positively correlated, while Akkermansia was negatively correlated, with body weight and fat mass. These results suggest that changes in gut epithelial barrier and specific gut microbiota contribute to E2-mediated protection against diet-induced obesity and metabolic dysregulation. These findings provide support for the gut microbiota as a therapeutic target for treating estrogen-dependent metabolic disorders in women.

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