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Gut microbiota-derived GlcNAc-MurNAc is a TLR4 agonist that protects the host gut

ABSTRACT: Gut microbiota-derived GlcNAc-MurNAc is a TLR4 agonist that protects the host gut

PROVIDER: PRJNA1269026 | ENA |

REPOSITORIES: ENA

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			Action	DRS
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	SRR33734835_1.fastq.gz	Fastqsanger.gz
	SRR33734835_2.fastq.gz	Fastqsanger.gz
	SRR33734836_1.fastq.gz	Fastqsanger.gz
	SRR33734836_2.fastq.gz	Fastqsanger.gz

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Gut microbiota-derived GlcNAc-MurNAc is a TLR4 agonist that protects the host gut

Project description:Gut microbiota-derived peptidoglycan fragments (PGNs) are key signaling molecules that regulate multiple aspects of the host’s health. Yet the exact structures of natural PGNs in hosts have not been fully elucidated. Herein, we developed an LC-HRMS/MS analytical platform for global quantification and profiling of natural PGN subtypes in host gut and sera, unexpectedly revealing the abundance of PGN-derived saccharide moieties that do not resemble canonical ligands of mammalian NOD1/2 receptors. Focusing on the disaccharide GlcNAc-MurNAc (GM), which does not activate NOD1/2 yet still exhibits immunostimulatory effects in host immune cells, we established GM as a mild TLR4 agonist, illustrating an alternate PGN sensing mechanism other than NOD signaling. Importantly, the administration of GM mitigates colonic inflammation in the DSS-induced colitis model in mice via a TLR4-dependent manner, highlighting the in vivo significance of gut microbiota-derived PGN saccharides in maintaining host intestinal homeostasis.

2025-05-28 | GSE298370 | GEO

Study of Intratumoral Ipilimumab and TLR4 Agonist GLA-SE in Combination With Systemic Nivolumab and Chemotherapy

Project description:To determine the maximum tolerated dose (MTD), the recommended phase 2 dose (RP2D) and the toxicity profile (NCI CTCAE v5.0 and immune related adverse events) of i.t. administration of anti-CTLA4 antibody (ipilimumab) and TLR4 agonist (synthetic glucopyranosyl lipid A formulated in a stable emulsion [GLA-SE]) in colorectal LM (CRLM) in combination with intravenous (i.v.) administration of anti-PD-1 antibody (nivolumab) and chemotherapy (FOLFOX regimen).

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Intratumoral injection of TLR4 agonist GLA in A20 tumor model

Project description:The goal of this study was to investigate the effect of intratumoral injection of GLA-SE, a TLR4 agonist in stable emulsion (SE), in Balb/c mice with established A20 lymphoma.

2020-08-04 | GSE150457 | GEO

The protective role of TLR4 in intestinal epithelial cells through the regulation of the gut microbiota in DSS-induced colitis in mice

Project description:Abstract. Background: The cause of ulcerative colitis (UC) is not yet fully understood. Previous research has pointed towards a potential role for mutations in NOD2 in promoting the onset and progression of inflammatory bowel disease (IBD) by altering the microbiota of the gut. However, the relationship between toll-like receptor 4 (TLR4) and gut microbiota in IBD is not well understood. To shed light on this, the interaction between TLR4 and gut microbiota was studied using a mouse model of IBD. Methods: To examine the function of TLR4 signaling in intestinal injury repair, researchers developed Dextran Sulfate Sodium Salt (DSS)-induced colitis and injury models in both wild-type (WT) mice and TLR4 knockout (TLR4-KO) mice. To assess changes in the gut microbiota, 16S rRNA sequencing was conducted on fecal samples from both the TLR4-KO and WT enteritis mouse models. Results: The data obtained depicted a protective function of TLR4 against DSS-induced colitis. The gut microbiota composition was found to vary considerably between the WT and TLR4-KO mice groups as indicated by β-diversity analysis and operational taxonomic units (OTUs) cluster. Statistical analysis of microbial multivariate variables depicted an elevated abundance of Escherichia coli/Shigella, Gammaproteobacteria, Tenerlcutes, Deferribacteres, Enterobacteria, Rikenellaceae, and Proteobacteria in the gut microbiota of TLR4-KO mice, whereas there was a considerable reduction in Bacteroidetes at five different levels of the phylogenetic hierarchy including phylum, class, order, family, and genus in comparison with the WT control. Conclusion: TLR4 may protect intestinal epithelial cells from damage in response to DSS-induced injury by controlling the microbiota in the gut.

