scholarly journals Gut Dysbiosis and Intestinal Barrier Dysfunction: Potential Explanation for Early-Onset Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Siti Maryam Ahmad Kendong ◽  
Raja Affendi Raja Ali ◽  
Khairul Najmi Muhammad Nawawi ◽  
Hajar Fauzan Ahmad ◽  
Norfilza Mohd Mokhtar
Keyword(s):  
Colorectal Cancer ◽  
Environmental Factors ◽  
Gut Microbiota ◽  
Early Onset ◽  
Early Stage ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Gut Dysbiosis ◽  
Early Onset Colorectal Cancer

Colorectal cancer (CRC) is a heterogeneous disease that commonly affects individuals aged more than 50 years old globally. Regular colorectal screening, which is recommended for individuals aged 50 and above, has decreased the number of cancer death toll over the years. However, CRC incidence has increased among younger population (below 50 years old). Environmental factors, such as smoking, dietary factor, urbanization, sedentary lifestyle, and obesity, may contribute to the rising trend of early-onset colorectal cancer (EOCRC) because of the lack of genetic susceptibility. Research has focused on the role of gut microbiota and its interaction with epithelial barrier genes in sporadic CRC. Population with increased consumption of grain and vegetables showed high abundance of Prevotella, which reduces the risk of CRC. Microbes, such as Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli deteriorate in the intestinal barrier, which leads to the infiltration of inflammatory mediators and chemokines. Gut dysbiosis may also occur following inflammation as clearly observed in animal model. Both gut dysbiosis pre- or post-inflammatory process may cause major alteration in the morphology and functional properties of the gut tissue and explain the pathological outcome of EOCRC. The precise mechanism of disease progression from an early stage until cancer establishment is not fully understood. We hypothesized that gut dysbiosis, which may be influenced by environmental factors, may induce changes in the genome, metabolome, and immunome that could destruct the intestinal barrier function. Also, the possible underlying inflammation may give impact microbial community leading to disruption of physical and functional role of intestinal barrier. This review explains the potential role of the interaction among host factors, gut microenvironment, and gut microbiota, which may provide an answer to EOCRC.

scholarly journals The DNA Sensor AIM2 Protects against Streptozotocin-Induced Type 1 Diabetes by Regulating Intestinal Homeostasis via the IL-18 Pathway

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 959 ◽  
Author(s):  
Jefferson Antônio Leite ◽  
Gabriela Pessenda ◽  
Isabel C. Guerra-Gomes ◽  
Alynne Karen Mendonça de Santana ◽  
Camila André Pereira ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Gut Microbiota ◽  
Bacterial Translocation ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Dna Sensor ◽  
Proinflammatory Response

Pattern recognition receptors (PRRs), such as Nod2, Nlrp3, Tlr2, Trl4, and Tlr9, are directly involved in type 1 diabetes (T1D) susceptibility. However, the role of the cytosolic DNA sensor, AIM2, in T1D pathogenesis is still unknown. Here, we demonstrate that C57BL/6 mice lacking AIM2 (AIM2−/−) are prone to streptozotocin (STZ)-induced T1D, compared to WT C57BL/6 mice. The AIM2−/− mice phenotype is associated with a greater proinflammatory response in pancreatic tissues, alterations in gut microbiota and bacterial translocation to pancreatic lymph nodes (PLNs). These alterations are related to an increased intestinal permeability mediated by tight-junction disruption. Notably, AIM2−/− mice treated with broad-spectrum antibiotics (ABX) are protected from STZ-induced T1D and display a lower pancreatic proinflammatory response. Mechanistically, the AIM2 inflammasome is activated in vivo, leading to an IL-18 release in the ileum at 15 days after an STZ injection. IL-18 favors RegIIIγ production, thus mitigating gut microbiota alterations and reinforcing the intestinal barrier function. Together, our findings show a regulatory role of AIM2, mediated by IL-18, in shaping gut microbiota and reducing bacterial translocation and proinflammatory response against insulin-producing β cells, which ultimately results in protection against T1D onset in an STZ-induced diabetes model.

scholarly journals Role of rare variants in undetermined multiple adenomatous polyposis and early-onset colorectal cancer

2012 ◽  
Vol 57 (11) ◽  
pp. 709-716 ◽  
Author(s):  
Jérémie H Lefevre ◽  
Carolina Bonilla ◽  
Chrystelle Colas ◽  
Bruce Winney ◽  
Elaine Johnstone ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Early Onset ◽  
Rare Variants ◽  
Adenomatous Polyposis ◽  
Early Onset Colorectal Cancer

scholarly journals The Role of Gut Microbiota in Intestinal Inflammation with Respect to Diet and Extrinsic Stressors

2019 ◽  
Vol 7 (8) ◽  
pp. 271 ◽  
Author(s):  
Stefani Lobionda ◽  
Panida Sittipo ◽  
Hyog Young Kwon ◽  
Yun Kyung Lee
Keyword(s):  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Environmental Stressors ◽  
Intestinal Barrier Function ◽  
Symbiotic Relationship ◽  
Inflammatory Bowel ◽  
Host Metabolism ◽  
The Relationship

