Increased Inflammatory Low-Density Neutrophils in Morbid Obesity: Gene Expression and Effect of Bariatric Surgery
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ABSTRACT:
PROVIDER: PRJNA675351 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13005731_1.fastq.gz | Fastqsanger.gz | |||
| SRR13005731_2.fastq.gz | Fastqsanger.gz | |||
| SRR13005732_1.fastq.gz | Fastqsanger.gz | |||
| SRR13005732_2.fastq.gz | Fastqsanger.gz | |||
| SRR13005733_1.fastq.gz | Fastqsanger.gz |
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Project description:Background: Low-density neutrophils (LDN) are increased in several inflammatory diseases, and may also play a role in low-grade chronic inflammation in obesity. Yet their role in obesity or the effect of bariatric surgery-induced weight loss is unknown. Methods: We compared circulating LDN, their function, and gene expression between morbidly obese patients (MOP; BMI > 40 Kg/m2) and normal-weight controls (NWC; BMI < 25 Kg/m2) in a case-control study. Additionally, in a prospective longitudinal study, we measure changes in the frequency of LDN before and after bariatric surgery, and tested possible associations with metabolic and inflammatory parameters. Findings: LDN and inflammatory markers were significantly increased in MOP (n=27) compared to NWC (n=20). Transcriptome analysis of LDN from MOP showed an increased neutrophil-related gene expression signature associated with inflammation, neutrophil activation, and immunosuppressive function. However, LDN did not suppress T cells proliferation and produced low levels of ROS. Circulating LDN in MOP significantly decreased after surgery in parallel with BMI, metabolic syndrome and inflammatory markers. Interpretation: Obesity increases LDN with inflammatory gene signature. Bariatric surgery has anti-inflammatory effect including reduction of LDN. Gene expression and phenotype suggest that LDN represent a neutrophil subset that may be associated with obesity-associated chronic inflammation that promotes co-morbidities.
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Project description:Bariatric surgery Targeted loci environmental
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Project description:Bariatric (or metabolic) surgery is the most effective treatment for severe obesity, resulting in sustained weight loss and rapid improvement in metabolic outcomes. However, it is currently unknown what molecular changes are induced by the surgery, how they relate to the health improvements, how early they occur, and whether they are maintained over time. In this study, we characterized early gene expression changes following surgery in blood samples from the “Personalised Medicine for Morbid Obesity” cohort. We observed widespread changes in gene expression only a few days after surgery. Pathways related to immune response were affected, in particular with a decreased expression of the NF-κB pathway and neutrophil cytotoxic activity genes, suggesting a reduction of the inflammatory state typically associated with obesity. Metabolic signaling was also affected, with decreased expression of genes from pathways related to glucagon and insulin secretion, and key regulators such as the appetite-controlling hormone ghrelin. Comparisons to publicly available transcriptomics datasets showed that beyond these specific changes, bariatric surgery induces a transcriptome-wide reversal of expression changes associated with obesity and with forms of type 2 diabetes related to obesity. Comparisons to transcriptomics studies with longer-term follow-ups after bariatric surgery showed that a large fraction of early-induced expression changes likely persist for several months. Taken together, we show that previously unreported early changes in blood gene expression after bariatric surgery provide in-depth insights into the resolution of the chronic inflammation associated with severe obesity and its connection with metabolic improvement.
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Project description:Bariatric surgery is associated with improved breast cancer (BC) outcomes, including greater immunotherapy effectiveness in a pre-clinical BC model. A potential mechanism of bariatric surgery-associated protection is through the gut microbiota. Here, we demonstrate the dependency of improved immunotherapy response on the post-bariatric surgery gut microbiome via fecal microbial transplant. Cecal contents were isolated from either obese controls that received sham surgery or formerly obese mice following bariatric surgery-induced weight loss and transferred by FMT to lean recipients. Response to αPD-1 immunotherapy was significantly improved following FMT from formerly obese bariatric-surgery treated mice. Microbes can impact tumor burden through microbially derived metabolites produced or modified by gut microbiota including branched chain amino acids (BCAA). Circulating BCAA correlated significantly with NK T cell content in the tumor microenvironment in both donor mice after bariatric surgery and in FMT recipients of donor cecal content after bariatric surgery compared to obese sham controls. Findings implicate a role of microbially-derived BCAA in activating anti-tumor immunity that is dependent upon bariatric surgery. Importantly, when stool from a patient who exhibited 25% weight loss post-bariatric surgery was transplanted into recipient mice and compared to the patient’s pre-bariatric surgery stool transplant. Patient samples post bariatric surgery significantly reduced tumor burden by 2.4-fold and immunotherapy effectiveness was doubled. Taken together, findings suggest that reinvigorating anti-tumor immunity may be dependent upon microbially derived metabolites such as BCAA.
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Project description:Projection of gut microbiome pre and post bariatric surgery to predict surgery outcome
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Project description:A prospective, multicenter, cohort study was conducted in patients with severe obesity, who were randomized between two bariatric surgery techniques (Roux-en-Y gastric bypass and one anastomosis gastric bypass). Fecal samples were collected from 45 obese patients before surgery (T0) and 24 months after surgery (T1) and analyzed by shotgun metaproteomics.
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Project description:Effect of bariatric surgery on microbiome composition and microbial metabolomics.
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Project description:The Metagenome in Bariatric Surgery
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Project description:The molecular background of mitochondrial dysfunction in adipose tissue of morbidly obese individuals and bariatric surgery-induced changes in adipose mitochondrial function remain incompletely understood. To evaluate the mechanisms behind the surgery-induced changes and differences between morbidly obese subjects and nonobese controls, we performed a LC-MS/MS proteomics analysis of abdominal subcutaneous (SAT) and visceral adipose tissue samples (VAT) collected from the bariatric surgery, SAT samples collected 6 months after surgery, and control SAT and VAT samples collected from baseline.
2025-01-30 | PXD034182 | Pride
Project description:Adipose tissue before and after bariatric surgery (BPD/DS)-Pilot study using AB1700 microarrays. Subcutaneous abdominal adipose tissue pre and post bariatric surgery (BPD/DS).
2010-06-10 | E-TABM-864 | biostudies-arrayexpress