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Systematic Metaproteomic Mapping of Ex vivo Gut Microbiota Functional Responses to Therapeutic Drugs (2)

ABSTRACT: Some therapeutic compounds can influence our gut microbiota, but a comprehensive understanding of their impact on microbial systems ecology remains largely unexplored. This study examines the impact of 312 therapeutic compounds on metaproteomes of six ex vivo human gut microbiota, generating 4.6 million microbial protein responses, available as an interactive resource. Further data analysis discovered that 15% of the compounds induced consistent functional changes across microbiotas, with neuropharmaceuticals being significantly enriched. These neuropharmaceuticals induced profound metaproteomic alterations, along with community-level functional redundancy (FR) decrease and antimicrobial resistance protein (ARP) increase. Two functional states in the metaproteomic response landscape were observed: one with high FR and low ARP, and another with decreased FR and induced ARP. Based on the energy landscape principle, we validated that enhancing FR maintained a microbiota’s resilience against neuropharmaceutical-induced ARP increase. Our results highlight a novel strategy to counter drug-induced negative impacts by leveraging the functional landscape.

INSTRUMENT(S):

ORGANISM(S): Human Gut Metagenome

TISSUE(S): Feces

SUBMITTER: Leyuan Li

LAB HEAD: Daniel Figeys

PROVIDER: PXD056930 | Pride | 2025-08-28

REPOSITORIES: Pride

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			Action	DRS
	Leyuan_20220330_300drugs_V45_P1A11.raw	Raw
	Leyuan_20220330_300drugs_V45_P1A2.raw	Raw
	Leyuan_20220330_300drugs_V45_P1A7.raw	Raw
	Leyuan_20220330_300drugs_V45_P1A8.raw	Raw
	Leyuan_20220330_300drugs_V45_P1A9.raw	Raw

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Systematic Metaproteomic Mapping of Ex vivo Gut Microbiota Functional Responses to Therapeutic Drugs (1)

Project description:Some therapeutic compounds can influence our gut microbiota, but a comprehensive understanding of their impact on microbial systems ecology remains largely unexplored. This study examines the impact of 312 therapeutic compounds on metaproteomes of six ex vivo human gut microbiota, generating 4.6 million microbial protein responses, available as an interactive resource. Further data analysis discovered that 15% of the compounds induced consistent functional changes across microbiotas, with neuropharmaceuticals being significantly enriched. These neuropharmaceuticals induced profound metaproteomic alterations, along with community-level functional redundancy (FR) decrease and antimicrobial resistance protein (ARP) increase. Two functional states in the metaproteomic response landscape were observed: one with high FR and low ARP, and another with decreased FR and induced ARP. Based on the energy landscape principle, we validated that enhancing FR maintained a microbiota’s resilience against neuropharmaceutical-induced ARP increase. Our results highlight a novel strategy to counter drug-induced negative impacts by leveraging the functional landscape.

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