The gut microbiota maintains a symbiotic relationship with the host and regulates several important functions including host metabolism, immunity, and intestinal barrier function. Intestinal inflammation and inflammatory bowel disease (IBD) are commonly associated with dysbiosis of the gut microbiota. Alterations in the gut microbiota and associated changes in metabolites as well as disruptions in the intestinal barrier are evidence of the relationship between the gut microbiota and intestinal inflammation. Recent studies have found that many factors may alter the gut microbiota, with the effects of diet being commonly-studied. Extrinsic stressors, including environmental stressors, antibiotic exposure, sleep disturbance, physical activity, and psychological stress, may also play important roles in altering the composition of the gut microbiota. Herein, we discuss the roles of the gut microbiota in intestinal inflammation in relation to diet and other extrinsic stressors.

scholarly journals The Role of Gut Dysbiosis in the Bone–Vascular Axis in Chronic Kidney Disease

Toxins ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 285 ◽  
Author(s):  
Pieter Evenepoel ◽  
Sander Dejongh ◽  
Kristin Verbeke ◽  
Bjorn Meijers
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Mineral Density ◽  
Bone Mineral Density Loss ◽  
Gut Dysbiosis ◽  
Increased Risk ◽  
Fermentation Pattern

Patients with chronic kidney disease (CKD) are at increased risk of bone mineral density loss and vascular calcification. Bone demineralization and vascular mineralization often concur in CKD, similar to what observed in the general population. This contradictory association is commonly referred to as the ‘calcification paradox’ or the bone–vascular axis. Mounting evidence indicates that CKD-associated gut dysbiosis may be involved in the pathogenesis of the bone–vascular axis. A disrupted intestinal barrier function, a metabolic shift from a predominant saccharolytic to a proteolytic fermentation pattern, and a decreased generation of vitamin K may, alone or in concert, drive a vascular and skeletal pathobiology in CKD patients. A better understanding of the role of gut dysbiosis in the bone–vascular axis may open avenues for novel therapeutics, including nutriceuticals.

scholarly journals Bile acid supplementation improves murine pancreatitis in association with the gut microbiota

2020 ◽  
Author(s):  
You-Dong Wan ◽  
Rui-Xue Zhu ◽  
Xin-Ting Pan
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Pancreatic Injury ◽  
Farnesoid X Receptor ◽  
Intestinal Barrier Function ◽  
Signaling Receptors

ABSTRACTDisorders of bile acids (BAs) are closely related to the development of liver and intestinal diseases, including acute pancreatitis (AP). However, the mechanism underlying the involvement of BAs in AP development remains unclear. We used intraperitoneal injection of cerulein to construct AP mouse models. These mice had significantly reduced tauroursodeoxycholic acid (TUDCA) and an imbalance of intestinal microbiota, based on 16S rDNA gene sequencing. To explore the role of AP-induced intestinal microbiota changes in the development of AP, we transplanted stool obtained from AP mice to antibiotic-treated, microbiota-depleted healthy mice. Microbiota-depleted mice presented injury to the intestinal barrier function and pancreas. Additionally, microbiota depletion reduced AP-associated pancreatic injury. This indicated that the gut microbiota may worsen AP. As TUDCA was deficient in AP mice, we gavaged AP mice with it, and evaluated subsequent expression changes in the bile acid signaling receptors farnesoid-x-receptor (FXR) and its target gene fibroblast growth factor (FGF) 15. These were downregulated, and pancreatic and intestinal barrier function injury were mitigated. Similar results were found in microbiota-depleted AP without BA treatment. However, we did not observe further downregulation of the FXR signaling pathway in microbiota-depleted AP mice given TUDCA, indicating that improvement of pancreatitis by TUDCA may be associated with gut microbiota. Our analysis of changes to the gut microbiota in AP indicated that Lactobacilli may be the key contributors. Taken together, our study shows that supplementation with BAs could improve bile acid-FXR-FGF15 signaling, and reduce pancreatic and intestinal injury, and that this effect may be associated with the gut microbiota.

scholarly journals Gut Microbiota Profiles in Early- and Late-Onset Colorectal Cancer: A Potential Diagnostic Biomarker in the Future

Digestion ◽  
2021 ◽  
pp. 1-10
Author(s):  
Murdani Abdullah ◽  
Ninik Sukartini ◽  
Saskia Aziza Nursyirwan ◽  
Rabbinu Rangga Pribadi ◽  
Hasan Maulahela ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Gut Microbiota ◽  
Late Onset ◽  
Diagnostic Biomarker ◽  
Incidence And Mortality ◽  
The Future ◽  
Early Onset Colorectal Cancer ◽  
Gut Microbiota Dysbiosis

