The α-D-glucan from marine fungus Phoma herbarum YS4108 ameliorated mice colitis by repairing mucosal barrier and maintaining intestinal homeostasis

2020 ◽  
Vol 149 ◽  
pp. 1180-1188
Author(s):  
Wei Liu ◽  
Shuai Tang ◽  
Qianqian Zhao ◽  
Wanyue Zhang ◽  
Kaidong Li ◽  
...  
Keyword(s):  
Marine Fungus ◽  
Mucosal Barrier ◽  
Intestinal Homeostasis ◽  
Phoma Herbarum

Impact of nanomaterials on intestinal mucosal barrier and its application in treating intestinal diseases

2021 ◽  
Author(s):  
Wenshuai Hao ◽  
Ruitao Cha ◽  
Mingzheng Wang ◽  
Pai Zhang ◽  
Xingyu Jiang
Keyword(s):  
The Body ◽  
Mucosal Barrier ◽  
Intestinal Homeostasis ◽  
Intestinal Mucosal Barrier ◽  
Intestinal Diseases ◽  
Harmful Substances

The intestinal mucosal barrier (IMB) is one of the important barriers to prevent harmful substances and pathogens from entering the body environment and maintain intestinal homeostasis. The dysfunction of IMB...

scholarly journals Gut microbiota-derived inosine from dietary barley leaf supplementation attenuates colitis through PPARγ signaling activation

Microbiome ◽  
2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Daotong Li ◽  
Yu Feng ◽  
Meiling Tian ◽  
Junfu Ji ◽  
Xiaosong Hu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Mucosal Barrier ◽  
Chronic Inflammatory Bowel Disease ◽  
Rrna Gene ◽  
Intestinal Homeostasis ◽  
Potential Health ◽  
Barrier Functions ◽  
Barley Leaf ◽  
Purine Metabolite ◽  
Gut Microbiota Dysbiosis

Abstract Background Ulcerative colitis is a type of chronic inflammatory bowel disease closely associated with gut microbiota dysbiosis and intestinal homeostasis dysregulation. Barley leaf (BL) has a long history of use in Traditional Chinese Medicine with potential health-promoting effects on intestinal functions. However, its mechanism of action is not yet clear. Here, we explore the potential modulating roles of gut microbial metabolites of BL to protect against colitis and elucidate the underlying molecular mechanisms. Results Using 16S rRNA gene-based microbiota analysis, we first found that dietary supplementation of BL ameliorated dextran sulfate sodium (DSS)-induced gut microbiota dysbiosis. The mechanisms by which BL protected against DSS-induced colitis were resulted from improved intestinal mucosal barrier functions via the activation of peroxisome proliferator-activated receptor (PPAR)γ signaling. In addition, metabolomic profiling analysis showed that the gut microbiota modulated BL-induced metabolic reprograming in the colonic tissues particularly by the enhancement of glycolysis process. Notably, dietary BL supplementation resulted in the enrichment of microbiota-derived purine metabolite inosine, which could activate PPARγ signaling in human colon epithelial cells. Furthermore, exogenous treatment of inosine reproduced similar protective effects as BL to protect against DSS-induced colitis through improving adenosine 2A receptor (A2AR)/PPARγ-dependent mucosal barrier functions. Conclusions Overall, our findings suggest that the gut microbiota-inosine-A2AR/PPARγ axis plays an important role in the maintenance of intestinal homeostasis, which may represent a novel approach for colitis prevention via manipulation of the gut microbial purine metabolite.

MALAT1 maintains the intestinal mucosal homeostasis in Crohn’s disease via the miR-146b-5p-CLDN11/NUMB pathway

2021 ◽  
Author(s):  
Ying Li ◽  
Liguo Zhu ◽  
Peng Chen ◽  
Ying Wang ◽  
Guang Yang ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Knockout Mice ◽  
Experimental Colitis ◽  
Vital Role ◽  
Mucosal Barrier ◽  
Luciferase Reporter ◽  
Intestinal Homeostasis ◽  
Mucosal Homeostasis ◽  
Novel Target

