Gut microbiota modulate CD8+ T cell immunity in gastric cancer through Butyrate/GPR109A/HOPX

From BugSigDB
Reviewed Marked as Reviewed by KateRasheed on 2025-6-6
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Yu X, Ou J, Wang L, Li Z, Ren Y, Xie L, Chen Z, Liang J, Shen G, Zou Z, Zhao C, Li G, Hu Y
Journal
Gut microbes
Year
2024
Keywords:
CD8+ T cell immunity, Gut microbiota, butyrate, gastric cancer
The gut microbiota and Short-chain fatty acids (SCFAs) can influence the progression of diseases, yet the role of these factors on gastric cancer (GC) remains uncertain. In this work, the analysis of the gut microbiota composition and SCFA content in the blood and feces of both healthy individuals and GC patients indicated that significant reductions in the abundance of intestinal bacteria involved in SCFA production were observed in GC patients compared with the controls. ABX mice transplanted with fecal microbiota from GC patients developed more tumors during the induction of GC and had lower levels of butyric acid. Supplementation of butyrate during the induction of gastric cancer along with H. pylori and N-methyl-N-nitrosourea (MNU) in WT in GPR109A-/-mice resulted in fewer tumors and more IFN-γ+ CD8+ T cells, but this effect was significantly weakened after knockout of GPR109A. Furthermore, In vitro GC cells and co-cultured CD8+ T cells or CAR-Claudin 18.2+ CD8+ T cells, as well as in vivo tumor-bearing studies, have indicated that butyrate enhanced the killing function of CD8+ T cells or CAR-Claudin 18.2+ CD8+ T cells against GC cells through G protein-coupled receptor 109A (GPR109A) and homologous domain protein homologous box (HOPX). Together, these data highlighted that the restoration of gut microbial butyrate enhanced CD8+ T cell cytotoxicity via GPR109A/HOPX, thus inhibiting GC carcinogenesis, which suggests a novel theoretical foundation for GC management against GC.

Experiment 1


Reviewed Marked as Reviewed by KateRasheed on 2025-6-6

Curated date: 2025/05/06

Curator: MyleeeA

Revision editor(s): MyleeeA

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Gastric cancer Ca body - stomach,ca greater curvature of stomach,Ca lesser curvature - stomach,cancer of stomach,gastric cancer,gastric cancer, intestinal,gastric neoplasm,malignant gastric neoplasm,malignant gastric tumor,malignant neoplasm of body of stomach,malignant neoplasm of lesser curve of stomach,malignant neoplasm of stomach,malignant neoplasm of the stomach,malignant stomach neoplasm,malignant tumor of body of stomach,malignant tumor of greater curve of stomach,malignant tumor of lesser curve of stomach,malignant tumor of stomach,malignant tumor of the stomach,stomach cancer,Gastric cancer
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normal Individuals (N)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Gastric Cancer patients (GC)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients admitted to the hospital with Gastric cancer.
Group 0 sample size Number of subjects in the control (unexposed) group
20
Group 1 sample size Number of subjects in the case (exposed) group
20
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 months

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
LEfSe
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2

Alpha Diversity

Simpson Estimator of species richness and species evenness: more weight on species evenness
decreased

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-6

Curated date: 2025/05/06

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 1A, Supplementary Figure 2A and Supplementary Figure 3A

Description: Differential analysis of microbial community composition between Gastric Cancer-patients (GC) and Normal Individuals (N).

Abundance in Group 1: increased abundance in Gastric Cancer patients (GC)

NCBI Quality ControlLinks
Acidovorax
Akkermansia
Akkermansiaceae
Bacilli
Chloroflexota
Clostridium
Lactobacillaceae
Lactobacillales
Limosilactobacillus
Morganella
Morganella morganii
Morganellaceae
Peptostreptococcus
Rothia
Streptococcaceae
Streptococcus
Streptococcus mitis
Streptococcus parasanguinis
Streptococcus sp.
Verrucomicrobiales
Verrucomicrobiia
Verrucomicrobiota
[Ruminococcus] torques
unclassified Acidovorax
unclassified Akkermansia
unclassified Clostridia
unclassified Limosilactobacillus
unclassified Peptostreptococcus
unclassified Streptococcus
unclassified Tannerellaceae
uncultured Streptococcus sp.
Burkholderia Caballeronia ParaburkholderiaBurkholderia Caballeronia Paraburkholderia
Burkholderia Caballeronia Paraburkholderia UnclassifiedBurkholderia Caballeronia Paraburkholderia Unclassified

Revision editor(s): MyleeeA

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-6-6

Curated date: 2025/05/06

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Figure 1A, Supplementary Figure 2A and Supplementary Figure 3A

Description: Differential analysis of microbial community composition between Gastric Cancer-patients (GC) and Normal Individuals (N).

