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A data integration multi-omics approach to study calorie restriction-induced changes in insulin sensitivity

ABSTRACT: The mechanisms responsible for weight loss-induced improvement in insulin sensitivity are partially understood. Greater insight can now be achieved through deep phenotyping and data integration. Here, we used an integrative approach to investigate associations between changes in insulin sensitivity and variations in lifestyle factors (diet and physical activity), subcutaneous adipose tissue (sAT) gene expression, metabolomics in serum, urine and feces, and gut microbiota composition after a 6-week calorie restriction period in overweight and obese adults. A spectrum of variables from lifestyle factors, gut microbiota and host multi-omics most associated with insulin sensitivity was identified. These analyses highlight associations between variations in insulin sensitivity, serum branched chain amino acids, sAT genes involved in endoplasmic reticulum stress and ubiquitination, and gut metagenomic species. This work has enhanced previous knowledge on mechanistic links between host glucose homeostasis, lifestyle factors and microbiota, and has identified modifiable factors and biomarkers that may be used to predict and improve individual response to weight loss interventions.

INSTRUMENT(S): Gas Chromatography MS - Positive (GC-MS (Positive))

PROVIDER: MTBLS653 | MetaboLights | 2021-02-11

REPOSITORIES: MetaboLights

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A Data Integration Multi-Omics Approach to Study Calorie Restriction-Induced Changes in Insulin Sensitivity.

Dao Maria Carlota MC Sokolovska Nataliya N Brazeilles Rémi R Affeldt Séverine S Pelloux Véronique V Prifti Edi E Chilloux Julien J Verger Eric O EO Kayser Brandon D BD Aron-Wisnewsky Judith J Ichou Farid F Pujos-Guillot Estelle E Hoyles Lesley L Juste Catherine C Doré Joël J Dumas Marc-Emmanuel ME Rizkalla Salwa W SW Holmes Bridget A BA Zucker Jean-Daniel JD Clément Karine K

Frontiers in physiology 20190205

<b>Background:</b> The mechanisms responsible for calorie restriction (CR)-induced improvement in insulin sensitivity (IS) have not been fully elucidated. Greater insight can be achieved through deep biological phenotyping of subjects undergoing CR, and integration of big data. <b>Materials and Methods:</b> An integrative approach was applied to investigate associations between change in IS and factors from host, microbiota, and lifestyle after a 6-week CR period in 27 overweight or obese adults ...[more]

PMID: 30804813

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Project description:Aims Gut microbiota-mediated inflammation promotes obesity-associated low-grade inflammation, which represents a hallmark of the metabolic syndrome (MetS). Lifestyle-induced weight loss (WL) is regarded as an efficient therapy to reverse MetS and to prevent disease progression. The objective of this study was to investigate if lifestyle-induced WL modulates the gut microbiome and its interaction with the host. Methods We analyzed and compared the fecal metaproteome of 33 individuals with MetS in a longitudinal study before and after lifestyle-induced WL in a well-defined cohort (ICTRP Trial Number: U1111-1158-3672). Results The 6-month WL intervention resulted in reduced BMI (-13.9%), increased insulin sensitivity (HOMA-IR; -53.70%) and reduced levels of circulating CRP (-66.86%), indicating MetS reversal. The metaprotein spectra of the host revealed a decrease of human proteins associated with gut inflammation and reduced abundance of human pancreatic alpha-amylase. Surprisingly, taxonomic analysis of the fecal metaproteome revealed only minor changes in the bacterial composition with an increase of low-abundant families (Desulfovibrionaceae, Leptospiraceae, Syntrophomonadaceae, Thermotogaceae, Verrucomicrobiaceae). Yet, we detected increased abundance of microbial metaprotein spectra that correspond to enhanced hydrolysis of complex carbohydrates (endoglucanase A, β-1,4-mannooligosaccharide phosphorylase, galactokinase, 5-keto-D-gluconate 5-reductase), indicating functional changes of the gut microbiome. Conclusions Our results indicate that lifestyle induced WL may improve interaction between the gut microbiome and the host in individuals with MetS, while bacterial composition remained almost stable. Metaproteome analysis of host proteins reveals reduced gut inflammation whereas microbial metaprotein spectra indicate functional changes towards degradation of complex carbohydrates. The filenames correspond to the ID of the patient (1-33), whereas “C” corresponds to baseline and “ABC” to weight loss.

			Action	DRS
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	PARIS_TMS_S15S6.mzML	Mzml
	PARIS_TMS_S17J0.mzML	Mzml
	PARIS_TMS_S17S6.mzML	Mzml
	PARIS_TMS_S1J0.mzML	Mzml