Dataset Information

The gut microbiome enhances breast cancer immunotherapy following bariatric surgery

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE291031 | GEO | 2025/04/14

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Obesity is associated with multiple diseases. Bariatric surgery is the most effective therapy for severe obesity that can reduce body weight and obesity-associated morbidity. The metabolic alterations associated with obesity and respective changes after bariatric surgery are incompletely understood.We comprehensively assessed metabolic alterations associated with severe obesity and distinct bariatric procedures. In our longitudinal observational study, we applied a (1)H-nuclear magnetic resonance-based global, untargeted metabolomics strategy on human serum samples that were collected before and repeatedly <=1 y after distinct bariatric procedures [i.e., a sleeve gastrectomy, proximal Roux-en Y gastric bypass (RYGB), and distal RYGB]. For comparison, we also analyzed serum samples from normal-weight and less-obese subjects who were matched for 1-y postoperative body mass index (BMI) values of the surgical groups. We identified a metabolomic fingerprint in obese subjects that was clearly discriminated from that of normal-weight subjects. Furthermore, we showed that bariatric surgery (sleeve gastrectomy and proximal and distal RYGB) dynamically affected this fingerprint in a procedure-dependent manner, thereby establishing new fingerprints that could be discriminated from those of BMI-matched and normal-weight control subjects. Metabolites that largely contributed to the metabolomic fingerprints of severe obesity were aromatic and branched-chain amino acids (elevated), metabolites related to energy metabolism (pyruvate and citrate; elevated), and metabolites suggested to be derived from gut microbiota (formate, methanol, and isopropanol; all elevated). Our data indicate that bariatric surgery, irrespective of the specific kind of procedure used, reverses most of the metabolic alterations associated with obesity and suggest profound changes in gut microbiome-host interactions after the surgery. This trial was registered at clinicaltrials.gov as NCT02480322.

Dataset Information

The gut microbiome enhances breast cancer immunotherapy following bariatric surgery

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets