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.

Ballanti, M., Antonetti, L., Mavilio, M., Casagrande, V., Moscatelli, A., Pietrucci, D., et al. (2024). Decreased circulating IPA levels identify subjects with metabolic comorbidities: A multi-omics study. PHARMACOLOGICAL RESEARCH, 204 [10.1016/j.phrs.2024.107207].

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

Ballanti, Marta
Membro del Collaboration Group
;
Antonetti, Lorenzo
Membro del Collaboration Group
;
Mavilio, Maria;Casagrande, Viviana;Moscatelli, Alessandro;Pietrucci, Daniele;Teofani, Adelaide;Cardellini, Marina;Monteleone, Giovanni;Menghini, Rossella;Federici, Massimo
2024-06-01

Abstract

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.
giu-2024
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/09
English
Con Impact Factor ISI
Cross-omics
Data integration
Diabetes
Diagnostic
Genomics
Gut
Hyperglycaemia
IPA
Next-generation metabolic screening
Next-generation sequencing
Untargeted metabolomics
Ballanti, M., Antonetti, L., Mavilio, M., Casagrande, V., Moscatelli, A., Pietrucci, D., et al. (2024). Decreased circulating IPA levels identify subjects with metabolic comorbidities: A multi-omics study. PHARMACOLOGICAL RESEARCH, 204 [10.1016/j.phrs.2024.107207].
Ballanti, M; Antonetti, L; Mavilio, M; Casagrande, V; Moscatelli, A; Pietrucci, D; Teofani, A; Internò, C; Cardellini, M; Paoluzi, O; Monteleone, G; ...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/379283
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