Abstract Background & Aims Intestinal homeostasis disorder is critical for developing Crohn's disease (CD). Maintaining mucosal barrier integrity is essential for intestinal homeostasis, preventing intestinal injury and complications. Among the remarkably altered long non-coding RNAs (lncRNAs) in CD, we aimed to investigate whether metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) modulated CD and consequent disruption of intestinal homeostasis. Methods Microarray analyses on intestinal mucosa of CD patients and controls were performed to identify dysregulated lncRNAs. MALAT1 expression was investigated via qRT-PCR and its distribution in intestinal tissues was detected using BaseScope. Intestines from MALAT1 knockout mice with colitis were investigated using histological, molecular and biochemical approaches. Effects of intestinal epithelial cells transfected with MALAT1 lentiviruses and Smart Silencer, on monolayer permeability and apical junction complex (AJC) proteins were analysed. MiR-146b-5p were confirmed as a critical MALAT1 mediator in cells transfected with miR-146b-5p mimic/inhibitor and in colitis mice administered with agomir-146b-5p/antagomir-146b-5p. Interaction between MALAT1 and miR-146b-5p was predicted via bioinformatics and validated using Dual-luciferase reporter assay and Ago2-RIP. Results MALAT1 was aberrantly downregulated in the intestine mucosa of CD patients and mice with experimental colitis. MALAT1 knockout mice were hypersensitive to DSS-induced experimental colitis. MALAT1 regulated intestinal mucosal barrier and regained intestinal homeostasis by sequestering miR-146b-5p and maintaining the expression of the AJC proteins NUMB and CLDN11. Conclusions Downregulation of MALAT1 contributed to the pathogenesis of CD by disrupting AJC. Thus, a specific MALAT1-miR-146b-5p-NUMB/CLDN11 pathway that plays a vital role in maintaining intestinal mucosal homeostasis may serve as a novel target for CD treatment.

scholarly journals NSAIDs disrupt intestinal homeostasis by suppressing macroautophagy in intestinal epithelial cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ana M. Chamoun-Emanuelli ◽  
Laura K. Bryan ◽  
Noah D. Cohen ◽  
Taylor L. Tetrault ◽  
Joseph A. Szule ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Clinical Manifestations ◽  
Building Blocks ◽  
Mucosal Barrier ◽  
High Morbidity ◽  
Intestinal Damage ◽  
Intestinal Epithelial ◽  
Intestinal Homeostasis

Abstract Small intestinal damage induced by nonsteroidal anti-inflammatory drugs (NSAIDs) remains an under-recognized clinical disorder. The incomplete understanding of the pathophysiology has hampered the development of prevention and treatment strategies leading to the high morbidity and mortality rates. NSAIDs are known to modulate macroautophagy, a process indispensable for intestinal homeostasis. Whether NSAIDs stimulate or repress macroautophagy and how this correlates with the clinical manifestations of NSAID enteropathy, however, remains unknown. The objectives of this study were to determine whether NSAIDs impaired macroautophagy and how this affects macroautophagy-regulated intestinal epithelial cell (IEC) processes essential for intestinal homeostasis (i.e., clearance of invading pathogens, secretion and composition of mucus building blocks, and inflammatory response). We show that NSAID treatment of IECs inhibits macroautophagy in vitro and in vivo. This inhibition was likely attributed to a reduction in the area and/or distribution of lysosomes available for degradation of macroautophagy-targeted cargo. Importantly, IEC regulatory processes necessary for intestinal homeostasis and dependent on macroautophagy were dysfunctional in the presence of NSAIDs. Since macroautophagy is essential for gastrointestinal health, NSAID-induced inhibition of macroautophagy might contribute to the severity of intestinal injury by compromising the integrity of the mucosal barrier, preventing the clearance of invading microbes, and exacerbating the inflammatory response.

scholarly journals Creatine maintains intestinal homeostasis and protects against colitis

2017 ◽  
Vol 114 (7) ◽  
pp. E1273-E1281 ◽  
Author(s):  
Emre Turer ◽  
William McAlpine ◽  
Kuan-wen Wang ◽  
Tianshi Lu ◽  
Xiaohong Li ◽  
...  
Keyword(s):  
Immune Cell ◽  
Mammalian Target Of Rapamycin ◽  
Metabolic Stress ◽  
Recessive Model ◽  
Mucosal Barrier ◽  
Strongly Correlated ◽  
Intestinal Homeostasis ◽  
Rate Limiting Step ◽  
Phosphocreatine Shuttle

