Indole‐3‐Lactic Acid Inhibits Doxorubicin‐Induced Ferroptosis Through Activating Aryl Hydrocarbon Receptor/Nrf2 Signalling Pathway DOI Creative Commons
Jiangfang Lian, Hangyuan Guo,

Zuoquan Zhong

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(2)

Published: Jan. 1, 2025

ABSTRACT The clinical application of doxorubicin (DOX) is limited due to its cardiotoxicity, which primarily attributed interaction with iron in mitochondria, leading lipid peroxidation and myocardial ferroptosis. This study aimed investigate the role gut microbiota‐derived metabolite, indole‐3‐lactic acid (ILA), mitigating DOX‐induced cardiotoxicity (DIC). Cardiac function, pathological changes, ferroptosis were assessed vivo. cardioprotective effects mechanisms ILA explored using multi‐omics approaches, including single‐nucleus RNA sequencing (snRNA‐seq) bulk RNA‐seq, further validated Nrf2 knockout mice. findings revealed that DOX treatment disrupted microbiota, significantly reducing levels tryptophan metabolite ILA. In DIC models, supplementation markedly improved cardiac reduced collagen deposition, mitigated atrophy. snRNA‐seq analyses indicated played a crucial Experimental data demonstrated decreased both mice DOX‐treated H9C2 cells, evidenced by restoration GPX4 SLC7A11 reduction ACSL4. Mechanistically, functions as ligand for aryl hydrocarbon receptor (AhR), upregulation expression. protective against abolished silencing AhR. Moreover, beneficial on eliminated Nrf2‐deficient conclusion, exerts therapeutic inhibiting through activation AhR/Nrf2 signalling pathway. Identifying microbial could offer viable strategies DIC.

Language: Английский

Microbial aromatic amino acid metabolism is modifiable in fermented food matrices to promote bioactivity DOI Creative Commons

Mikaela C. Kasperek,

Adriana Velasquez Galeas,

Maria Elisa Caetano‐Silva

et al.

Food Chemistry, Journal Year: 2024, Volume and Issue: 454, P. 139798 - 139798

Published: May 22, 2024

Ingestion of fermented foods impacts human immune function, yet the bioactive food components underlying these effects are not understood. Here, we interrogated whether bioactivity relates to microbial metabolites derived from aromatic amino acids, termed aryl-lactates. Using targeted metabolomics, established presence aryl-lactates in commercially available foods. After pinpointing food-associated lactic acid bacteria that produce high levels aryl-lactates, identified fermentation conditions increase aryl-lactate production matrices up 5 × 10

Language: Английский

Citations

9
Gut microbiota contributes to high-altitude hypoxia acclimatization of human populations DOI Creative Commons

Qian Su,

Daohua Zhuang,

Yuchun Li

et al.

Genome biology, Journal Year: 2024, Volume and Issue: 25(1)

Published: Aug. 28, 2024

The relationship between human gut microbiota and high-altitude hypoxia acclimatization remains highly controversial. This stems primarily from uncertainties regarding both the potential temporal changes in under such conditions existence of any dominant or core bacteria that may assist host acclimatization.

Language: Английский

Citations

9
The role of microbial indole metabolites in tumor DOI Creative Commons
Dingjiacheng Jia, Zheng Kuang, Liangjing Wang

et al.

Gut Microbes, Journal Year: 2024, Volume and Issue: 16(1)

Published: Oct. 1, 2024

The gut microbiota can produce a variety of microbial-derived metabolites to influence tumor development. Tryptophan, an essential amino acid in the human body, be converted by microorganisms via indole pathway such as Indole-3-Lactic Acid (ILA), Indole-3-Propionic (IPA), Indole Acetic (IAA) and Indole-3-Aldehyde (IAld). Recent studies have shown that play key roles progression, they used adjuvant regimens for immunotherapy or chemotherapy. Here, we summarize recent findings on common microbial provide review mechanisms different microenvironment. We further discuss limitations current metabolite research future possibilities. It is expected will new strategies clinical therapy.

Language: Английский

Citations

9
Polystyrene nanoplastics promote colitis-associated cancer by disrupting lipid metabolism and inducing DNA damage DOI Creative Commons
Shan Tian, Ruixue Li, Jiao Li

et al.

Environment International, Journal Year: 2025, Volume and Issue: 195, P. 109258 - 109258

Published: Jan. 1, 2025

Nanoplastics (NPs) have attracted widespread attention owing to their presence in the body. Recent studies highlighted detrimental effects of NPs on digestive tract. However, no reported an association between exposure and colitis-associated cancer (CAC). An azoxymethane/dextran sodium sulfate-induced CAC model was used, polystyrene nanoparticles (PS-NPs) were selected for long-term exposure. Non-targeted metabolomics 16S rRNA sequencing used detect changes colonic metabolites gut microbes following PS-NPs A lipopolysaccharide (LPS)-treated cell (Caco-2) exposed investigate underlying molecular mechanism. Compared normal control group, mice group exhibited more tumor nodes reactive oxygen species (ROS), higher expression pan-CK Ki-67, severe DNA damage. revealed that altered abundance Allobaculum Lactobacillus, whereas metabolic analysis showed most significant enriched mostly fatty acid metabolism. Experiments LPS intervened Caco-2 cells led lipid peroxidation, oxidative stress, damage Caco-2. Exposure activated phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target rapamycin (mTOR) signaling pathway both AOM/DSS mouse cellular model. Key proteins involved metabolism downregulated PS-NPs. The significantly inhibited by activation fenofibrate. disturbed induced via PI3K/AKT/mTOR promote progression. Inhibition is a therapeutic controlling PS-NP-induced CAC. Our study provides important reference prevention treatment from perspective environment enhances awareness necessity plastic control.

Language: Английский

Citations

1
Indole‐3‐Lactic Acid Inhibits Doxorubicin‐Induced Ferroptosis Through Activating Aryl Hydrocarbon Receptor/Nrf2 Signalling Pathway DOI Creative Commons
Jiangfang Lian, Hangyuan Guo,

Zuoquan Zhong

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(2)

Published: Jan. 1, 2025

ABSTRACT The clinical application of doxorubicin (DOX) is limited due to its cardiotoxicity, which primarily attributed interaction with iron in mitochondria, leading lipid peroxidation and myocardial ferroptosis. This study aimed investigate the role gut microbiota‐derived metabolite, indole‐3‐lactic acid (ILA), mitigating DOX‐induced cardiotoxicity (DIC). Cardiac function, pathological changes, ferroptosis were assessed vivo. cardioprotective effects mechanisms ILA explored using multi‐omics approaches, including single‐nucleus RNA sequencing (snRNA‐seq) bulk RNA‐seq, further validated Nrf2 knockout mice. findings revealed that DOX treatment disrupted microbiota, significantly reducing levels tryptophan metabolite ILA. In DIC models, supplementation markedly improved cardiac reduced collagen deposition, mitigated atrophy. snRNA‐seq analyses indicated played a crucial Experimental data demonstrated decreased both mice DOX‐treated H9C2 cells, evidenced by restoration GPX4 SLC7A11 reduction ACSL4. Mechanistically, functions as ligand for aryl hydrocarbon receptor (AhR), upregulation expression. protective against abolished silencing AhR. Moreover, beneficial on eliminated Nrf2‐deficient conclusion, exerts therapeutic inhibiting through activation AhR/Nrf2 signalling pathway. Identifying microbial could offer viable strategies DIC.

Language: Английский

Citations

1