Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis

The composition of the intestinal microbiota influences the development of inflammatory disorders. However, associating inflammatory diseases with specific microbial members of the microbiota is challenging, because clinically detectable inflammation and its treatment can alter the microbiota’s comp...

Full description

Saved in:
Bibliographic Details
Published in:Nature communications Vol. 7; no. 1; p. 10391
Main Authors: Dubin, Krista, Callahan, Margaret K., Ren, Boyu, Khanin, Raya, Viale, Agnes, Ling, Lilan, No, Daniel, Gobourne, Asia, Littmann, Eric, Huttenhower, Curtis, Pamer, Eric G., Wolchok, Jedd D.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 02.02.2016
Nature Publishing Group
Nature Portfolio
Subjects:
631/326/2565/2134
692/699/1503/1581/1392/1388
692/699/67/1059/2325
692/699/67/1813/1634
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal - adverse effects
Bacteroidaceae
Bacteroidetes - genetics
Bacteroidetes - isolation & purification
Biosynthesis
Colitis - chemically induced
Colitis - microbiology
Female
Gastrointestinal Microbiome - genetics
Humanities and Social Sciences
Humans
Immunotherapy
Ipilimumab
Lymphocytes
Male
Melanoma
Melanoma - drug therapy
Melanoma - secondary
Middle Aged
multidisciplinary
Prospective Studies
Risk Factors
RNA, Ribosomal, 16S - genetics
Science
Science (multidisciplinary)
Sequence Analysis, RNA
Skin Neoplasms - drug therapy
Skin Neoplasms - pathology
ISSN:2041-1723, 2041-1723
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The composition of the intestinal microbiota influences the development of inflammatory disorders. However, associating inflammatory diseases with specific microbial members of the microbiota is challenging, because clinically detectable inflammation and its treatment can alter the microbiota’s composition. Immunologic checkpoint blockade with ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) signalling, is associated with new-onset, immune-mediated colitis. Here we conduct a prospective study of patients with metastatic melanoma undergoing ipilimumab treatment and correlate the pre-inflammation faecal microbiota and microbiome composition with subsequent colitis development. We demonstrate that increased representation of bacteria belonging to the Bacteroidetes phylum is correlated with resistance to the development of checkpoint-blockade-induced colitis. Furthermore, a paucity of genetic pathways involved in polyamine transport and B vitamin biosynthesis is associated with an increased risk of colitis. Identification of these biomarkers may enable interventions to reduce the risk of inflammatory complications following cancer immunotherapy. A subset of cancer patients treated with immune checkpoint blockade develops colitis. Here the authors show that lower abundance of Bacteroidetes and vitamin B biosynthetic modules in fecal samples of melanoma patients can predict their susceptibility to colitis following anti-CTLA-4 treatment.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
content type line 14
ObjectType-Feature-2
content type line 23
These authors jointly supervised this work.
ISSN:2041-1723
2041-1723
DOI:10.1038/ncomms10391