Decreased circulating IPA levels identify subjects with metabolic comorbidities: A multi-omics study

In recent years several experimental observations demonstrated that the gut microbiome plays a role in regulating positively or negatively metabolic homeostasis. Indole-3-propionic acid (IPA), a Tryptophan catabolic product mainly produced by C. Sporogenes, has been recently shown to exert either fa...

Full description

Saved in:

Bibliographic Details
Published in:	Pharmacological research Vol. 204; p. 107207
Main Authors:	Ballanti, Marta, Antonetti, Lorenzo, Mavilio, Maria, Casagrande, Viviana, Moscatelli, Alessandro, Pietrucci, Daniele, Teofani, Adelaide, Internò, Chiara, Cardellini, Marina, Paoluzi, Omero, Monteleone, Giovanni, Lefebvre, Philippe, Staels, Bart, Mingrone, Geltrude, Menghini, Rossella, Federici, Massimo
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier Ltd 01-06-2024 Elsevier
Subjects:	Adult Animals Comorbidity Cross-omics Data integration Diabetes Diagnostic Female Gastrointestinal Microbiome Genomics Gut Humans Hyperglycaemia Indoles Insulin Resistance IPA Male Metabolic Syndrome - blood Metabolic Syndrome - metabolism Metabolic Syndrome - microbiology Metabolomics Mice Mice, Inbred C57BL Middle Aged Multiomics Muscle, Skeletal - metabolism Muscle, Skeletal - microbiology Next-generation metabolic screening Next-generation sequencing Untargeted metabolomics Hyperglycaemia Cross-omics Genomics HFD Gut highIPA Diagnostic Next-generation sequencing Next-generation metabolic screening Data integration lowIPA IPA Diabetes Untargeted metabolomics
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	In recent years several experimental observations demonstrated that the gut microbiome plays a role in regulating positively or negatively metabolic homeostasis. Indole-3-propionic acid (IPA), a Tryptophan catabolic product mainly produced by C. Sporogenes, has been recently shown to exert either favorable or unfavorable effects in the context of metabolic and cardiovascular diseases. We performed a study to delineate clinical and multiomics characteristics of human subjects characterized by low and high IPA levels. Subjects with low IPA blood levels showed insulin resistance, overweight, low-grade inflammation, and features of metabolic syndrome compared to those with high IPA. Metabolomics analysis revealed that IPA was negatively correlated with leucine, isoleucine, and valine metabolism. Transcriptomics analysis in colon tissue revealed the enrichment of several signaling, regulatory, and metabolic processes. Metagenomics revealed several OTU of ruminococcus, alistipes, blautia, butyrivibrio and akkermansia were significantly enriched in highIPA group while in lowIPA group Escherichia-Shigella, megasphera, and Desulfovibrio genus were more abundant. Next, we tested the hypothesis that treatment with IPA in a mouse model may recapitulate the observations of human subjects, at least in part. We found that a short treatment with IPA (4 days at 20/mg/kg) improved glucose tolerance and Akt phosphorylation in the skeletal muscle level, while regulating blood BCAA levels and gene expression in colon tissue, all consistent with results observed in human subjects stratified for IPA levels. Our results suggest that treatment with IPA may be considered a potential strategy to improve insulin resistance in subjects with dysbiosis. [Display omitted] •Low circulating IPA is correlated with insulin resistance and low-grade inflammation in human subjects.•IPA treatment ameliorates insulin resistance in mouse model of diet induced obesity.•IPA is potentially useful as an agent to improve metabolic homeostasis or as a biomarker in human subjects.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1043-6618 1096-1186
DOI:	10.1016/j.phrs.2024.107207