376 – Interleukin-33 Promotes Reg3G Expression in Intestinal Epithelial Cells and Regulates Gut Microbiota

Abstract BackgroundThe interplay of long-non coding RNAs (lncRNAs) and the intestinal microbiota may serve as an essential role in intestinal development and homeostasis. Microbiota could regulate a large numbers of lncRNAs expression in intestinal epithelial cells. However, the associations between lncRNAs and microbiota during early postnatal development stages are still need to understand. MethodsIn present study, the microbial effects on lncRNA of intestinal epithelial cells (IECs) during postnatal development stage were investigated. ResultsWe identified gut microbiota-specific lncRNAs in diverse postnatal development stages including week 1, week 4 and week 12/16 of mice. A large proportion of gut microbiota-specific lncRNAs only were differential expressed in a single postnatal development stage. Up- and down-regulated gut microbiota-specific lncRNAs both showed consistent expression pattern. We also constructed gut microbiota-specific lncRNAs and coding genes interacted co-expressed networks. Functional analysis indicated that gut microbiota-specific lncRNAs were associated with ABC transporters. ConclusionsIn summary, the present study characterizes the landscape of lncRNAs associated with gut microbiota in different postnatal development stages. It provide assistance for exploring the relationships among lncRNAs, gut microbiota and postnatal development stages.

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Faecal microRNAs: indicators of imbalance at the host-microbe interface?

Beneficial Microbes ◽

10.3920/bm2017.0013 ◽

2018 ◽

Vol 9 (2) ◽

pp. 175-183 ◽

Cited By ~ 18

Author(s):

G.M. Moloney ◽

M.F. Viola ◽

A.E. Hoban ◽

T.G. Dinan ◽

J.F. Cryan

Keyword(s):

Epithelial Cells ◽

Gut Microbiota ◽

Antibiotic Treatment ◽

Mirna Expression ◽

Intestinal Epithelial Cells ◽

Intestinal Epithelial ◽

Sprague Dawley ◽

Faecal Pellets ◽

Non Invasive ◽

Bodily Fluids

The enteric microbiota is characterised by a balance and composition that is unique to the host. It is important to understand the mechanisms through which the host can maintain the composition of the gut microbiota. MicroRNAs (miRNA) are implicated in intercellular communication and have been isolated from bodily fluids including stool. Recent findings suggest that miRNA produced by the host’s intestinal epithelial cells (IECs) participate in shaping the microbiota. To investigate whether miRNA expression was influenced by the gut microbiota we measured the expression of miRNAs expressed by intestinal epithelial cells in faeces. Specifically, we measured miRNA expression in faeces from germ-free (GF) and conventional mice and similarly in a rat model of antibiotic-mediated depletion of the gut microbiota control rats. In adult male GF and conventional mice and adult Sprague Dawley (SD) rats were treated with a combination of antibiotics for 8 weeks; total RNA was extracted from faecal pellets taken at week 0, 2, 4, 6 week 8 and the expression of let-7b-3p, miR-141-3p, miR-200a-3p and miR-1224-5p (miRNAs known to be expressed in IECs) were measured relative to U6 at each time point using qRT-PCR. In GF animals the expression of let-7b, miR-141 and miR-200a in faeces was lower compared to conventional mice. Following antibiotic-mediated depletion of gut microbiota, rats showed two divergent profiles of miRNA expression. Following two weeks of antibiotic treatment, the expression of let-7b and miR-1224 dropped significantly and remained low for the remainder of the study. The expression of miR-200a and miR-141 was significantly higher at week 2 than before antibiotic treatment commenced. Subsequently, the expression of miR-200a and miR-141 decreased at week 4 and continued to decrease at week 6. This data demonstrates that miRNAs can be used as an independent, non-invasive marker of microbial fluctuations along with gut pathology in the intestine.

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Gut Microbiota Dysbiosis in Systemic Lupus Erythematosus: Novel Insights into Mechanisms and Promising Therapeutic Strategies

Frontiers in Immunology ◽

10.3389/fimmu.2021.799788 ◽

2021 ◽

Vol 12 ◽

Author(s):

Quanren Pan ◽

Fengbiao Guo ◽

Yanyan Huang ◽

Aifen Li ◽

Shuxian Chen ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Epithelial Cells ◽