Abundance in Group 1: decreased abundance in Gastric Cancer patients (GC)

NCBI Quality ControlLinks
Agathobacter
Anaerostipes
Bacteria
Bacteria incertae sedis
Butyricicoccaceae
Butyricicoccus
Catenibacterium
Clostridia
Clostridiaceae
Clostridium
Coprobacillaceae
Coprococcus
Dorea
Eubacteriales
Faecalibacterium
Fusicatenibacter
Fusobacteriaceae
Fusobacteriales
Fusobacteriia
Fusobacteriota
Fusobacterium
Lachnoclostridium
Lachnoclostridium edouardi
Lachnospira
Lachnospira eligens
Lachnospiraceae
Lachnospirales
Monoglobaceae
Monoglobales
Monoglobus
Muribaculaceae
Oscillospiraceae
Peptostreptococcaceae
Phascolarctobacterium
Romboutsia
Roseburia
Roseburia faecis
Ruminococcus
Subdoligranulum
[Ruminococcus] torques
unclassified Agathobacter
unclassified Anaerostipes
unclassified Bacillota
unclassified Butyricicoccus
unclassified Catenibacterium
unclassified Dorea
unclassified Faecalibacterium
unclassified Fusicatenibacter
unclassified Fusobacterium
unclassified Lachnoclostridium
unclassified Lachnospira
unclassified Monoglobus
unclassified Muribaculaceae
unclassified Papillibacter
unclassified Romboutsia
unclassified Roseburia
unclassified Ruminococcus
unclassified Subdoligranulum
Erysipelotrichaceae UCG-003Erysipelotrichaceae UCG-003
Peptostreptococcaceae TissierellalesPeptostreptococcaceae Tissierellales
Erysipelotrichaceae UCG-003 UnclassifiedErysipelotrichaceae UCG-003 Unclassified
Ruminococcus torques group UnclassifiedRuminococcus torques group Unclassified
Eubacterium eligens group UnclassifiedEubacterium eligens group Unclassified
Unclassified Clostridium senso stricto 1Unclassified Clostridium senso stricto 1

Revision editor(s): MyleeeA

Experiment 2


Reviewed Marked as Reviewed by KateRasheed on 2025-6-6

Curated date: 2025/05/06

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Host species Species from which microbiome was sampled. Contact us to have more species added.
Mus musculus
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Response to transplant Response to transplant,response to transplant
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normal-Fecal Microbiota Transplant (F-N)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Gastric Cancer-Fecal Microbiota Transplant (F-CA)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Mice given Antibiotic (ABX) and transplanted with Gastric Cancer microbiota (F-CA) from human.
Group 0 sample size Number of subjects in the control (unexposed) group
6
Group 1 sample size Number of subjects in the case (exposed) group
6
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Not specified

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-6-6

Curated date: 2025/05/06

Curator: MyleeeA

Revision editor(s): MyleeeA, Anne-mariesharp

Source: Figure 2H and Supplementary Figure 9A

Description: Differential analysis of microbial community composition between Gastric Cancer-Fecal Microbiota Transplant (F-CA) and Normal-Fecal Microbiota Transplant (F-N).

Abundance in Group 1: increased abundance in Gastric Cancer-Fecal Microbiota Transplant (F-CA)

NCBI Quality ControlLinks
Actinomyces
Actinomycetaceae
Actinomycetales
Akkermansia
Akkermansiaceae
Bacteroides sp. XB44A
Blautia
Blautia sp.
Candidatus Methylomirabilia
Candidatus Methylomirabilota
Clostridium sp. Clone-7
Mycoplasmataceae
Mycoplasmatales
Turicibacter
Verrucomicrobiales
Verrucomicrobiia
Verrucomicrobiota
unclassified Actinomyces
unclassified Akkermansia
unclassified Cetobacterium
unclassified Desulfovibrionaceae
unclassified Mycoplasmataceae
unclassified Romboutsia
unclassified Turicibacter
Rokubacteriales UnclassifiedRokubacteriales Unclassified
RokubacterialesRokubacteriales
unclassified Anaerovoracaceae Incertae Sedis

Revision editor(s): MyleeeA, Anne-mariesharp

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-6-6

Curated date: 2025/05/06

Curator: MyleeeA

Revision editor(s): MyleeeA, Anne-mariesharp

Source: Figure 2H and Supplementary Figure 9A

Description: Differential analysis of microbial community composition between Gastric Cancer-Fecal Microbiota Transplant (F-CA) and Normal-Fecal Microbiota Transplant (F-N).

