scholarly journals Another One Bites the Gut: Nuclear Receptor LRH-1 in Intestinal Regeneration and Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 896
Author(s):  
Roberta Zerlotin ◽  
Maria Arconzo ◽  
Elena Piccinin ◽  
Antonio Moschetta
Keyword(s):  
Nuclear Receptor ◽  
Intestinal Epithelium ◽  
Inflammatory Cell ◽  
Cellular Proliferation ◽  
Dietary Habits ◽  
Dna Damages ◽  
Proliferation And Differentiation ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Pathological Manifestation

The process of self-renewal in normal intestinal epithelium is characterized by a fine balance between proliferation, differentiation, migration, and cell death. When even one of these aspects escapes the normal control, cellular proliferation and differentiation are impaired, with consequent onset of tumorigenesis. In humans, colorectal cancer (CRC) is the main pathological manifestation of this derangement. Nowadays, CRC is the world’s fourth most deadly cancer with a limited survival after treatment. Several conditions can predispose to CRC development, including dietary habits and pre-existing inflammatory bowel diseases. Given their extraordinary ability to interact with DNA, it is widely known that nuclear receptors play a key role in the regulation of intestinal epithelium, orchestrating the expression of a series of genes involved in developmental and homeostatic pathways. In particular, the nuclear receptor Liver Receptor Homolog-1 (LRH-1), highly expressed in the stem cells localized in the crypts, promotes intestine cell proliferation and renewal in both direct and indirect DNA-binding manner. Furthermore, LRH-1 is extensively correlated with diverse intestinal inflammatory pathways. These evidence shed a light in the dynamic intestinal microenvironment in which increased regenerative epithelial cell turnover, mutagenic insults, and chronic DNA damages triggered by factors within an inflammatory cell-rich microenvironment act synergistically to favor cancer onset and progression.

scholarly journals Loss of Nckx3 Exacerbates Experimental DSS-Induced Colitis in Mice through p53/NF-κB Pathway

2021 ◽  
Vol 22 (5) ◽  
pp. 2645
Author(s):  
Dinh Nam Tran ◽  
Seon Myeong Go ◽  
Seon-Mi Park ◽  
Eui-Man Jung ◽  
Eui-Bae Jeung
Keyword(s):  
Immune Response ◽  
Cellular Proliferation ◽  
Intestinal Inflammation ◽  
Critical Role ◽  
Experimental Colitis ◽  
Innate Immune ◽  
Inflammatory Conditions ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Microarray Analyses

Inflammatory bowel diseases (IBDs) comprises a range of chronic inflammatory conditions of the intestinal tract. The incidence and prevalence of IBDs are increasing worldwide, but the precise etiology of these diseases is not completely understood. Calcium signaling plays a regulatory role in cellular proliferation. Nckx3, a potassium-dependent Na+/Ca2+ exchanger, is not only expressed in the brain but also in the aortic, uterine, and intestinal tissues, which contain abundant smooth muscle cells. This study investigated the role of Nckx3 in intestinal inflammation. Microarray analyses revealed the upregulation of the innate immune response-associated genes in the duodenum of Nckx3 knockout (KO) mice. The Nckx3 KO mice also showed an increase in IBD- and tumorigenesis-related genes. Using dextran sodium sulfate (DSS)-induced experimental colitis mice models, the Nckx3 KO mice showed severe colitis. Furthermore, the pathways involving p53 and NF-κB signaling were significantly upregulated by the absence of Nckx3. Overall, Nckx3 plays a critical role in the innate immune and immune response and may be central to the pathogenesis of IBD.

scholarly journals Intestinal Taxa Abundance and Diversity in Inflammatory Bowel Disease Patients: An Analysis including Covariates and Confounders

Nutrients ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 260
Author(s):  
Adelaide Teofani ◽  
Irene Marafini ◽  
Federica Laudisi ◽  
Daniele Pietrucci ◽  
Silvia Salvatori ◽  
...  
Keyword(s):  
Dairy Products ◽  
Dietary Habits ◽  
Rrna Gene ◽  
Disease Extent ◽  
Intestinal Dysbiosis ◽  
Gene Sequence Analysis ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Abundance And Diversity ◽  
The Impact