Gut Microbiota ◽

Lupus Erythematosus ◽

Intestinal Epithelial Cells ◽

Therapeutic Strategies ◽

Oral Antibiotic ◽

Intestinal Epithelial ◽

Systemic Lupus ◽

Gut Microbiota Dysbiosis

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that was traditionally thought to be closely related to genetic and environmental risk factors. Although treatment options for SLE with hormones, immunosuppressants, and biologic drugs are now available, the rates of clinical response and functional remission of these drugs are still not satisfactory. Currently, emerging evidence suggests that gut microbiota dysbiosis may play crucial roles in the occurrence and development of SLE, and manipulation of targeting the gut microbiota holds great promises for the successful treatment of SLE. The possible mechanisms of gut microbiota dysbiosis in SLE have not yet been well identified to date, although they may include molecular mimicry, impaired intestinal barrier function and leaky gut, bacterial biofilms, intestinal specific pathogen infection, gender bias, intestinal epithelial cells autophagy, and extracellular vesicles and microRNAs. Potential therapies for modulating gut microbiota in SLE include oral antibiotic therapy, fecal microbiota transplantation, glucocorticoid therapy, regulation of intestinal epithelial cells autophagy, extracellular vesicle-derived miRNA therapy, mesenchymal stem cell therapy, and vaccination. This review summarizes novel insights into the mechanisms of microbiota dysbiosis in SLE and promising therapeutic strategies, which may help improve our understanding of the pathogenesis of SLE and provide novel therapies for SLE.

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Exposure to the gut microbiota drives distinct methylome and transcriptome changes in intestinal epithelial cells during postnatal development

Genome Medicine ◽

10.1186/s13073-018-0534-5 ◽

2018 ◽

Vol 10 (1) ◽

Cited By ~ 44

Author(s):

Wei-Hung Pan ◽

Felix Sommer ◽

Maren Falk-Paulsen ◽

Thomas Ulas ◽

Philipp Best ◽

...

Keyword(s):

Epithelial Cells ◽

Gut Microbiota ◽

Postnatal Development ◽

Intestinal Epithelial Cells ◽

Intestinal Epithelial

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Commensal Escherichia coli Aggravates Acute Necrotizing Pancreatitis through Targeting of Intestinal Epithelial Cells

Applied and Environmental Microbiology ◽

10.1128/aem.00059-19 ◽

2019 ◽

Vol 85 (12) ◽

Cited By ~ 5

Author(s):

Junyuan Zheng ◽

Lihong Lou ◽

Junjie Fan ◽

Chunlan Huang ◽

Qixiang Mei ◽

...

Keyword(s):

Escherichia Coli ◽

Epithelial Cells ◽

Gut Microbiota ◽

Intestinal Epithelial Cells ◽

Necrotizing Pancreatitis ◽

Intestinal Barrier ◽

Intestinal Epithelial ◽

Content Type ◽

E Coli ◽

Acute Necrotizing

ABSTRACT An increase of Escherichia-Shigella was previously reported in acute necrotizing pancreatitis (ANP). We investigated whether Escherichia coli MG1655, an Escherichia commensal organism, increased intestinal injury and aggravated ANP in rats. ANP was induced by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct. Using gut microbiota-depleted rats, we demonstrated that gut microbiota was involved in the pancreatic injury and intestinal barrier dysfunction in ANP. Using 16S rRNA gene sequencing and quantitative PCR, we found intestinal dysbiosis and a significant increase of E. coli MG1655 in ANP. Afterward, administration of E. coli MG1655 by gavage to gut microbiota-depleted rats with ANP was performed. We observed that after ANP induction, E. coli MG1655-monocolonized rats presented more severe injury in the pancreas and intestinal barrier function than gut microbiota-depleted rats. Furthermore, Toll-like receptor 4 (TLR4)/MyD88/p38 mitogen-activated protein (MAPK) and endoplasmic reticulum stress (ERS) activation in intestinal epithelial cells were also increased more significantly in the MG1655-monocolonized ANP rats. In vitro, the rat ileal epithelial cell line IEC-18 displayed aggravated tumor necrosis factor alpha-induced inflammation and loss of tight-junction proteins in coculture with E. coli MG1655, as well as TLR4, MyD88, and Bip upregulation. In conclusion, our study shows that commensal E. coli MG1655 increases TLR4/MyD88/p38 MAPK and ERS signaling-induced intestinal epithelial injury and aggravates ANP in rats. Our study also describes the harmful potential of commensal E. coli in ANP. IMPORTANCE This study describes the harmful potential of commensal E. coli in ANP, which has not been demonstrated in previous studies. Our work provides new insights into gut bacterium-ANP cross talk, suggesting that nonpathogenic commensals could also exhibit adverse effects in the context of diseases.

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