<b><i>Background:</i></b> Researchers believe the role of gut microbiota dysbiosis in the raised incidence of early-onset colorectal cancer (EOCRC). The development of EOCRC may be associated with microbiota dysbiosis either dependently or independently (combined with other risk factors). <b><i>Summary:</i></b> Recently, the rising of incidence and mortality of EOCRC have been noted. Some researchers are looking for risk factors influencing this fact. They hypothesize that it may be because of microbiota dysbiosis. Microbiota dysbiosis has been known to promote cancer development through immunity dysregulation and chronic inflammation. Microbiomes profile in late-onset colorectal cancer (LOCRC) among older patients has been documented, but there is still lack of data about microbial profiles among younger colorectal cancer (CRC) patients. This review tries to explain microbial profiles differences between EOCRC and LOCRC as a potential diagnostic biomarker in the future, and whether microbiota can have a role in EOCRC genesis. <b><i>Key Messages:</i></b> Microbiota does vary with age, and EOCRC may be associated with colonization of some specific bacteria. Further studies about gut microbiota profiles in EOCRC and LOCRC may provide a new insight on diagnostic biomarker of CRC.

scholarly journals The Role of Diet and Lifestyle in Early-Onset Colorectal Cancer: A Systematic Review

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5933
Author(s):  
Marta Puzzono ◽  
Alessandro Mannucci ◽  
Simone Grannò ◽  
Raffaella Alessia Zuppardo ◽  
Andrea Galli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factors ◽  
Systematic Review ◽  
Young Adults ◽  
Early Onset ◽  
Current Evidence ◽  
Exogenous Factors ◽  
Diet And Lifestyle ◽  
Early Onset Colorectal Cancer

The incidence of early-onset colorectal cancer, defined as colorectal cancer occurring in young adults under the age of 50, is increasing globally. Knowledge of the etiological factors in young adults is far from complete. Questionable eoCRCs’ exogenous factors are represented by processed meat, sugary drinks, alcohol, Western dietary pattern, overweight and obesity, physical inactivity, and smoking, though with heterogeneous results. Therefore, we performed a systematic review to summarize the current evidence on the role of diet and lifestyle as eoCRC risk factors. We systematically searched PubMed, Scopus, and EMBASE up to July 2021, for original studies evaluating diet, alcohol, physical activity, BMI, and smoking in eoCRC and included twenty-six studies. Indeed, the exogenous factors could represent modifiable key factors, whose recognition could establish areas of future interventions through public health strategies for eoCRC primary prevention. Additionally, we discussed the role of additional non-modifiable risk factors, and of epigenetic regulation and microbiota as mediators of the eoCRC triggered by diet and lifestyle.

scholarly journals Prenatal Maternal Stress Exacerbates Experimental Colitis of Offspring in Adulthood

2021 ◽  
Vol 12 ◽  
Author(s):  
Yue Sun ◽  
Runxiang Xie ◽  
Lu Li ◽  
Ge Jin ◽  
Bingqian Zhou ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Barrier Function ◽  
Maternal Stress ◽  
Intestinal Barrier ◽  
Experimental Colitis ◽  
Intestinal Barrier Function ◽  
Low Grade ◽  
Prenatal Maternal Stress ◽  
Gut Dysbiosis ◽  
Mucosal Barrier Function

The prevalence of inflammatory bowel disease (IBD) is increasing worldwide and correlates with dysregulated immune response because of gut microbiota dysbiosis. Some adverse early life events influence the establishment of the gut microbiota and act as risk factors for IBD. Prenatal maternal stress (PNMS) induces gut dysbiosis and perturbs the neuroimmune network of offspring. In this study, we aimed to investigate whether PNMS increases the susceptibility of offspring to colitis in adulthood. The related index was assessed during the weaning period and adulthood. We found that PNMS impaired the intestinal epithelial cell proliferation, goblet cell and Paneth cell differentiation, and mucosal barrier function in 3-week-old offspring. PNMS induced low-grade intestinal inflammation, but no signs of microscopic inflammatory changes were observed. Although there was no pronounced difference between the PNMS and control offspring in terms of their overall measures of alpha diversity for the gut microbiota, distinct microbial community changes characterized by increases in Desulfovibrio, Streptococcus, and Enterococcus and decreases in Bifidobacterium and Blautia were induced in the 3-week-old PNMS offspring. Notably, the overgrowth of Desulfovibrio persisted from the weaning period to adulthood, consistent with the results observed using fluorescence in situ hybridization in the colon mucosa. Mechanistically, the fecal microbiota transplantation experiment showed that the gut microbiota from the PNMS group impaired the intestinal barrier function and induced low-grade inflammation. The fecal bacterial solution from the PNMS group was more potent than that from the control group in inducing inflammation and gut barrier disruption in CaCo-2 cells. After treatment with a TNF-α inhibitor (adalimumab), no statistical difference in the indicators of inflammation and intestinal barrier function was observed between the two groups. Finally, exposure to PNMS remarkably increased the values of the histopathological parameters and the inflammatory cytokine production in a mouse model of experimental colitis in adulthood. These findings suggest that PNMS can inhibit intestinal development, impair the barrier function, and cause gut dysbiosis characterized by the persistent overgrowth of Desulfovibrio in the offspring, resulting in exacerbated experimental colitis in adulthood.

Sign in / Sign up

Export Citation Format

Share Document