Summary of Study ST003790

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002366. The data can be accessed directly via it's Project DOI: 10.21228/M8SZ6Z This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST003790
Study TitleFecal metabolomics of B16-OVA tumor-bearing mice fed chow or low and high fiber purified diets and treated with isotype control or anti-PD-1 antibody
Study SummaryImmune checkpoint blockade (ICB) has transformed cancer treatment, but success rates remain limited. Recent research suggests dietary fiber enhances ICB response in mice and patients through microbiome-dependent mechanisms. Yet, the robustness of this effect across cancer types and dietary contexts remains unclear. Specifically, prior literature compared grain-based chow (high fiber) to low-fiber purified diet, but these diets differ also on other dimensions including phytochemicals. Here we investigated, in mice fed grain-based chow or purified diets with differing quantities of isolated fibers (cellulose and inulin), the gut microbiome, metabolite levels and ICB activity in multiple tumor models. Isolated fibers shifted multiple microbial taxa toward chow-like levels, although diet-type (chow vs. purified) had a stronger impact on gut-microbiome composition. Metabolomic profiles were relatively similar between mice fed high- and low-fiber purified diets, but differed massively between mice fed purified diets or chow, identifying the factor as diet type, independent of fiber. Tumor growth studies in multiple murine models revealed that fiber has a weaker impact on ICB (anti-PD-1) efficacy than previously reported. While diet impacted ICB activity in some models, the effect was not directionally consistent. In no model did we observe the pattern expected if fiber controlled ICB efficacy: strong efficacy in both chow and high-fiber purified diet but low efficacy in low-fiber purified diet. Thus, dietary fiber appears to have limited or inconsistent effect on ICB efficacy in mouse models, and other dietary factors that correlate with fiber intake may underlie the clinical correlations between fiber consumption and immunotherapy outcomes.
Institute
Princeton University
Last NameRoichman
First NameAsael
AddressLewis-Sigler Institute for Integrative Genomics Princeton University Carl Icahn Laboratory, Washington Road Princeton, NJ 08544
Emailasael100@gmail.com
Phone9084101710
Submit Date2025-03-11
Raw Data AvailableYes
Raw Data File Type(s)mzXML
Analysis Type DetailLC-MS
Release Date2025-03-31
Release Version1
Asael Roichman Asael Roichman
https://dx.doi.org/10.21228/M8SZ6Z
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN006230 AN006231
Chromatography ID CH004724 CH004724
MS ID MS005934 MS005935
Analysis type MS MS
Chromatography type HILIC HILIC
Chromatography system Thermo Vanquish Thermo Vanquish
Column Waters XBridge BEH Amide (150 x 2.1 mm, 2.5 μm) (SKU#: 186006724) Waters XBridge BEH Amide (150 x 2.1 mm, 2.5 μm) (SKU#: 186006724)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Orbitrap Exploris 480 Thermo Orbitrap Exploris 480
Ion Mode NEGATIVE POSITIVE
Units Ion intensity Ion intensity

Chromatography:

Chromatography ID:CH004724
Chromatography Summary:Metabolites were separated by hydrophilic interaction liquid chromatography (HILIC) with an XBridge BEH Amide column (2.1 mm × 150 mm, 2.5 μm particle size; Waters, 196006724). The column temperature was set at 25°C. Solvent A was 95 vol% H2O 5 vol% acetonitrile (with 20 mM ammonium acetate, 20 mM ammonium hydroxide, pH 9.4). Solvent B was acetonitrile. Flow rate was 0.15 mL/min. The LC gradient was: 0-2min, 90% B; 3-7min, 75% B; 8-9 min, 70% B; 10-12 min, 50% B; 13-14 min, 25% B; 16-20.5 min, 0.5% B; 21-25 min, 90%.
Instrument Name:Thermo Vanquish
Column Name:Waters XBridge BEH Amide (150 x 2.1 mm, 2.5 μm) (SKU#: 186006724)
Column Temperature:25°C
Flow Gradient:0-2min, 90% B; 3-7min, 75% B; 8-9 min, 70% B; 10-12 min, 50% B; 13-14 min, 25% B; 16-20.5 min, 0.5% B; 21-25 min, 90%.
Flow Rate:0.15 mL/min
Solvent A:95% Water/5% Acetonitrile; 20 mM Ammonium acetate; 20 mM Ammonium hydroxide (pH 9.4)
Solvent B:100% Acetonitrile
Chromatography Type:HILIC
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