Intestinal dysbiosis has been widely documented in inflammatory bowel diseases (IBDs) and is thought to influence the onset and perpetuation of gut inflammation. However, it remains unclear whether such bacterial changes rely in part on the modification of an IBD-associated lifestyle (e.g., smoking and physical activity) and diet (e.g., rich in dairy products, cereals, meat and vegetables). In this study, we investigated the impact of these habits, which we defined as confounders and covariates, on the modulation of intestinal taxa abundance and diversity in IBD patients. 16S rRNA gene sequence analysis was performed using genomic DNA extracted from the faecal samples of 52 patients with Crohn’s disease (CD) and 58 with ulcerative colitis (UC), which are the two main types of IBD, as well as 42 healthy controls (HC). A reduced microbial diversity was documented in the IBD patients compared with the HC. Moreover, we identified specific confounders and covariates that influenced the association between some bacterial taxa and disease extent (in UC patients) or behaviour (in CD patients) compared with the HC. In particular, a PERMANOVA stepwise regression identified the variables “age”, “eat yogurt at least four days per week” and “eat dairy products at least 4 days per week” as covariates when comparing the HC and patients affected by ulcerative proctitis (E1), left-sided UC (distal UC) (E2) and extensive UC (pancolitis) (E3). Instead, the variables “age”, “gender”, “eat meat at least four days per week” and “eat bread at least 4 days per week” were considered as covariates when comparing the HC with the CD patients affected by non-stricturing, non-penetrating (B1), stricturing (B2) and penetrating (B3) diseases. Considering such variables, our analysis indicated that the UC extent differentially modulated the abundance of the Bifidobacteriaceae, Rikenellaceae, Christensenellaceae, Marinifilaceae, Desulfovibrionaceae, Lactobacillaceae, Streptococcaceae and Peptostreptococcaceae families, while the CD behaviour influenced the abundance of Christensenellaceae, Marinifilaceae, Rikenellaceae, Ruminococcaceae, Barnesiellaceae and Coriobacteriaceae families. In conclusion, our study indicated that some covariates and confounders related to an IBD-associated lifestyle and dietary habits influenced the intestinal taxa diversity and relative abundance in the CD and UC patients compared with the HC. Indeed, such variables should be identified and excluded from the analysis to characterize the bacterial families whose abundance is directly modulated by IBD status, as well as disease extent or behaviour.

scholarly journals Resolution of Inflammation and Gut Repair in IBD: Translational Steps Towards Complete Mucosal Healing

2020 ◽  
Vol 26 (8) ◽  
pp. 1131-1143 ◽  
Author(s):  
Gwo-tzer Ho ◽  
Jennifer A Cartwright ◽  
Emily J Thompson ◽  
Calum C Bain ◽  
Adriano G Rossi
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Inflammatory Cell ◽  
Mucosal Healing ◽  
Treatment Target ◽  
Resolution Of Inflammation ◽  
Epithelial Repair ◽  
New Knowledge ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Macrophage Populations

Abstract Despite significant recent therapeutic advances, complete mucosal healing remains a difficult treatment target for many patients with inflammatory bowel diseases (IBD) to achieve. Our review focuses on the translational concept of promoting resolution of inflammation and repair as a necessary adjunctive step to reach this goal. We explore the roles of inflammatory cell apoptosis and efferocytosis to promote resolution, the new knowledge of gut monocyte-macrophage populations and their secreted prorepair mediators, and the processes of gut epithelial repair and regeneration to bridge this gap. We discuss the need and rationale for this vision and the tangible steps toward integrating proresolution therapies in IBD.

scholarly journals P034 Human primary 2D culture as a tool to explore JAK1 pathway inhibition in the intestinal epithelium using siRNA technology