Abundance in Group 1: decreased abundance in Gastric Cancer-Fecal Microbiota Transplant (F-CA)

NCBI Quality ControlLinks
Acetatifactor sp.
Anaerotignum
Anaerotignum sp.
Bacteria incertae sedis
Bilophila
Bittarella (ex Durand et al. 2017)
Bittarella massiliensis (ex Durand et al. 2017)
Butyricicoccaceae
Butyricicoccus
Chthonobacter
Clostridia
Colidextribacter
Desulfovibrionaceae
Desulfovibrionales
Desulfovibrionia
Eubacteriaceae
Eubacteriales
Eubacterium
Gaiella
Gaiellaceae
Intestinimonas
Intrasporangiaceae
Lachnospiraceae
Lachnospiraceae bacterium NK4A136
Lachnospirales
Oscillibacter sp.
Oscillospiraceae
Paludibacter propionicigenes
Pantoea agglomerans
Paramuribaculum
Paramuribaculum intestinale
Peptococcaceae
Phocaeicola paurosaccharolyticus
Pleomorphomonadaceae
Pseudaeromonas
Pseudaeromonas sharmana
Thermodesulfobacteriota
unclassified Bilophila
unclassified Butyricicoccus
unclassified Chthonobacter
unclassified Colidextribacter
unclassified Eubacteriales
unclassified Gaiella
unclassified Harryflintia
unclassified Intestinimonas
unclassified Ktedonobacteria
unclassified Lachnospiraceae
unclassified Oscillibacter
unclassified Oscillospiraceae
unclassified Peptococcaceae
uncultured Bacteroides sp.
uncultured Clostridium sp.
uncultured Eubacterium sp.
Eubacterium xylanophilum group unclassifiedEubacterium xylanophilum group unclassified
Unclassified Prevotellaceae UCG-001Unclassified Prevotellaceae UCG-001
Lachnospiraceae FCS020 group UnclassifiedLachnospiraceae FCS020 group Unclassified
Lachnospiraceae NK4A136 group UnclassifiedLachnospiraceae NK4A136 group Unclassified
Prevotellaceae UCG-001Prevotellaceae UCG-001
Incertae sedis UnclassifiedIncertae sedis Unclassified
PeptococcalesPeptococcales
MB A2 108 UnclassifiedMB A2 108 Unclassified
MB A2 108MB A2 108
Lachnospiraceae FCS020 groupLachnospiraceae FCS020 group
Lachnospiraceae UCG 010 UnclassifiedLachnospiraceae UCG 010 Unclassified
Lachnospiraceae UCG 010Lachnospiraceae UCG 010
KF JG30 C25 UnclassifiedKF JG30 C25 Unclassified
KF JG30 C25KF JG30 C25
GCA900066575 UnclassifiedGCA900066575 Unclassified
Parabacteroides provencensis
Eubacterium xylanophilum

Revision editor(s): MyleeeA, Anne-mariesharp

Experiment 3


Reviewed Marked as Reviewed by KateRasheed on 2025-7-29

Curated date: 2025/05/06

Curator: MyleeeA

Revision editor(s): MyleeeA

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Gastric juice Stomach secretion,Succus gastricus,Gastric juice,gastric juice
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normal mouse (N)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Gastric Cancer Mouse (Ca)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Gastric cancer mouse- 20 g C57BL/6J mi­ce at 6 weeks of age infec­ted with Helicobacter pylori and given N-methyl-N-nitrosourea (MNU) plus abnormal feeding cycles, to induce gastric cancer.
Group 0 sample size Number of subjects in the control (unexposed) group
4
Group 1 sample size Number of subjects in the case (exposed) group
5

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by KateRasheed on 2025-7-29

Curated date: 2025/05/06

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Supplementary Figure 4A

Description: Differential analysis of microbial community composition of gastric fluids between Gastric Cancer mouse and Normal mouse.

Abundance in Group 1: increased abundance in Gastric Cancer Mouse (Ca)

NCBI Quality ControlLinks
Alistipes
Anaerotruncus
Bacteria incertae sedis
Bacteroides
Clostridium
Colidextribacter
Helicobacter
Mucispirillum
Muribaculum
Oscillibacter
Parabacteroides
Tyzzerella
bacterium A2
unclassified Bacteroidota
unclassified Eubacteriales
unclassified Lachnospiraceae
unclassified Oscillospiraceae
Rikenellaceae RC9 gut groupRikenellaceae RC9 gut group
Clostridia vadinBB60 group UnclassifiedClostridia vadinBB60 group Unclassified
UnclassifiedUnclassified
TuzzerellaTuzzerella
Lachnospiraceae FCS020 groupLachnospiraceae FCS020 group
Family XIII UCG-001Family XIII UCG-001
uncultured Clostridium sp.

Revision editor(s): MyleeeA

Signature 2

Reviewed Marked as Reviewed by KateRasheed on 2025-7-29

Curated date: 2025/05/06

Curator: MyleeeA

Revision editor(s): MyleeeA

Source: Supplementary Figure 4A

Description: Differential analysis of microbial community composition of gastric fluids between Gastric Cancer mouse and Normal mouse.

Abundance in Group 1: decreased abundance in Gastric Cancer Mouse (Ca)

NCBI Quality ControlLinks
Dubosiella
Ligilactobacillus
Methyloversatilis
Pseudomonas
Vibrio

Revision editor(s): MyleeeA