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Bariatric Surgery

ABSTRACT: Projection of gut microbiome pre and post bariatric surgery to predict surgery outcome

PROVIDER: PRJEB39382 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR4340970.fastq.gz	Fastqsanger.gz
	ERR4340980.fastq.gz	Fastqsanger.gz
	ERR4340990.fastq.gz	Fastqsanger.gz
	ERR4341000.fastq.gz	Fastqsanger.gz
	ERR4341010.fastq.gz	Fastqsanger.gz

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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:This study involved the collection of 25 (16 female and nine male adults) plasma samples from bariatric surgery patients. Plasma was prepared from blood samples taken pre-surgery (within 48 hours, files with the suffix ‘Pre’) and nine months post-surgery (files with the suffix ‘Post’).

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