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The gut microbiome enhances breast cancer immunotherapy following bariatric surgery

ABSTRACT: The gut microbiome enhances breast cancer immunotherapy following bariatric surgery

PROVIDER: PRJNA1231419 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32565546_1.fastq.gz	Fastqsanger.gz
	SRR32565546_2.fastq.gz	Fastqsanger.gz
	SRR32565547_1.fastq.gz	Fastqsanger.gz
	SRR32565547_2.fastq.gz	Fastqsanger.gz
	SRR32565548_1.fastq.gz	Fastqsanger.gz

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The gut microbiome enhances breast cancer immunotherapy following bariatric surgery

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.

2025-04-14 | GSE291031 | GEO

Bariatric surgery reduces obesity associated breast cancer and enhances response to immunotherapy

Project description:Bariatric surgery reduces obesity associated breast cancer and enhances response to immunotherapy

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Bariatric surgery reduces obesity associated breast cancer and enhances response to immunotherapy [Tumor - breast cancer RNA-seq]

Project description:Patients undergoing bariatric surgery are protected from subsequent breast cancer risk. It is unknown whether weight loss alone or surgery-specific alterations mediate risk reduction. We examined breast cancer in a pre-clinical model of diet induced obesity (DIO) followed by vertical sleeve gastrectomy (VSG) or dietary weight loss. DIO exacerbated tumor progression compared to lean controls, while VSG-induced weight loss reversed this exacerbation. However, dietary interventions were more effective than VSG despite similar reductions in weight and adiposity, potentially due to elevated immunosuppression after VSG. In tumor bearing mice, anti-PD-L1 immunotherapy after VSG improved anti-tumor immunity and potently impaired tumor progression. Thus, weight loss before tumor onset was protective regardless of intervention. Importantly, immunotherapy specifically improved outcomes in VSG.

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Bariatric surgery reduces obesity associated breast cancer and enhances response to immunotherapy [Mammary Fat Pad RNA-seq]

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Project description:Bariatric surgery Targeted loci environmental

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Oral microbiome change in Obese following bariatric surgery

Project description:Oral microbiome change in Obese following bariatric surgery

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Rapid and long-lasting remodelling of the blood transcriptome following bariatric surgery

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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