Transplant of microbiota from Crohn’s disease patients to germ-free mice results in colitis
ABSTRACTAlthough the role of the intestinal microbiota in the pathogenesis of inflammatory bowel disease (IBD) is beyond debate, attempts to verify the causative role of IBD-associated dysbiosis have been limited to reports of promoting the disease in genetically susceptible mice or in chemically in...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Gut Microbes |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2024.2333483 |
| _version_ | 1797242729666707456 |
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| author | Irshad Ali Sheikh Jared Bianchi-Smak Daniel Laubitz Gabriele Schiro Monica T. Midura-Kiela David G. Besselsen Gayatri Vedantam Sara Jarmakiewicz Rafał Filip Fayez K. Ghishan Nan Gao Pawel R. Kiela |
| author_facet | Irshad Ali Sheikh Jared Bianchi-Smak Daniel Laubitz Gabriele Schiro Monica T. Midura-Kiela David G. Besselsen Gayatri Vedantam Sara Jarmakiewicz Rafał Filip Fayez K. Ghishan Nan Gao Pawel R. Kiela |
| author_sort | Irshad Ali Sheikh |
| collection | DOAJ |
| description | ABSTRACTAlthough the role of the intestinal microbiota in the pathogenesis of inflammatory bowel disease (IBD) is beyond debate, attempts to verify the causative role of IBD-associated dysbiosis have been limited to reports of promoting the disease in genetically susceptible mice or in chemically induced colitis. We aimed to further test the host response to fecal microbiome transplantation (FMT) from Crohn’s disease patients on mucosal homeostasis in ex-germ-free (xGF) mice. We characterized and transferred fecal microbiota from healthy patients and patients with defined Crohn’s ileocolitis (CD_L3) to germ-free mice and analyzed the resulting microbial and mucosal homeostasis by 16S profiling, shotgun metagenomics, histology, immunofluorescence (IF) and RNAseq analysis. We observed a markedly reduced engraftment of CD_L3 microbiome compared to healthy control microbiota. FMT from CD_L3 patients did not lead to ileitis but resulted in colitis with features consistent with CD: a discontinued pattern of colitis, more proximal colonic localization, enlarged isolated lymphoid follicles and/or tertiary lymphoid organ neogenesis, and a transcriptomic pattern consistent with epithelial reprograming and promotion of the Paneth cell-like signature in the proximal colon and immune dysregulation characteristic of CD. The observed inflammatory response was associated with persistently increased abundance of Ruminococcus gnavus, Erysipelatoclostridium ramosum, Faecalimonas umbilicate, Blautia hominis, Clostridium butyricum, and C. paraputrificum and unexpected growth of toxigenic C. difficile, which was below the detection level in the community used for inoculation. Our study provides the first evidence that the transfer of a dysbiotic community from CD patients can lead to spontaneous inflammatory changes in the colon of xGF mice and identifies a signature microbial community capable of promoting colonization of pathogenic and conditionally pathogenic bacteria. |
| first_indexed | 2024-04-24T18:43:51Z |
| format | Article |
| id | doaj.art-1f11d92deb564e249b4081fe68ea04d4 |
| institution | Directory Open Access Journal |
| issn | 1949-0976 1949-0984 |
| language | English |
| last_indexed | 2024-04-24T18:43:51Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj.art-1f11d92deb564e249b4081fe68ea04d42024-03-27T07:24:04ZengTaylor & Francis GroupGut Microbes1949-09761949-09842024-12-0116110.1080/19490976.2024.2333483Transplant of microbiota from Crohn’s disease patients to germ-free mice results in colitisIrshad Ali Sheikh0Jared Bianchi-Smak1Daniel Laubitz2Gabriele Schiro3Monica T. Midura-Kiela4David G. Besselsen5Gayatri Vedantam6Sara Jarmakiewicz7Rafał Filip8Fayez K. Ghishan9Nan Gao10Pawel R. Kiela11Daniel Cracchiolo Institute for Pediatric Autoimmune Disease Research, Steele Children’s Research Center, Department of Pediatrics, University of Arizona, Tucson, AZ, USADepartment of Biological