ABSTRACT
Osmotic diarrhea is a prevalent condition in humans caused by food intolerance, malabsorption, and widespread laxative use. Here, we assess the resilience of the gut ecosystem to osmotic perturbation at multiple length and timescales using mice as model hosts. Osmotic stress caused reproducible extinction of highly abundant taxa and expansion of less prevalent members in human and mouse microbiotas. Quantitative imaging revealed decimation of the mucus barrier during osmotic perturbation, followed by recovery. The immune system exhibited temporary changes in cytokine levels and a lasting IgG response against commensal bacteria. Increased osmolality prevented growth of commensal strains in vitro, revealing one mechanism contributing to extinction. Environmental availability of microbiota members mitigated extinction events, demonstrating how species reintroduction can affect community resilience. Our findings (1) demonstrate that even mild osmotic diarrhea can cause lasting changes to the microbiota and host and (2) lay the foundation for interventions that increase system-wide resilience.
Subject(s)
Diarrhea/pathology , Gastrointestinal Microbiome/drug effects , Polyethylene Glycols/pharmacology , Animals , Bacteroidetes/drug effects , Bacteroidetes/genetics , Bacteroidetes/isolation & purification , Cecum/chemistry , Cecum/metabolism , Cecum/microbiology , Cecum/pathology , Colon/chemistry , Colon/microbiology , Colon/pathology , Cytokines/metabolism , Diarrhea/immunology , Diarrhea/microbiology , Diarrhea/veterinary , Feces/microbiology , Glycoside Hydrolases/metabolism , Humans , Immunity, Humoral/drug effects , Immunoglobulin G/metabolism , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Metagenomics , Mice , Osmolar Concentration , Polyethylene Glycols/metabolism , Proteome/analysis , RNA, Ribosomal, 16S/chemistry , RNA, Ribosomal, 16S/genetics , Verrucomicrobia/drug effects , Verrucomicrobia/genetics , Verrucomicrobia/isolation & purificationABSTRACT
In recognition of the rising incidence and mortality of cancer in low- and middle-resource settings, as well as the increasingly international profile of its membership, ASCO has prioritized efforts to enhance its engagement at a global level. Among the recommendations included in the 2016 Global Oncology Leadership Task Force report to the ASCO Board of Directors was that ASCO should promote the recognition of global oncology as an academic field. The report suggested that ASCO could serve a role in transitioning global oncology from an informal field of largely voluntary activities to a more formal discipline with strong research and well-defined training components. As a result of this recommendation, in 2017, ASCO formed the Academic Global Oncology Task Force (AGOTF) to guide ASCO's contributions toward formalizing the field of global oncology. The AGOTF was asked to collect and analyze key issues and barriers toward the recognition of global oncology as an academic discipline, with an emphasis on training, research, and career pathways, and produce a set of recommendations for ASCO action. The outcome of the AGOTF was the development of recommendations designed to advance the status of global oncology as an academic discipline.