Obesity has repeatedly been linked to reorganization of the gut microbiome, yet to this point obesity therapeutics have been targeted exclusively toward the human host. Here, we show that gut microbe-targeted inhibition of the trimethylamine N-oxide (TMAO) pathway protects mice against the metabolic disturbances associated with diet-induced obesity (DIO) or leptin deficiency (). Small molecule inhibition of the gut microbial enzyme choline TMA-lyase (CutC) does not reduce food intake but is instead associated with alterations in the gut microbiome, improvement in glucose tolerance, and enhanced energy expenditure. We also show that gut microbial CutC inhibition is associated with reorganization of host circadian control of both phosphatidylcholine and energy metabolism. This study underscores the relationship between microbe and host metabolism and provides evidence that gut microbe-derived trimethylamine (TMA) is a key regulator of the host circadian clock. This work also demonstrates that gut microbe-targeted enzyme inhibitors have potential as anti-obesity therapeutics.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8813054PMC
http://dx.doi.org/10.7554/eLife.63998DOI Listing

Publication Analysis

Top Keywords

gut microbe-targeted
12
host circadian
12
gut
8
gut microbiome
8
gut microbial
8
host
5
microbe-targeted choline
4
choline trimethylamine
4
trimethylamine lyase
4
inhibition
4

Similar Publications

Decoding the Gut Microbiome in Companion Animals: Impacts and Innovations.

Microorganisms

September 2024

TREE Lab, Department of Biomedical and Life Sciences, School of Science, Navrachana University, Vadodara 391410, India.

Article Synopsis
  • The evolving perception of companion animals emphasizes their importance as family members and highlights the link between gut microbiota and overall health in these animals.
  • The review discusses diseases related to gut microbiome changes, including inflammatory bowel disease and obesity, and examines factors that influence gut microbiome composition like age and diet.
  • It also covers detection methods for studying gut microbiota, noting their limitations, and suggests future research directions for understanding microbial interactions related to animal health.
View Article and Find Full Text PDF

Machine learning for data integration in human gut microbiome.

Microb Cell Fact

November 2022

Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.

Recent studies have demonstrated that gut microbiota plays critical roles in various human diseases. High-throughput technology has been widely applied to characterize the microbial ecosystems, which led to an explosion of different types of molecular profiling data, such as metagenomics, metatranscriptomics and metabolomics. For analysis of such data, machine learning algorithms have shown to be useful for identifying key molecular signatures, discovering potential patient stratifications, and particularly for generating models that can accurately predict phenotypes.

View Article and Find Full Text PDF

Bacterial Species Associated With Human Inflammatory Bowel Disease and Their Pathogenic Mechanisms.

Front Microbiol

February 2022

Gastrointestinal and Liver Unit, Prince of Wales Hospital, University of New South Wales, Sydney, NSW, Australia.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with unknown etiology. The pathogenesis of IBD results from immune responses to microbes in the gastrointestinal tract. Various bacterial species that are associated with human IBD have been identified.

View Article and Find Full Text PDF

Obesity has repeatedly been linked to reorganization of the gut microbiome, yet to this point obesity therapeutics have been targeted exclusively toward the human host. Here, we show that gut microbe-targeted inhibition of the trimethylamine N-oxide (TMAO) pathway protects mice against the metabolic disturbances associated with diet-induced obesity (DIO) or leptin deficiency (). Small molecule inhibition of the gut microbial enzyme choline TMA-lyase (CutC) does not reduce food intake but is instead associated with alterations in the gut microbiome, improvement in glucose tolerance, and enhanced energy expenditure.

View Article and Find Full Text PDF

What Is Known about Theragnostic Strategies in Colorectal Cancer.

Biomedicines

February 2021

Department of Biotechnology and Applied Clinical Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

Despite the paradigmatic shift occurred in recent years for defined molecular subtypes in the metastatic setting treatment, colorectal cancer (CRC) still remains an incurable disease in most of the cases. Therefore, there is an urgent need for new tools and biomarkers for both early tumor diagnosis and to improve personalized treatment. Thus, liquid biopsy has emerged as a minimally invasive tool that is capable of detecting genomic alterations from primary or metastatic tumors, allowing the prognostic stratification of patients, the detection of the minimal residual disease after surgical or systemic treatments, the monitoring of therapeutic response, and the development of resistance, establishing an opportunity for early intervention before imaging detection or worsening of clinical symptoms.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!