2023-11-01 | GSE227565 | GEO

Intratumoral injection of TLR4 agonist GLA in A20 tumor model

Project description:Intratumoral injection of TLR4 agonist GLA in A20 tumor model

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Dietary fatty acids interact with gut microbiota and TLR4 to promote colitis and colorectal tumorigenesis

Project description:We show that oxidized LA, rather than LA itself,exacerbates colitis via Toll-like receptor 4 (TLR4)- and gut microbiota-dependent mechanisms.Administration of a diet containing oxidized LA, at low human-consumption levels, increases the severity of colitis and exacerbates the development of colorectal tumorigenesis in mice.

2023-12-31 | GSE209580 | GEO

Immunoresponsive Gene 1 Facilitates TLR4-agonist-Induced Augmentation of Innate Antimicrobial Immunity

Project description:Immunoresponsive Gene 1 Facilitates TLR4-agonist-Induced Augmentation of Innate Antimicrobial Immunity

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Characterization of a gut-restricted LXR agonist and its utility in ameliorating liver injury in experimental short gut syndrome

Project description:Short bowel syndrome (SBS) results from the surgical removal of extensive portions of the small intestine and is associated with high morbidity, including intestinal failure-associated liver disease (IFALD). We aim to identify effective, targeted therapies to combat IFALD while promoting small intestinal remodeling that optimizes intestinal health and nutrient absorption. Following previous findings that an LXR agonist administered orally suppresses liver injury in a mouse model of SBS, we sought application of a gut-restricted LXR agonist to avoid potential for systemic activation of LXR. We synthesized and characterized WUSTL0717 as a potential gut-restricted hydrophobic derivative of the well-known LXR agonist GW3965and tested its ability to improve outcomes in a mouse model of SBS. Pharmacokinetic analysis in mice revealed overwhelming intestinal retention of WUSTL0717. The compound activated a panoply of LXR target genes, including Abca1, in the small intestine but not the liver. It also increased ileal transcript levels of Apoa1 that encodes the core protein of high-density lipoprotein (HDL) and raised HDL levels in plasma. WUSTL0717 was efficacious in protecting against IFALD. Additionally, WUSTL0717 improved nutrient absorption after small intestinal resection and promoted restoration of body weight. These data identify the LXR agonist WUSTL0717 as a gut-restricted drug that may provide therapeutic benefits for treating SBS-associated IFALD while avoiding unwanted effects of systemic LXR agonists.

2026-01-18 | GSE287046 | GEO

Molecular and cellular response profiles induced by the TLR4 agonist-based adjuvant Glucopyranosyl Lipid A

Project description:Toll-like receptor (TLR)4 agonists are known potent immunostimulatory compounds. These compounds can be formulated as part of novel adjuvants to enhance vaccine medicated immune responses. However, the contribution of the formulation to the innate in vivo activity of TLR4 agonist compounds is not well understood. Molecular expression profiles and cellular responses in a mouse model were used to compare for GLA-SE, GLA, Alum, SE, PBS. This study was to evaluate the mechanism of actions of different adjuvants and to identify potential biomarkers for clinical evaluation.

2013-01-09 | GSE43373 | GEO

Molecular and cellular response profiles induced by the TLR4 agonist-based adjuvant Glucopyranosyl Lipid A

2013-01-09 | E-GEOD-43373 | biostudies-arrayexpress