Antibiotic-associated dysbiosis affects the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in experimental colitis models

• Published in: Microbiome Vol. 9; no. 1; pp. 39 - 15
• Main Authors: Strati, Francesco, Pujolassos, Meritxell, Burrello, Claudia, Giuffrè, Maria Rita, Lattanzi, Georgia, Caprioli, Flavio, Troisi, Jacopo, Facciotti, Federica
• Format: Journal Article
• Language: English
• Published: England BioMed Central 06.02.2021; BMC
• Subjects: Animals; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - pharmacology; Antibiotics; CD4 antigen; Colitis; Colitis - chemically induced; Colitis - immunology; Colitis - microbiology; Colitis - pathology; Colon; Community structure; Digestive system; Disease; Disease Models, Animal; Dysbacteriosis; Dysbiosis - chemically induced; Dysbiosis - microbiology; Fecal Microbiota Transplantation; Fecal microflora; Feces; Female; FMT; Gastrointestinal Microbiome - drug effects; Gastrointestinal Microbiome - immunology; Gastrointestinal tract; Gene amplification; Gene expression; Gut microbiota; Helper cells; Homeostasis; Humans; IBD; Immune response; Immune system; Inflammation; Inflammatory bowel disease; iNKT; Innate immunity; Interleukin 1; Interleukin 10; Intestinal microflora; Intestine; Lamina propria; Leukocytes (mononuclear); Library collections; Lymphocytes T; Male; Metabolites; Metronidazole; Metronidazole - pharmacology; Mice; Microbiomes; Microbiota; Natural Killer T-Cells - drug effects; Natural Killer T-Cells - immunology; Oxidative metabolism; Oxidative stress; Streptomycin; Streptomycin - adverse effects; Th1 Cells - drug effects; Th1 Cells - immunology; Th17 Cells - drug effects; Th17 Cells - immunology; Transplantation; Vancomycin; Vancomycin - adverse effects; United States > US; Italy; Gut microbiota; IBD; Antibiotics; FMT; iNKT
• DOI: 10.1186/s40168-020-00991-x
• ISSN: 2049-2618

The gut microbiota plays a central role in host physiology and in several pathological mechanisms in humans. Antibiotics compromise the composition and functions of the gut microbiota inducing long-lasting detrimental effects on the host. Recent studies suggest that the efficacy of different clinical therapies depends on the action of the gut microbiota. Here, we investigated how different antibiotic treatments affect the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in an experimental colitis model and in ex vivo experiments with human intestinal biopsies. Murine fecal donors were pre-treated with different antibiotics, i.e., vancomycin, streptomycin, and metronidazole before FMT administration to colitic animals. The analysis of the gut microbiome, fecal metabolome, and the immunophenotyping of colonic lamina propria immune cells revealed that antibiotic pre-treatment significantly influences the capability of the microbiota to control intestinal inflammation. Streptomycin and vancomycin-treated microbiota failed to control intestinal inflammation and were characterized by the blooming of pathobionts previously associated with IBD as well as with metabolites related to the presence of oxidative stress and metabolism of simple sugars. On the contrary, the metronidazole-treated microbiota retained its ability to control inflammation co-occurring with the enrichment of Lactobacillus and of innate immune responses involving iNKT cells. Furthermore, ex vivo cultures of human intestinal lamina propria mononuclear cells and iNKT cell clones from IBD patients with vancomycin pre-treated sterile fecal water showed a Th1/Th17 skewing in CD4 T-cell populations; metronidazole, on the other hand, induced the polarization of iNKT cells toward the production of IL10. Diverse antibiotic regimens affect the ability of the gut microbiota to control intestinal inflammation in experimental colitis by altering the microbial community structure and microbiota-derived metabolites. Video Abstract.