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S147-S148
Author(s):  
I Dotti ◽  
E Sulpice ◽  
A Nougarède ◽  
D Jary ◽  
F Clément ◽  
...  
Keyword(s):  
Intestinal Epithelium ◽  
Target Genes ◽  
Local Therapy ◽  
The Novel ◽  
Sirna Transfection ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Pathway Inhibition ◽  
Human Intestinal Epithelium ◽  
Dependent Pathway

Abstract Background Oral inhibitors of JAK1 have become promising therapeutic agents for the treatment of inflammatory bowel diseases (IBD); however, concerns have been raised regarding their specificity and safety profiles. Currently, a local therapy based on specific JAK1 siRNA combined with lipid nanoparticle (LNP) technology is under investigation as a safer alternative to JAK inhibitors.The purpose of this study is to explore the inhibition of the JAK1 pathway in the intestinal epithelium mediated by siRNA/LNP technology, using human primary 2D culture. Methods Human primary 2D cultures were generated from colonic 3D organoids of non-IBD donors. The efficiency of JAK1 pathway inhibition was tested in IFN-y stimulated cultures using either filgotinib (a JAK1 inhibitor, used as a control) or the novel human JAK1 siRNA. JAK1 siRNA transfection was performed using Lipofectamine or LNPs. qPCR was performed on a panel of JAK1 target genes to evaluate the efficiency of JAK1 pathway inhibition. Results Incubation of the 2D culture with IFN-y induced the activation of the JAK1 pathway, as suggested by the significant up-regulation of JAK1-dependent genes (i.e., CXCL10, SOCS1, SOCS3 and PLA2G2A). The addition of filgotinib to the culture efficiently inhibited the JAK1 pathway by suppressing the expression of JAK1-target genes. JAK1 siRNA transfection using Lipofectamine reduced JAK1 mRNA expression by 50%, which was mirrored by the concomitant down-regulation (between 60 and 80%) of JAK1-dependent genes. Importantly, the silencing efficiency of the JAK1-dependent pathway by LNPs was comparable to that observed using Lipofectamine. Conclusion Organoid-derived 2D culture is a useful model for investigating the activation of the JAK1 pathway and its pharmacological inhibition in human intestinal epithelium. In particular, siRNA/LNP nanoplexes may be a promising technology for locally delivering highly specific siRNAs to the intestinal mucosa, which could pave the way for the development of more effective treatments for IBD patients.

scholarly journals Prospects for application of physical exercises and phytotherapy in patients with ulcerative colitis

2020 ◽  
pp. 22-24
Author(s):  
V. A. Akhmedov ◽  
T. I. Melikov
Keyword(s):  
Ulcerative Colitis ◽  
Physical Inactivity ◽  
Dietary Habits ◽  
Developed Countries ◽  
Physical Exercises ◽  
The World ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
The Developed Countries ◽  
Methods Of Treatment

The incidence and prevalence of inflammatory bowel diseases rapidly increased in last years in developed countries and the rise witnessed in the rest of the world closely correlates with adopting a western lifestyle. These observations support the notion that a variety of environmental factors contribute to the pathogenesis of intestinal diseases. In the developed countries, peoples’ lifestyle has changed significantly, being affected by serious modifications in dietary habits and physical inactivity. Those changes in lifestyle may have a bearing on the course of the disease and require correction with the use of physical exercises and other non-drug methods of treatment.

scholarly journals Calprotectin: from biomarker to biological function

Gut ◽  
2021 ◽  
pp. gutjnl-2021-324855
Author(s):  
Almina Jukic ◽  
Latifa Bakiri ◽  
Erwin F. Wagner ◽  
Herbert Tilg ◽  
Timon E. Adolph
Keyword(s):  
Dietary Habits ◽  
Biological Function ◽  
Inflammatory Diseases ◽  
Mucosal Inflammation ◽  
Non Invasive ◽  
Mucosal Surfaces ◽  
Organ Systems ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Substantial Morbidity

