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MRNA Seq of mouse tissues 9 weeks after RYGB or sham surgery [9 weeks]

ABSTRACT: mRNA Seq of mouse tissues 9 weeks after RYGB or sham surgery [9 weeks]

PROVIDER: PRJNA454676 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7093420.fastq.gz	Fastqsanger.gz
	SRR7093430.fastq.gz	Fastqsanger.gz
	SRR7093440.fastq.gz	Fastqsanger.gz
	SRR7093450.fastq.gz	Fastqsanger.gz
	SRR7093460.fastq.gz	Fastqsanger.gz

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mRNA Seq of mouse tissues 9 weeks after RYGB or sham surgery [9 weeks]

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Project description:Objective: Roux-Y gastric bypass (RYGB) surgery is a last treatment resort to induce substantial and sustained weight loss in severe obesity. The anatomical rearrangement affects the intestinal microbiota but so far, little information is available how it interferes with microbial functionality and microbial-host interaction independent from weight loss. Design: A RYGB rat model was utilized and compared to sham-operated controls which were kept at matched body weight as RYGB animals by food restriction. We assessed microbial taxonomy by 16S rRNA gene sequencing and functional activity by metaproteomics and metabolomics on microbiota samples collected separately from the ileum, the cecum as well as the colon and separately analysed the lumen and mucus associated microbiota. Results: Altered gut architecture in RYGB strongly affected the occurrence of Actinobacteria, especially Bifidobacteriaceae and Proteobacteria which were increased, whereas Firmicutes were decreased, although Streptococcaceae and Clostridium perfringens were observed at higher abundances. A decrease of conjugated as well as secondary bile acids was observed in the RYGB-gut lumen. In addition the arginine biosynthesis pathway in the microbiota was altered, indicated by the changes in abundance of upstream metabolites and enzymes, resulting in lower levels of arginine and higher levels of aspartate in the colon after RYGB. Conclusion: The anatomical rearrangement in RYGB affects microbiota composition and functionality by changes in amino acid and bile acid metabolism, independent of weight loss. The shift in microbiota taxonomic structure after RYGB may be mediated by the resulting change in composition of the bile acid pool in the gut lumen.

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Project description:Roux-en-Y gastric bypass (RYGB) surgery reduces weight in obese patients. A marked decrease in blood glucose levels occurs before weight loss; however, key molecules that improve glycemic profile remain largely unknown. We used the RYGB surgery model in diet-induced obese (DIO) mice to monitor the proteome (with tandem mass tagging) of the Roux and biliopancreatic limbs, the liver and the pancreas up to four weeks after surgery, a time window associated with the early beneficial metabolic effects of the RYGB surgery model. The resulting kinetics were analyzed using high-dimensional cluster analysis that we recently developed (XINA,PMID: 30370770) to infer co-regulated proteins and pathways based on common kinetic profiles. Our analysis revealed the organs exhibited unique and common changes to their proteomes reflecting their specialized physiological roles and potential coordinated inter-organ crosstalk and responses, respectively. Further exploration of the Roux limb proteome kinetics included the identification of relatively unknown proteins found with clusters comprising established protein-protein interaction networks. One such protein was insulin-like growth factor binding protein 7 (Igfbp7) whose subsequent in vitro and in vivo studies supported the role of this secreted protein in suppressing hepatic gluconeogenesis; which in turn, substantiates our systems approach to discover new mechanisms by which the RYGB surgery exerts beneficial effects.

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