Dataset Information

Multi-omics uncovers formononetin's protection against antibiotic-induced liver injury via microbiota-metabolite-transcriptome coordination

ABSTRACT:

Tetracycline antibiotics (TETs) cause hepatotoxicity via gut-liver axis disruption and oxidative stress. This study evaluated whether formononetin (FMN), a natural isoflavone, alleviates TET-induced liver injury through microbiota-metabolite-transcriptome coordination. Using network toxicology and pharmacology, we predicted key targets and pathways involved. A mouse model of TET-induced injury (150 mg/kg, 3 days) was treated with FMN (50 or 100 mg/kg) for 14 days. Multi-omics analyses revealed that FMN attenuated hepatic steatosis, reduced ALT/AST levels, enhanced gut microbial diversity (enriched Limosilactobacillus), and restored intestinal barrier integrity. Mechanistically, FMN activated the Nrf2/HO-1 antioxidant pathway, modulated PPARα/CYP2E1-dependent lipid metabolism, and inhibited ferroptosis. FMN demonstrates multi-target hepatoprotection by coordinating microbiota restoration, oxidative stress reduction, and metabolic reprogramming, supporting its potential as a dietary intervention against antibiotic-related liver damage.

INSTRUMENT(S): Liquid Chromatography MS - positive - HILIC, Liquid Chromatography MS - negative - HILIC

PROVIDER: MTBLS13138 | MetaboLights | 2025-10-14

REPOSITORIES: MetaboLights

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	a_MTBLS13138_LC-MS_negative_hilic_metabolite_profiling.txt	Txt
	a_MTBLS13138_LC-MS_positive_hilic_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS13138_LC-MS_negative_hilic_metabolite_profiling_v2_maf.tsv	Tabular
	m_MTBLS13138_LC-MS_positive_hilic_metabolite_profiling_v2_maf.tsv	Tabular

Items per page:

1 - 5 of 6

Similar Datasets

Project description:Renal hypoxia is widespread in acute kidney injury (AKI) of various aetiologies. Hypoxia adaptation, conferred through the hypoxia-inducible factor (HIF), appears to be insufficient. Here we show that HIF activation in renal tubules through Pax8-rtTA-based inducible knockout of von Hippel-Lindau protein (VHL-KO) protects from rhabdomyolysis-induced AKI. In this model, histological observations indicate that injury mainly affects proximal convoluted tubules, with 5% necrosis at d1 and 40% necrosis at d2. HIF-1alpha up-regulation in distal tubules reflects renal hypoxia. However, lack of HIF in proximal tubules suggests insufficient adaptation by HIF. AKI in VHL-KO mice leads to prominent HIF activation in all nephron segments, as well as to reduced serum creatinine, serum urea, tubular necrosis, and apoptosis marker caspase-3 protein. At d1 after rhabdomyolysis, when tubular injury is potentially reversible, HIF mediated protection in AKI is associated with activated glycolysis, cellular glucose uptake and utilization, autophagy, vasodilation, and proton removal as demonstrated by qPCR, pathway enrichment analysis and immunohistochemistry. Together, our data provide evidence for a HIF-orchestrated multi-level shift towards glycolysis as a major mechanism for protection against acute tubular injury. All experiments were carried out in transgenic mice in which selective renal tubular VHL knockout (VHL-KO) was inducible by doxycycline (Reference: Mathia S, Paliege A, Koesters R, Peters H, Neumayer HH, Bachmann S, Rosenberger C. Action of hypoxia-inducible factor in liver and kidney from mice with Pax8-rtTA-based deletion of von Hippel-Lindau protein. Acta Physiol (Oxf). 2013; 207(3):565-76.). Four groups of animals were used: 1) controls: untreated mice; 2) VHL-KO: injected with doxycycline (0.1 mg per 10 g body weight SC), 4 days prior to sacrifice; 3) AKI: rhabdomyolysis; 4) VHL-KO/AKI: doxycycline plus rhabdomyolysis. To induce AKI, 50% glycerol (0.05 ml per 10 g body weight) was injected IM into the left hind limb under isoflurane narcosis. Drinking water was withdrawn between 20 h prior and 24 h after glycerol injection.

Dataset Information

Multi-omics uncovers formononetin's protection against antibiotic-induced liver injury via microbiota-metabolite-transcriptome coordination

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets