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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
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.
| Study ID | ST003790 |
| Study Title | Fecal 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 Summary | Immune 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 Name | Roichman |
| First Name | Asael |
| Address | Lewis-Sigler Institute for Integrative Genomics Princeton University Carl Icahn Laboratory, Washington Road Princeton, NJ 08544 |
| asael100@gmail.com | |
| Phone | 9084101710 |
| Submit Date | 2025-03-11 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzXML |
| Analysis Type Detail | LC-MS |
| Release Date | 2025-03-31 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002366 |
| Project DOI: | doi: 10.21228/M8SZ6Z |
| Project Title: | Lack of consistent effect of dietary fiber on immune checkpoint blockade efficacy across diverse murine tumor models |
| Project Summary: | Immune 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 Name: | Roichman |
| First Name: | Asael |
| Address: | Lewis-Sigler Institute for Integrative Genomics Princeton University Carl Icahn Laboratory, Washington Road Princeton, NJ 08544 |
| Email: | asael100@gmail.com |
| Phone: | 9084101710 |
| Publications: | Lack of consistent effect of dietary fiber on immune checkpoint blockade efficacy across diverse murine tumor models |
Subject:
| Subject ID: | SU003924 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Genotype Strain: | WT C57BL/6J (Jax #000664) |
| Gender: | Female |
| Animal Feed: | Chow or low and high-fiber purified diets |
| Animal Water: | RO water |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Sample source | Diet | Treatment |
|---|---|---|---|---|
| SA412545 | blank2 | blank | blank | blank |
| SA412546 | blank1 | blank | blank | blank |
| SA412509 | 59 | Feces | Chow | anti-PD-1 |
| SA412510 | 64 | Feces | Chow | anti-PD-1 |
| SA412511 | 63 | Feces | Chow | anti-PD-1 |
| SA412512 | 61 | Feces | Chow | anti-PD-1 |
| SA412513 | 60 | Feces | Chow | anti-PD-1 |
| SA412514 | 62 | Feces | Chow | anti-PD-1 |
| SA412515 | 56 | Feces | Chow | isotype control |
| SA412516 | 55 | Feces | Chow | isotype control |
| SA412517 | 54 | Feces | Chow | isotype control |
| SA412518 | 53 | Feces | Chow | isotype control |
| SA412519 | 52 | Feces | Chow | isotype control |
| SA412520 | 51 | Feces | Chow | isotype control |
| SA412521 | 76 | Feces | HC_In0 | anti-PD-1 |
| SA412522 | 78 | Feces | HC_In0 | anti-PD-1 |
| SA412523 | 77 | Feces | HC_In0 | anti-PD-1 |
| SA412524 | 73 | Feces | HC_In0 | anti-PD-1 |
| SA412525 | 74 | Feces | HC_In0 | anti-PD-1 |
| SA412526 | 75 | Feces | HC_In0 | anti-PD-1 |
| SA412527 | 85 | Feces | HC_In1.9 | anti-PD-1 |
| SA412528 | 84 | Feces | HC_In1.9 | anti-PD-1 |
| SA412529 | 83 | Feces | HC_In1.9 | anti-PD-1 |
| SA412530 | 82 | Feces | HC_In1.9 | anti-PD-1 |
| SA412531 | 86 | Feces | HC_In1.9 | anti-PD-1 |
| SA412532 | 87 | Feces | HC_In1.9 | anti-PD-1 |
| SA412533 | 89 | Feces | HC_In8 | anti-PD-1 |
| SA412534 | 90 | Feces | HC_In8 | anti-PD-1 |
| SA412535 | 92 | Feces | HC_In8 | anti-PD-1 |
| SA412536 | 93 | Feces | HC_In8 | anti-PD-1 |
| SA412537 | 95 | Feces | HC_In8 | anti-PD-1 |
| SA412538 | 94 | Feces | HC_In8 | anti-PD-1 |
| SA412539 | 72 | Feces | LC_In0 | anti-PD-1 |
| SA412540 | 71 | Feces | LC_In0 | anti-PD-1 |
| SA412541 | 68 | Feces | LC_In0 | anti-PD-1 |
| SA412542 | 67 | Feces | LC_In0 | anti-PD-1 |
| SA412543 | 66 | Feces | LC_In0 | anti-PD-1 |
| SA412544 | 65 | Feces | LC_In0 | anti-PD-1 |
| Showing results 1 to 38 of 38 |
Collection:
| Collection ID: | CO003917 |
| Collection Summary: | Feces were collected from ad lib fed mice around 9am, the day after the sixth dose of anti-PD-1 or isotype control. Samples were stored at -80°C until further processing. |
| Sample Type: | Feces |
| Storage Conditions: | -80℃ |
Treatment:
| Treatment ID: | TR003933 |
| Treatment Summary: | Mice were randomized and assigned to treatment groups when the average tumor volume reached 40-100 mm3. Mice were dosed with 100ug of anti-PD-1 (BE0273, clone 29F.1A12, BioXcell) or isotype control (BE0089, Rat IgG2a, BioXcell). This was administered as a 100 µl intraperitoneal injection, diluted in InVivoPure pH 7.0 Dilution Buffer (IP0070, BioXcell) for Anti-PD-1 or InVivoPure pH 6.5 Dilution Buffer (IP0065, BioXcell) for the IgG2a isotype control. Mice were dosed every 3 days for a total of 8 doses. |
Sample Preparation:
| Sampleprep ID: | SP003930 |
| Sampleprep Summary: | Frozen feces samples were transferred to Eppendorf tubes with ceramic beads on dry ice and disrupted by cryomill (Retsch). About 10 mg of homogenized powder was weighed and extracted by ice-cold acetonitrile: methanol: water (40:40:20, supplemented with 0.5 % vol formic acid). Extracts were vortexed for 10 s, kept on dry ice for 10 min, and neutralized by NH4HCO3 (15% in water, 8.8% vol/vol of extraction buffer was used). Neutralized extracts were vortexed for 10 s again, kept on dry ice for 1h, and centrifuged at 21, 380 g, 4°C for 20 min. Supernatants were collected for LC-MS analysis. |
Combined analysis:
| Analysis ID | AN006230 | AN006231 |
|---|---|---|
| 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 |
MS:
| MS ID: | MS005934 |
| Analysis ID: | AN006230 |
| Instrument Name: | Thermo Orbitrap Exploris 480 |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | MS analysis was performed on Thermo Fisher’s Orbitrap Exploris 480 mass spectrometer, with injection volume of 5-10 µL. Two scans were performed, in negative mode (m/z of 70-1000) and positive mode (m/z of 119-1000), respectively, with resolution of 120,000, AGC target of 1000% and max injection time of 500 ms. |
| Ion Mode: | NEGATIVE |
| MS ID: | MS005935 |
| Analysis ID: | AN006231 |
| Instrument Name: | Thermo Orbitrap Exploris 480 |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | MS analysis was performed on Thermo Fisher’s Orbitrap Exploris 480 mass spectrometer, with injection volume of 5-10 µL. Two scans were performed, in negative mode (m/z of 70-1000) and positive mode (m/z of 119-1000), respectively, with resolution of 120,000, AGC target of 1000% and max injection time of 500 ms. |
| Ion Mode: | POSITIVE |
