Gut microbiota-derived gamma-aminobutyric acid improves host appetite by inhibiting satiety hormone secretion

Study information

Reviewed Marked as Reviewed by Svetlana up on 2024-10-26

study design

laboratory experiment

Citation

PMID PubMed identifier for scientific articles.

39315776

DOI Digital object identifier for electronic documents.

10.1128/msystems.01015-24

URI

Authors

Li S, Liu M, Han Y, Liu C, Cao S, Cui Y, Zhu X, Wang Z, Liu B, Shi Y

Journal

mSystems

Year

2024

Keywords:

appetite hormones, feeding regulation, gamma-aminobutyric acid, microbiota-gut-brain axis

Globally, appetite disorders have become an increasingly prominent public health issue. While short-term appetite loss may seem relatively harmless, prolonged instances can lead to serious physical and mental damage. In recent years, numerous studies have highlighted the significant role of the "microbiota-gut-brain" axis in the regulation of feeding behavior in organisms, suggesting that targeting the gut microbiota may be a novel therapeutic strategy for appetite disorders. However, the molecular mechanisms through which the gut microbiota mediates the increase in host appetite and the causal relationship between the two remain unclear. Based on this, we conducted 16S rRNA sequencing to analyze the gut microbiota of rabbits with high and low feed intake, followed by fecal microbiota transplantation (FMT) and metabolite gavage experiments to elucidate the underlying mechanisms. Our research indicates that the high feed intake group exhibited significant enrichment of the g__Bacteroides and gamma-aminobutyric acid (GABA), and intragastric administration of GABA effectively promoted the host's feeding behavior. The underlying mechanism involves GABA derived from the gut microbiota inhibiting the secretion of satiety hormones to enhance the host's feeding behavior. Furthermore, the results of FMT suggest that differences in gut microbiota composition may be a contributing factor to varying levels of feed intake in the host. In conclusion, these findings emphasize the role of the gut microbiota-derived GABA, in increasing host feed intake, offering a new target for the treatment of appetite disorders from the perspective of gut microbiota.IMPORTANCEThe incidence of anorexia is rapidly increasing and has become a global burden. Gut microbiota can participate in the regulation of host feeding behavior, yet the molecular mechanisms through which the gut microbiota mediates the increase in host appetite and the causal relationship between them remain unclear. In this study, we utilized 16S rRNA sequencing to investigate the composition of the gut microbiota in rabbits with varying levels of feed intake and employed fecal microbiota transplantation and gastric infusion experiments with gamma-aminobutyric acid (GABA) to elucidate the potential mechanisms involved. GABA derived from the gut microbiota can effectively enhance the host's feeding behavior by inhibiting the secretion of satiety hormones. This discovery underscores the pivotal role of the gut microbiota in modulating host appetite, offering novel research avenues and therapeutic targets for appetite disorders.

Experiment 1

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Reviewed Marked as Reviewed by Svetlana up on 2024-10-26

Curated date: 2024/10/13

Curator: YokoC

Revision editor(s): YokoC

Subjects

Location of subjects: China

Host species Species from which microbiome was sampled. Contact us to have more species added.: Oryctolagus cuniculus

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Material entity in digestive tract Digestive tract contents,Ingested material entity,Material entity in digestive tract,material entity in digestive tract

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Eating behaviour Eating behaviour,eating behaviour

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Low feed intake

Group 1 name Corresponds to the case (exposed) group for case-control studies: High feed intake

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: The six rabbits with the highest feed intake from a group of 100 rabbits.

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

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V1-V9

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: PacBio RS

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): 0.01

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: 3

Alpha Diversity

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

Chao1 Abundance-based estimator of species richness: unchanged

Signature 1

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Reviewed Marked as Reviewed by Svetlana up on 2024-10-26

Curated date: 2024/10/14

Curator: YokoC

Revision editor(s): YokoC, Scholastica

Source: Fig 4H

Description: Differences in gut microbiota at genus level between High Feed Intake and Low Feed Intake rabbit groups.

Abundance in Group 1: increased abundance in High feed intake

NCBI	Quality Control	Links
Bacteroides
Mediterranea
unclassified Actinomycetota
unclassified Coriobacteriia

Revision editor(s): YokoC, Scholastica

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Curated date: 2024/10/14

Curator: YokoC

Revision editor(s): YokoC, Rahila, Scholastica

Source: Fig 4H

Description: Differences in gut microbiota at genus level between High Feed Intake and Low Feed Intake rabbit groups.

Abundance in Group 1: decreased abundance in High feed intake

NCBI	Quality Control	Links
Acetivibrio
Breznakia
Spiroplasma
unclassified Erysipelotrichaceae
unclassified Gammaproteobacteria
unclassified Mollicutes
unclassified Oscillospiraceae

Revision editor(s): YokoC, Rahila, Scholastica

Experiment 2

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Curated date: 2024/10/18

Curator: YokoC

Revision editor(s): YokoC

Differences from previous experiment shown

Subjects

Lab analysis

Statistical Analysis

Statistical test: Mann-Whitney (Wilcoxon)

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: Not specified

Signature 1

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Reviewed Marked as Reviewed by Svetlana up on 2024-10-26

Curated date: 2024/10/18

Curator: YokoC

Revision editor(s): YokoC, Scholastica

Source: Fig 4G

Description: Differential analysis at species level in High Feed Intake versus Low Feed Intake rabbit groups.

Abundance in Group 1: increased abundance in High feed intake

NCBI	Quality Control	Links
Bacteroides caccae
Bacteroides rodentium

Revision editor(s): YokoC, Scholastica