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

Targeting gut microbiota and metabolism as the major probiotic mechanism - An evidence-based review DOI Creative Commons
Teng Ma, Xin Shen, Xuan Shi

et al.

Trends in Food Science & Technology, Journal Year: 2023, Volume and Issue: 138, P. 178 - 198

Published: June 11, 2023

The human gut hosts complex microbial communities, which are linked to health and disease. microbiota is continuously reshaped by multiple environmental factors, especially diet. Gut dysbiosis may promote various metabolic, neurological, intestinal, cardiovascular diseases, even tumor development. Probiotics have shown promising prophylactic, mitigating, or curative effects when use as nutrient supplements adjunctive therapy. These beneficial and/or symptom alleviation often accompanied microbiome metabolome changes. Differing from other published review articles, here we summarized the latest knowledge of evidence-based health-promoting probiotics scouring literature recent animal probiotic intervention studies. To elucidate mechanisms in enhancing intestinal homeostasis, barrier function, host immunity, through modulating its metabolites. Meanwhile, also discussed challenges data analysis clinical research comparison between laboratories, provides an outlook for future perspectives applications probiotics. achieved modulation. Current discussed. Finally, provided.

Language: Английский

Citations

146
Intratumoural microbiota: a new frontier in cancer development and therapy DOI Creative Commons

Yaqi Cao,

Hui Xia,

Xueyun Tan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Jan. 10, 2024

Abstract Human microorganisms, including bacteria, fungi, and viruses, play key roles in several physiological pathological processes. Some studies discovered that tumour tissues once considered sterile actually host a variety of which have been confirmed to be closely related oncogenesis. The concept intratumoural microbiota was subsequently proposed. Microbiota could colonise through mucosal destruction, adjacent tissue migration, hematogenic invasion affect the biological behaviour tumours as an important part microenvironment. Mechanistic demonstrated potentially promote initiation progression by inducing genomic instability mutations, affecting epigenetic modifications, promoting inflammation response, avoiding immune regulating metabolism, activating metastasis. Since more comprehensive profound insights about intratumoral are continuously emerging, new methods for early diagnosis prognostic assessment cancer patients under examination. In addition, interventions based on show great potential open chapter antitumour therapy, especially immunotherapy, although there some inevitable challenges. Here, we aim provide extensive review concept, development history, sources, heterogeneity, carcinogenic mechanisms explore role microorganisms prognosis, discuss current treatment regimens target research prospects limitations this field.

Language: Английский

Citations

69
Gut microbial metabolite facilitates colorectal cancer development via ferroptosis inhibition DOI
Weiwei Cui, Meng Guo, Dong Liu

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(1), P. 124 - 137

Published: Jan. 1, 2024

Language: Английский

Citations

67
The emerging role of lactate in tumor microenvironment and its clinical relevance DOI

Sihan Chen,

Yining Xu,

Wei Zhuo

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 590, P. 216837 - 216837

Published: March 26, 2024

Language: Английский

Citations

30
A multi-dimensional approach to unravel the intricacies of lactylation related signature for prognostic and therapeutic insight in colorectal cancer DOI Creative Commons
Huixia Huang, Keji Chen, Yifei Zhu

et al.

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 28, 2024

Abstract Background Lactylation, a novel contributor to post-translational protein modifications, exhibits dysregulation across various tumors. Nevertheless, its intricate involvement in colorectal carcinoma, particularly for non-histone lactylation and intersection with metabolism immune evasion, remains enigmatic. Methods Employing immunohistochemistry on tissue microarray clinical information immunofluorescence cell lines, we investigated the presence of global association development progression cancer as well functional location. Leveraging AUCell algorithm alongside correlation analysis single-cell RNA sequencing data, cox-regression lasso-regression TCGA dataset confirmed GEO dataset, identified 23-gene signature predicting prognosis. Subsequently, analyzed associations between related gene risk characteristics, mutation landscapes, biological functions, infiltration, immunotherapy responses, drug sensitivity. Core genes were further explored deep insights through bioinformatics vitro experiments. Results Our study innovatively reveals significant elevation cancer, malignant tumors, confirming it an independent prognostic factor CRC. Through comprehensive integrating tumor arrays, combining silico investigations experiments, Lactylation-Related Gene model capable prognosis patients. Noteworthy variations observed checkpoint expression, responses sensitivity among distinct groups. Conclusions The potential improving management patients enhancing therapeutic outcomes, at evasion. This finding underscores relevance CRC lays groundwork mechanism investigation targeted strategies given high lactate concentration

Language: Английский

Citations

22
Bifidobacterium breve-derived indole-3-lactic acid ameliorates colitis-associated tumorigenesis by directing the differentiation of immature colonic macrophages DOI Creative Commons
Yuke Li, Qingxiang Li,