The incidence of inflammatory bowel diseases (IBD) emerged with Westernisation of dietary habits worldwide. Crohn’s disease and ulcerative colitis are chronic debilitating conditions that afflict individuals with substantial morbidity and challenge healthcare systems across the globe. Since identification and characterisation of calprotectin (CP) in the 1980s, faecal CP emerged as significantly validated, non-invasive biomarker that allows evaluation of gut inflammation. Faecal CP discriminates between inflammatory and non-inflammatory diseases of the gut and portraits the disease course of human IBD. Recent studies revealed insights into biological functions of the CP subunits S100A8 and S100A9 during orchestration of an inflammatory response at mucosal surfaces across organ systems. In this review, we summarise longitudinal evidence for the evolution of CP from biomarker to rheostat of mucosal inflammation and suggest an algorithm for the interpretation of faecal CP in daily clinical practice. We propose that mechanistic insights into the biological function of CP in the gut and beyond may facilitate interpretation of current assays and guide patient-tailored medical therapy in IBD, a concept warranting controlled clinical trials.

scholarly journals Extracellular Matrix Mechanical Properties and Regulation of the Intestinal Stem Cells: When Mechanics Control Fate

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2629
Author(s):  
Lauriane Onfroy-Roy ◽  
Dimitri Hamel ◽  
Julie Foncy ◽  
Laurent Malaquin ◽  
Audrey Ferrand
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Intestinal Barrier ◽  
Intestinal Stem Cells ◽  
Cellular Events ◽  
Proliferation And Differentiation ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Intestinal Barrier Integrity

Intestinal stem cells (ISC) are crucial players in colon epithelium physiology. The accurate control of their auto-renewal, proliferation and differentiation capacities provides a constant flow of regeneration, maintaining the epithelial intestinal barrier integrity. Under stress conditions, colon epithelium homeostasis in disrupted, evolving towards pathologies such as inflammatory bowel diseases or colorectal cancer. A specific environment, namely the ISC niche constituted by the surrounding mesenchymal stem cells, the factors they secrete and the extracellular matrix (ECM), tightly controls ISC homeostasis. Colon ECM exerts physical constraint on the enclosed stem cells through peculiar topography, stiffness and deformability. However, little is known on the molecular and cellular events involved in ECM regulation of the ISC phenotype and fate. To address this question, combining accurately reproduced colon ECM mechanical parameters to primary ISC cultures such as organoids is an appropriated approach. Here, we review colon ECM physical properties at physiological and pathological states and their bioengineered in vitro reproduction applications to ISC studies.

scholarly journals Lactobacillus Paracasei R3 Protects Against Dextran Sulfate Sodium (DSS)-Induced Colitis in Mice via Regulating Th17/Treg Cell Balance

2021 ◽  
Author(s):  
Juan Huang ◽  
Ziyan Yang ◽  
Yanyun Li ◽  
Xingxing Chai ◽  
Yanfang Liang ◽  
...  
Keyword(s):  
Inflammatory Cell ◽  
Lactobacillus Paracasei ◽  
Intestinal Microbiome ◽  
Host Responses ◽  
Murine Colitis ◽  
Treg Function ◽  
Bowel Diseases ◽  
Infant Feces ◽  
Inflammatory Bowel ◽  
Cell Balance

Abstract Inflammatory bowel diseases (IBD), mainly comprising ulcerative colitis (UC) and Crohn's Disease, are most often a polygenic disorder with contributions from the intestinal microbiome, defects in barrier function, and dysregulated host responses to microbial stimulation. Strategies that target the microbiota have emerged as potential therapies and, of these, probiotics have gained the greatest attention. Herein, we isolated a strain of Lactobacillus paracasei R3 (L.p R3) with strong biofilm formation ability from infant feces. Interestingly, we also found L.p R3 strain can ameliorate the general symptoms of murine colitis, alleviate inflammatory cell infiltration and inhibit Th17 while promote Treg function in murine DSS-induced colitis. Overall, this study suggested that L.p R3 strain significantly improves the symptoms and the pathological damage of mice with colitis and influences the immune function by regulating Th17/Treg cell balance in DSS-induced colitis in mice.

Sign in / Sign up

Export Citation Format

Share Document