Creatine, a nitrogenous organic acid, replenishes cytoplasmic ATP at the expense of mitochondrial ATP via the phosphocreatine shuttle. Creatine levels are maintained by diet and endogenous synthesis from arginine and glycine. Glycine amidinotransferase (GATM) catalyzes the rate-limiting step of creatine biosynthesis: the transfer of an amidino group from arginine to glycine to form ornithine and guanidinoacetate. We screened 36,530 third-generation germline mutant mice derived from N-ethyl-N-nitrosourea–mutagenized grandsires for intestinal homeostasis abnormalities after oral administration of dextran sodium sulfate (DSS). Among 27 colitis susceptibility phenotypes identified and mapped, one was strongly correlated with a missense mutation in Gatm in a recessive model of inheritance, and causation was confirmed by CRISPR/Cas9 gene targeting. Supplementation of homozygous Gatm mutants with exogenous creatine ameliorated the colitis phenotype. CRISPR/Cas9-targeted (Gatmc/c) mice displayed a normal peripheral immune response and immune cell homeostasis. However, the intestinal epithelium of the Gatmc/c mice displayed increased cell death and decreased proliferation during DSS treatment. In addition, Gatmc/c colonocytes showed increased metabolic stress in response to DSS with higher levels of phospho-AMPK and lower levels of phosphorylation of mammalian target of rapamycin (phospho-mTOR). These findings establish an in vivo requirement for rapid replenishment of cytoplasmic ATP within colonic epithelial cells in the maintenance of the mucosal barrier after injury.

Contribution of the Microbiota to Intestinal Homeostasis and its Role in the Pathogenesis of HIV-1 Infection

2019 ◽  
Vol 17 (1) ◽  
pp. 13-25 ◽  
Author(s):  
Jorge A. Luján ◽  
Maria T. Rugeles ◽  
Natalia A. Taborda
Keyword(s):  
Gut Microbiota ◽  
Hiv Infection ◽  
Circulatory System ◽  
Critical Factor ◽  
Cell Permeability ◽  
Intestinal Lumen ◽  
Mucosal Barrier ◽  
Intestinal Homeostasis ◽  
Integral Role ◽  
And Function

During HIV infection, massive destruction of CD4+ T cells ensues, preferentially depleting the Th17 subset at the gut-associated lymphoid tissue (GALT), leading to a loss of mucosal integrity and an increase in cell permeability. This process favors microbial translocation between the intestinal lumen and the circulatory system, contributing to persistent immune activation and chronic inflammation characteristic of HIV infection. Thus, the gut microbiota plays an integral role in maintaining the structure and function of the mucosal barrier, a critical factor for immune homeostasis. However, in the context of HIV infection, changes in the gut microbiota have been reported and have been linked to disease progression. Here, we review evidence for the role of the gut microbiota in intestinal homeostasis, its contribution to HIV pathogenesis, as well as its use in the development of therapeutic strategies.

scholarly journals Gut Microbiota-Derived Inosine From Dietary Barley Leaf Supplementation Attenuates Colitis Through PPARγ Signaling Activation

2021 ◽  
Author(s):  
Daotong Li ◽  
Yu Feng ◽  
Meiling Tian ◽  
Junfu Ji ◽  
Xiaosong Hu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Mucosal Barrier ◽  
Chronic Inflammatory Bowel Disease ◽  
Rrna Gene ◽  
Intestinal Homeostasis ◽  
Potential Health ◽  
Barrier Functions ◽  
Barley Leaf ◽  
Purine Metabolite ◽  
Gut Microbiota Dysbiosis

Abstract Background Ulcerative colitis is a type of chronic inflammatory bowel disease closely associated with gut microbiota dysbiosis and intestinal homeostasis dysregulation. Barley leaf (BL) has a long history of use in Traditional Chinese Medicine with potential health-promoting effects on intestinal functions. However, its mechanism of action is not yet clear. Here, we explore the potential modulating roles of gut microbial metabolites of BL to protect against colitis and elucidate the underlying molecular mechanisms. Results Using 16S rRNA gene-based microbiota analysis, we first found that dietary supplementation of BL ameliorated dextran sulphate sodium (DSS)-induced gut microbiota dysbiosis. The mechanisms by which BL protected against DSS-induced colitis were resulted from improved intestinal mucosal barrier functions via the activation of peroxisome proliferator-activated receptor (PPAR)γ signaling. In addition, metabolomic profiling analysis showed that the gut microbiota modulated BL-induced metabolic reprograming in the colonic tissues particularly by the enhancement of glycolysis process. Notably, dietary BL supplementation resulted in enrichment of microbiota-derived purine metabolite inosine, which could activate PPARγ signaling in human colon epithelial cells. Furthermore, exogenous treatment of inosine reproduced the similar protective effects as BL to protect against DSS-induced colitis through improving adenosine 2A receptor (A2AR)/PPARγ-dependent mucosal barrier functions. Conclusions Overall, our findings suggest that the gut microbiota-inosine-A2AR/PPARγ axis plays an important role in the maintenance of intestinal homeostasis, which may represent a novel approach for colitis prevention via manipulation of the gut microbial purine metabolite.

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