Gut microbiome affects the response to anti-PD-1 immunotherapy in patients with hepatocellular carcinoma

Study information

Reviewed Marked as Reviewed by Fatima on 2022/09/7

study design

prospective cohort

Citation

PMID PubMed identifier for scientific articles.

31337439

DOI Digital object identifier for electronic documents.

10.1186/s40425-019-0650-9

URI

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651993/

Authors

Zheng Y, Wang T, Tu X, Huang Y, Zhang H, Tan D, Jiang W, Cai S, Zhao P, Song R, Li P, Qin N, Fang W

Journal

Journal for immunotherapy of cancer

Year

2019

Keywords:

Anti-PD-1 immunotherapy, Gut microbiome, Hepatocellular carcinoma

BACKGROUND: Checkpoint-blockade immunotherapy targeting programmed cell death protein 1 (PD-1) has recently shown promising efficacy in hepatocellular carcinoma (HCC). However, the factors affecting and predicting the response to anti-PD-1 immunotherapy in HCC are still unclear. Herein, we report the dynamic variation characteristics and specificities of the gut microbiome during anti-PD-1 immunotherapy in HCC using metagenomic sequencing. RESULTS: Fecal samples from patients responding to immunotherapy showed higher taxa richness and more gene counts than those of non-responders. For dynamic analysis during anti-PD-1 immunotherapy, the dissimilarity of beta diversity became prominent across patients as early as Week 6. In non-responders, Proteobacteria increased from Week 3, and became predominant at Week 12. Twenty responder-enriched species, including Akkermansia muciniphila and Ruminococcaceae spp., were further identified. The related functional genes and metabolic pathway analysis, such as carbohydrate metabolism and methanogenesis, verified the potential bioactivities of responder-enriched species. CONCLUSIONS: Gut microbiome may have a critical impact on the responses of HCC patients treated with anti-PD-1 immunotherapy. The dynamic variation characteristics of the gut microbiome may provide early predictions of the outcomes of immunotherapy in HCC, which is critical for disease-monitoring and treatment decision-making.

Experiment 1

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Reviewed Marked as Reviewed by Fatima on 2022/09/7

Curated date: 2022/09/03

Curator: Sharmilac

Revision editor(s): Sharmilac, Fatima

Subjects

Location of subjects: China

Host species Species from which microbiome was sampled (if applicable): 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

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: response to immunochemotherapy response to immunochemotherapy

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Non-responders
Group 1 name Corresponds to the case (exposed) group for case-control studies: Responders
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Responders (R, n = 3) were defined by radiographic evidence as complete or partial response, or stable disease lasting for at least six months.
Group 0 sample size Number of subjects in the control (unexposed) group: 5
Group 1 sample size Number of subjects in the case (exposed) group: 3

Lab analysis

Sequencing type: WMS

Not specified

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: BGISEQ-500 Sequencing

Statistical Analysis

Statistical test: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 2

Alpha Diversity

Richness Number of species: increased

Signature 1

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Reviewed Marked as Reviewed by Fatima on 2022/10/27

Curated date: 2022/09/03

Curator: Sharmilac

Revision editor(s): Sharmilac, Fatima

Source: text, Figure 2A, Figure S4

Description: Meta-analysis of the bacteria significantly enriched in R and NR. a Heatmap showing the relative abundance of R-enriched and NR-enriched bacterial species, as identified by LEfSe. Differentially abundant genera (a) and species (b) between R and NR, identified by LEfSe.

Abundance in Group 1: increased abundance in Responders

NCBI	Quality Control	Links
Akkermansia muciniphila
Anaerobutyricum hallii
Anaerotruncus colihominis
Bacteroides cellulosilyticus
Bifidobacterium dentium
Blautia obeum
Candidatus Liberibacter brunswickensis
Coprococcus comes
Dialister invisus
Dorea formicigenerans
Fusobacterium ulcerans
Lachnospiraceae bacterium 7_1_58FAA
Lactobacillus gasseri
Limosilactobacillus mucosae
Limosilactobacillus oris
Limosilactobacillus vaginalis
Megasphaera micronuciformis
Ruminococcus bromii
Salinibacter
Streptococcus thermophilus
Subdoligranulum
Lactobacillus
Bifidobacterium
unclassified Subdoligranulum
Ruminococcus
Akkermansia
Dialister
Scardovia

Revision editor(s): Sharmilac, Fatima

Signature 2

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Reviewed Marked as Reviewed by Fatima on 2022/10/27

Curated date: 2022/09/03

Curator: Sharmilac

Revision editor(s): Sharmilac, Fatima, Aiyshaaaa

Source: text, Figure 2A

Description: Meta-analysis of the bacteria significantly enriched in R and NR. a Heatmap showing the relative abundance of R-enriched and NR-enriched bacterial species, as identified by LEfSe.

Abundance in Group 1: decreased abundance in Responders

NCBI	Quality Control	Links
Aggregatibacter aphrophilus
Bacteroides eggerthii
Bacteroides fluxus
Bacteroides nordii
Bacteroides uniformis
Bartonella
Bifidobacterium adolescentis
Bifidobacterium bifidum
Bordetella
Escherichia albertii
Fusobacterium varium
Haemophilus pittmaniae
Klebsiella aerogenes
Ligilactobacillus salivarius
Megasphaera elsdenii
Turicibacter
Veillonella atypica
Veillonella dispar
unclassified Propionibacteriaceae
Cellvibrio

Revision editor(s): Sharmilac, Fatima, Aiyshaaaa