Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis

Autor: Daniel van der Lelie, Bo Liu, Sarah D. Watson, Kun Lu, R. Balfour Sartor, Muyiwa Awoniyi, Christopher S. Henry, Junji Umeno, Lisa Ouellette, Akihiko Oka, Yunjia Lai, Liang Chi, Safiyh Taghavi, Katherine E. Merrell, Ting Jia Fan
Rok vydání: 2021
Předmět:
0301 basic medicine
medicine.medical_treatment
General Physics and Astronomy
Feces
Mice
fluids and secretions
0302 clinical medicine
Homeostasis
Intestinal Mucosa
Mice
Knockout
Multidisciplinary
digestive
oral
and skin physiology
Gastroenterology
food and beverages
Colitis
Cytokine
030220 oncology & carcinogenesis
Cytokines
medicine.symptom
Science
Inflammation
Microbiology
digestive system
Article
General Biochemistry
Genetics and Molecular Biology
Proinflammatory cytokine
Bile Acids and Salts
03 medical and health sciences
Immune system
Immunity
medicine
Animals
Germ-Free Life
Humans
Metabolomics
Microbiome
Bacteria
business.industry
General Chemistry
medicine.disease
digestive system diseases
Gastrointestinal Microbiome
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
Immunology
Dysbiosis
business
Zdroj: Nature Communications, Vol 12, Iss 1, Pp 1-17 (2021)
Nature Communications
ISSN: 2041-1723
Popis: Environmental factors, mucosal permeability and defective immunoregulation drive overactive immunity to a subset of resident intestinal bacteria that mediate multiple inflammatory conditions. GUT-103 and GUT-108, live biotherapeutic products rationally designed to complement missing or underrepresented functions in the dysbiotic microbiome of IBD patients, address upstream targets, rather than targeting a single cytokine to block downstream inflammation responses. GUT-103, composed of 17 strains that synergistically provide protective and sustained engraftment in the IBD inflammatory environment, prevented and treated chronic immune-mediated colitis. Therapeutic application of GUT-108 reversed established colitis in a humanized chronic T cell-mediated mouse model. It decreased pathobionts while expanding resident protective bacteria; produced metabolites promoting mucosal healing and immunoregulatory responses; decreased inflammatory cytokines and Th-1 and Th-17 cells; and induced interleukin-10-producing colonic regulatory cells, and IL-10-independent homeostatic pathways. We propose GUT-108 for treating and preventing relapse for IBD and other inflammatory conditions characterized by unbalanced microbiota and mucosal permeability.
Fecal microbiota transplantation and probiotics have been tested/used as potential therapeutics against inflammatory bowel diseases (IBD). Here the authors use a bottom-up rational consortium design approach that combines well-characterized strains isolated from healthy human stool samples to produce two consortia of metabolically interdependent strains for the treatment of IBD.
Databáze: OpenAIRE
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