Dataset Information

Ena-DATASET-MDACC-02-02-2018-10:54:47:473-560 - samples

ABSTRACT: The oral and gut microbiomes of melanoma patients were characterized before the initiation of ant-PD1 immunotherapy, and compared to treatment response. Validation studies were performed in germ-free mice using stool from patients who responded/did not respond to ant-PD1 immunotherapy. All baseline oral(n=86) and gut (n=43) microbiome samples were subject to 16S sequencing - V4 region ( merged fastq files have been made available through this portal). Whole genome shotgun sequencing (WGS) was performed on a subset of fecal samples (n=25)- these files are also available( paired end reads). Also available are 16S sequencing results of stool samples from donors (n=2) used in fecal microbiota transplant and murine samples (n=12) from germ-free mice transplanted with stool from responder/non-responder patients.

PROVIDER: EGAD00001003943 | EGA |

REPOSITORIES: EGA

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Publications

Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.

Gopalakrishnan V V Spencer C N CN Nezi L L Reuben A A Andrews M C MC Karpinets T V TV Prieto P A PA Vicente D D Hoffman K K Wei S C SC Cogdill A P AP Zhao L L Hudgens C W CW Hutchinson D S DS Manzo T T Petaccia de Macedo M M Cotechini T T Kumar T T Chen W S WS Reddy S M SM Szczepaniak Sloane R R Galloway-Pena J J Jiang H H Chen P L PL Shpall E J EJ Rezvani K K Alousi A M AM Chemaly R F RF Shelburne S S Vence L M LM Okhuysen P C PC Jensen V B VB Swennes A G AG McAllister F F Marcelo Riquelme Sanchez E E Zhang Y Y Le Chatelier E E Zitvogel L L Pons N N Austin-Breneman J L JL Haydu L E LE Burton E M EM Gardner J M JM Sirmans E E Hu J J Lazar A J AJ Tsujikawa T T Diab A A Tawbi H H Glitza I C IC Hwu W J WJ Patel S P SP Woodman S E SE Amaria R N RN Davies M A MA Gershenwald J E JE Hwu P P Lee J E JE Zhang J J Coussens L M LM Cooper Z A ZA Futreal P A PA Daniel C R CR Ajami N J NJ Petrosino J F JF Tetzlaff M T MT Sharma P P Allison J P JP Jenq R R RR Wargo J A JA

Science (New York, N.Y.) 20171102 6371

Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (<i>n</i> = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patien ...[more]

PMID: 29097493

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Project description:Purpose: To determine whether previously observed behavioral differences in alcoholic human patients after fecal microbiota transplantation (FMT) could be transferred to mice. Methods: Fecal microbiota samples from a previously published phase 1, double-blind, randomized clinical trial of AUD-related cirrhosis patients were used to colonize germ-free mice. Fecal material was transferred to 10-15-week-old GF C57BL/6 male mice by daily gavage for 3 day. The mice were housed in sterile individually filtered cages for 15 days after which stool was collected and then they underwent the alcohol preference experiment using 2-bottle choice drinking (water and 20% ethanol v/v). Microbial DNA was isolated from stool samples by sequencing the V1 and V2 variable regions of the bacterial 16S rRNA gene were sequenced using Multitag fusion primers and sequenced on an Ion Torrent PGM next-generation sequencer. Intestinal mucosa, liver, and prefrontal cortex tissue was collected from mice at time of sacrifice. RNAseq was used to measure gene expression in pre-FMT and post-FMT samples. RNAseq data were aligned to the mouse genome (GRCm39) using STAR (version 2.7.9a) and counts were generated with HTSeq (version 0.13.5). Genes with very low counts across the study (defined as fewer than 10 counts in more than 2 samples) were eliminated before differential expression analysis. Low count genes were determined separately for each tissue type. The DESeq2 package for R was then used to measure differential expression between pre-FMT and post-FMT mice in the intestine, liver, and PFC. Benjamini and Hochberg False Discovery Rate (FDR) was used to correct for multiple testing with FDR ≤ 0.2 considered significant. Results: Mice colonized with post-FMT stool significantly reduced ethanol acceptance, intake and preference versus pre-FMT colonized mice. Microbial taxa that were higher in post-FMT humans were also associated with lower alcohol intake and preference in mice. RNAseq further showed that differential gene expression, post-FMT, occurred in the intestine rather than the liver and prefrontal cortex. Conclusions: FMT leads to significant change in gut microbiome population, which in turn alters gene expression in the intestine. FMT also significantly affects alcohol consumption. The microbiotal-intestinal interface may alter gut-liver-brain axis and reduce alcohol consumption in humans.

Dataset Information

Ena-DATASET-MDACC-02-02-2018-10:54:47:473-560 - samples

Publications

Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.

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