Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chemotherapy Modulation by a Cancer-Associated Microbiota Metabolite

ABSTRACT: The microbiota plays a major role in cancer. How the microbiota interacts with nutrients to produce regulatory metabolites is of significance for cancer therapy. Using a host-microbe-drug-nutrient 4-way screening approach, we evaluated the role of nutrition at the molecular level in the context of 5-fluorouracil toxicity. Notably, we identified the metabolite 2-methylisocitrate to be produced and enriched in human tumor-associated microbiomes. 2-methylisocitrate exhibits anti-proliferative properties across genetically- and tissue-diverse cancer cell lines, 3D spheroids, and an in vivo Drosophila gut tumor model, where it reduced tumor dissemination and increased survival. Drug-metabolite screening traced the chemotherapeutic signatures indicating synergy between 5-fluorouracil and 2-methylisocitrate, and multi-omic analyses revealed that 2-methylisocitrate acts via multiple cellular pathways linking metabolism and DNA damage to regulate chemotherapy. Finally, building on nature’s template, we altered the chemical structure of 2-methylisocitrate, enhancing its potency. This work highlights the great impact of microbiome-derived metabolites on tumor proliferation, and their potential as promising co-adjuvants for cancer treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE263706 | GEO | 2025/09/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

RNA-seq of Ctrl and NaBu-treated CD8+ T cells in vitro

Project description:Recent studies in both mice and human have suggested that the gut microbiota could modulate tumor response to chemotherapeutic agents or immunotherapies. However, the underlying mechanism has not been well characterized. Here, we found that disruption of the intestinal microbiota with antibiotics impaired the anti-cancer efficacy of oxaliplatin, which was correlated with the reduction of lots of the intestinal microbial metabolites including butyrate, one of the short chain fatty acids. Re-supplementation of either the whole intestinal microbial metabolites or butyrate could rescue the therapeutic responses of oxaliplatin in the microbiota-destroyed tumor-bearing mice by modulating CD8+ T cell function in the tumor microenvironment. Further experiments showed butyrate boosted the anti-tumor cytotoxic CD8+ T cell responses through ID2, a key transcription regulator highly expressed by tumor-infiltrating CD8+ T cells. Butyrate induced ID2 expression in CD8+ T cells, while ID2 further promoted the proliferation and function of CD8+ T cells through IL-12 signaling. Together, our findings suggest that gut microbial metabolite butyrate could promote the anti-tumor therapeutic efficacy through the ID2-dependent regulation of CD8+ T cell immunity.

2021-03-24 | GSE115426 | GEO

RNA-seq of WT and ID2KO CD8+ T cells in iLN of tumor-bearing mice after oxaliplatin treatment

2021-03-24 | GSE115283 | GEO

Metabolic Drug Response Phenotyping in Colorectal Cancer Organoids by LC-QTOF-MS

Project description:As metabolic rewiring is crucial for cancer cell proliferation, metabolic phenotyping of patient-derived organoids is desirable to identify drug-induced changes and trace metabolic vulnerabilities of tumor subtypes. We established a novel protocol for metabolomic and lipidomic profiling of colorectal cancer organoids by LC-QTOF-MS facing the challenge of capturing metabolic information from minimal sample amount (< 500 cells/injection) in the presence of extracellular matrix (ECM). The best procedure of the tested protocols included ultrasonic metabolite extraction with acetonitrile/methanol/water (2:2:1, v/v/v) without ECM removal. To eliminate ECM-derived background signals, we implemented a data filtering procedure based on p-value and fold change cut-offs which retained features with signal intensities >120% compared to matrix-derived signals present in blank samples. As a proof-of-concept, the method was applied to examine the early metabolic response of colorectal cancer organoids to 5-fluorouracil treatment. Statistical analysis revealed dose-dependent changes in the metabolic profiles of treated organoids including elevated levels of 2'-deoxyuridine, 2'-O-methylcytidin, inosine and 1-methyladenosine and depletion of 2'-deoxyadenosine and specific phospholipids. In accordance with the mechanism of action of 5-fluorouracil, changed metabolites are mainly involved in purine and pyrimidine metabolism. The novel protocol provides a first basis for the assessment of metabolic drug response phenotypes in 3D organoid models.

2021-10-12 | MTBLS2130 | MetaboLights

F. nucleatum-derived succinic acid induces tumor resistance to immunotherapy in colorectal cancer

Project description:At present, the mechanisms underlying the association between gut microbiota metabolites and immunotherapy in CRC remain unknown. Here, we conducted a multiomics analysis of a cohort of patients with mCRC and found that F.nucleatum was more abundant in patients who did not respond to immunotherapy. We also found that F. nucleatum diminished the sensitivity to anti-PD-1 mAb through its metabolite succinic acid. Accordingly, patients with lower serum succinic acid levels achieved a better response to immunotherapy. Mechanistically, F.nucleatum-derived succinic acid suppressed the cGAS-interferon-β pathway, consequently dampening the antitumor response by limiting CD8+ T-cell trafficking to the tumor microenvironment in vivo. Treatment with metronidazole reduced intestinal F.nucleatum abundance and thereby decreased serum succinic acid levels, thus resensitizing the tumors to immunotherapy in vivo. Collectively, our findings indicate that F. nucleatum and its metabolite succinic acid induce tumor resistance to immunotherapy and offer new insights into microbiota-metabolite-immune crosstalk in CRC.

2023-10-01 | GSE181337 | GEO

F. nucleatum-derived succinic acid induces tumor resistance to immunotherapy in colorectal cancer

2023-12-01 | GSE209864 | GEO

Reuterin in the healthy gut microbiome suppresses colorectal cancer growth through altering redox balance

Project description:Microbial dysbiosis is a colorectal cancer (CRC) hallmark and contributes to inflammation, tumor growth, and therapy response. Gut microbes signal via metabolites, but how the metabolites impact CRC is largely unknown. We interrogated fecal metabolites associated with mouse models of colon tumorigenesis with varying mutational load. We found that microbial metabolites from healthy mice or humans were growth-repressive, and this response was attenuated in mice and patients with CRC. Microbial profiling revealed that Lactobacillus reuteri and its metabolite, reuterin were downregulated in mouse and human CRC. Reuterin altered redox balance, and reduced survival, and proliferation in colon cancer cells. Reuterin induced selective protein oxidation, and inhibited ribosomal biogenesis and protein translation. Exogenous Lactobacillus reuteri restricted mouse colon tumor growth, increased tumor reactive oxygen species, and decreased protein translation in vivo. Our findings indicate that a healthy microbiome and specifically, Lactobacillus reuteri, is protective against CRC through microbial metabolite exchange.

2021-12-12 | GSE186880 | GEO

Microbiota-derived Inosine Suppresses Systemic Autoimmunity via Restriction of B Cell Differentiation and Migration

Project description:The role of gut microbiota dysbiosis in systemic lupus erythematosus (SLE) pathogenesis remains elusive. Here, we show that fecal microbiota transplantation (FMT) from healthy mice to lupus mice ameliorated lupus-like symptoms. Microbiota reconstitution effectively reduced systemic class switch recombination and elevated IGH naïve isotype. Microbiota profiling revealed an enrichment of Lactobacillus johnsonii post-FMT, with a significant correlation to purine metabolites. Importantly, the Lactobacillus johnsonii-derived inosine, an intermediate metabolite in purine metabolism, effectively alleviated lupus-like symptoms by impeding B cell differentiation and reducing renal B cell infiltration. We further demonstrated that inosine reprograms B cells through the ERK-HIF-1α signaling pathway. Overall, our study highlights the discovery of a novel microbial metabolite modulating autoimmunity and suggests its potential for innovative microbiome-based therapeutic approaches.

2024-03-31 | GSE255441 | GEO

Gut microbe-derived metabolites drive psoriatic inflammation via modulation of skin Th17 cells

Project description:The maintenance of tissue-specific chronic inflammation results from the interplay of genetic and unidentified environmental factors. Here, we describe an immunoregulatory role for an environmentally driven microbial metabolite in Card14E138A/+-induced spontaneous psoriasis. Through metabolite screening, we demonstrate chronic skin inflammation is accompanied by alterations microbial metabolite. Notably, depletion of gut, not skin, microbes alleviates disease symptoms. We further identify indoxyl sulfate (I3S), a bacteriogenic metabolite, as a key driver of psoriatic inflammation and confirm that gut-resident indole-producing microbiota mediate this process. Mechanistically, indole-producing microbiota promote host I3S biothsynthesis via a metabolic relay, and I3S potentiates skin inflammation by reshaping chromatin accessibility in skin Th17 cells through AHR signaling. In human psoriasis cohorts, serum I3S levels correlate with disease severit. In summary, our study uncovers a mechanistic link between gut microbial factors and type 3 skin inflammation, highlighting targeting gut microbiota as a strategy for mitigating skin inflammation.

2025-08-22 | GSE298131 | GEO

Gut microbe-derived metabolites drive psoriatic inflammation via modulation of skin Th17 cells

2025-07-02 | GSE298540 | GEO

Chronic stress dampens Lactobacillus johnsonii-driven suppression on cancer stemness and enhances colorectal tumorigenicity

Project description:More than one-half of all colorectal cancer cases and deaths are due to modifiable risk factors, while psychological stress stands out as an important factor with mechanism unclear. Polymorphic microbiomes have pivotal roles in CRC. We therefore explored the impact of chronic stress on CRC, and the involvement of gut microbiome and its metabolites in this process.

2023-12-20 | GSE210896 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data