Ruoshui Yuan

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(7), P. 2719 - 2735

Published: Jan. 1, 2024

Aim: To elucidate dynamics and functions in colonic macrophage subsets, their regulation by Bifidobacterium breve (B.breve) its associated metabolites the initiation of colitis-associated colorectal cancer (CAC).Methods: Azoxymethane (AOM) dextran sodium sulfate (DSS) were used to create a CAC model.The tumor-suppressive effect B. variations subsets evaluated.Intestinal macrophages ablated determine role protective effects breve.Efficacious molecules produced identified non-targeted targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis.The molecular mechanism was further verified murine bone marrow-derived (BMDMs), derived from human peripheral blood mononuclear cells (hPBMCs), demonstrated mice.Results: alleviated colitis symptoms, delayed tumorigenesis, promoted phenotypic differentiation immature inflammatory into mature homeostatic macrophages.On contrary, ablation intestinal largely annulled breve.Microbial analysis contents revealed enrichment probiotics depletion potential pathogens following supplementation.Moreover, indole-3-lactic acid (ILA) positively correlated with mice highly enriched culture supernatant breve.Also, addition ILA directly AKT phosphorylation restricted pro-inflammatory response BMDMs hPBMCs vitro.The abolished aryl hydrocarbon receptor (AhR) antagonist CH-223191 or inhibitor MK-2206.Furthermore, could protect against tumorigenesis regulating mice; AhR abrogated relieving tumorigenesis.Conclusion: breve-mediated tryptophan metabolism ameliorates precancerous milieu inhibit directing macrophages.

Language: Английский

Citations

22
Probiotic significance of Lactobacillus strains: a comprehensive review on health impacts, research gaps, and future prospects DOI Creative Commons
Abdul Bari Shah, Aizhamal Baiseitova, Muhammad Zahoor

et al.

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

Published: Nov. 24, 2024

A rising corpus of research has shown the beneficial effects probiotic

Language: Английский

Citations

16
Innovative Applications of Bacteria and Their Derivatives in Targeted Tumor Therapy DOI

Denghui Zhu,

Wei Pan,

Heqi Li

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Despite significant progress in cancer treatment, traditional therapies still face considerable challenges, including poor targeting, severe toxic side effects, and the development of resistance. Recent advances biotechnology have revealed potential bacteria their derivatives as drug delivery systems for tumor therapy by leveraging biological properties. Engineered bacteria, Escherichia coli, Salmonella, Listeria monocytogenes, along with derivatives─outer membrane vesicles (OMVs), bacterial ghosts (BGs), spores (BSPs)─can be loaded a variety antitumor agents, enabling precise targeting sustained release within microenvironment (TME). These possess intrinsic properties that stimulate immune system, enhancing both innate adaptive responses to further amplify therapeutic effects. The ability naturally accumulate hypoxic regions versatility genetic modifications allow tailored strategies synergistically enhance effectiveness chemotherapy, immunotherapy, targeted therapies. This review comprehensively examines fundamental principles therapy, focusing on employed engineering, loading, use therapy. It also discusses challenges faced optimizing systems, such safety concerns, unintended responses, scalability clinical applications. By exploring these aspects, this provides theoretical framework improving bacterial-based contributing more effective personalized treatments.

Language: Английский

Citations

3
Advancements in Lactiplantibacillus plantarum : probiotic characteristics, gene editing technologies and applications DOI Creative Commons
Zhiqi Zhang, Huifeng Niu,

Qiu Qu

et al.

Critical Reviews in Food Science and Nutrition, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 22

Published: Jan. 2, 2025

The exploration of microorganisms in fermented products has become a pivotal area scientific research, primarily due to their widespread availability and profound potential improve human health. Among these, Lactiplantibacillus plantarum (formerly known as Lactobacillus plantarum) stands out versatile lactic acid bacterium, prevalent across diverse ecological niches. Its appeal extends beyond its well-documented probiotic benefits include the remarkable plasticity genome, which captivated both industrial stakeholders. Despite this interest, substantial challenges persist fully understanding harnessing L. plantarum. This review aims illuminate attributes plantarum, consolidate current advancements gene editing technologies, explore multifaceted applications wild-type genetically engineered strains.

Language: Английский

Citations

2
Bacterial indole-3-lactic acid affects epithelium–macrophage crosstalk to regulate intestinal homeostasis DOI Creative Commons
Kaiyuan Yu, Qianqian Li,

Xuan Sun

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(45)

Published: Oct. 30, 2023

Tryptophan and its derivatives perform a variety of biological functions; however, the role specific mechanism many tryptophan in intestinal inflammation remain largely unclear. Here, we identified that an Escherichia coli strain ( Ec- TMU) isolated from feces tinidazole-treated individuals, indole-3-lactic acid (ILA) supernatant, decreased susceptibility mice to dextran sulfate sodium–induced colitis. TMU ILA contribute relief colitis by inhibiting production epithelial CCL2/7, thereby reducing accumulation inflammatory macrophages vitro vivo. Mechanistically, downregulates glycolysis, NF-κB, HIF signaling pathways via aryl hydrocarbon receptor, resulting CCL2/7 cells. Clinical evidence suggests fecal level is negatively correlated with progression indicator bowel diseases. These results demonstrate has potential regulate homeostasis modulating epithelium–macrophage interactions.

Language: Английский

Citations

35