Sciences, Rutgers University, Newark, NJ, USADaniel Cracchiolo Institute for Pediatric Autoimmune Disease Research, Steele Children’s Research Center, Department of Pediatrics, University of Arizona, Tucson, AZ, USADaniel Cracchiolo Institute for Pediatric Autoimmune Disease Research, Steele Children’s Research Center, Department of Pediatrics, University of Arizona, Tucson, AZ, USADaniel Cracchiolo Institute for Pediatric Autoimmune Disease Research, Steele Children’s Research Center, Department of Pediatrics, University of Arizona, Tucson, AZ, USAPediatrics, University Animal Care, University of Arizona, Tucson, AZ, USASchool of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, AZ, USAInstitute of Health Sciences, Medical College of Rzeszow, Rzeszow University, Rzeszow, PolandInstitute of Medicine, Medical College of Rzeszow University, Rzeszow, PolandDaniel Cracchiolo Institute for Pediatric Autoimmune Disease Research, Steele Children’s Research Center, Department of Pediatrics, University of Arizona, Tucson, AZ, USADepartment of Biological Sciences, Rutgers University, Newark, NJ, USADaniel Cracchiolo Institute for Pediatric Autoimmune Disease Research, Steele Children’s Research Center, Department of Pediatrics, University of Arizona, Tucson, AZ, USAABSTRACTAlthough the role of the intestinal microbiota in the pathogenesis of inflammatory bowel disease (IBD) is beyond debate, attempts to verify the causative role of IBD-associated dysbiosis have been limited to reports of promoting the disease in genetically susceptible mice or in chemically induced colitis. We aimed to further test the host response to fecal microbiome transplantation (FMT) from Crohn’s disease patients on mucosal homeostasis in ex-germ-free (xGF) mice. We characterized and transferred fecal microbiota from healthy patients and patients with defined Crohn’s ileocolitis (CD_L3) to germ-free mice and analyzed the resulting microbial and mucosal homeostasis by 16S profiling, shotgun metagenomics, histology, immunofluorescence (IF) and RNAseq analysis. We observed a markedly reduced engraftment of CD_L3 microbiome compared to healthy control microbiota. FMT from CD_L3 patients did not lead to ileitis but resulted in colitis with features consistent with CD: a discontinued pattern of colitis, more proximal colonic localization, enlarged isolated lymphoid follicles and/or tertiary lymphoid organ neogenesis, and a transcriptomic pattern consistent with epithelial reprograming and promotion of the Paneth cell-like signature in the proximal colon and immune dysregulation characteristic of CD. The observed inflammatory response was associated with persistently increased abundance of Ruminococcus gnavus, Erysipelatoclostridium ramosum, Faecalimonas umbilicate, Blautia hominis, Clostridium butyricum, and C. paraputrificum and unexpected growth of toxigenic C. difficile, which was below the detection level in the community used for inoculation. Our study provides the first evidence that the transfer of a dysbiotic community from CD patients can lead to spontaneous inflammatory changes in the colon of xGF mice and identifies a signature microbial community capable of promoting colonization of pathogenic and conditionally pathogenic bacteria.https://www.tandfonline.com/doi/10.1080/19490976.2024.2333483Crohn’s ileocolitismicrobiotafecal microbiome transplantgerm-free miceinflammation |
| spellingShingle | Irshad Ali Sheikh Jared Bianchi-Smak Daniel Laubitz Gabriele Schiro Monica T. Midura-Kiela David G. Besselsen Gayatri Vedantam Sara Jarmakiewicz Rafał Filip Fayez K. Ghishan Nan Gao Pawel R. Kiela Transplant of microbiota from Crohn’s disease patients to germ-free mice results in colitis Gut Microbes Crohn’s ileocolitis microbiota fecal microbiome transplant germ-free mice inflammation |
| title | Transplant of microbiota from Crohn’s disease patients to germ-free mice results in colitis |
| title_full | Transplant of microbiota from Crohn’s disease patients to germ-free mice results in colitis |
| title_fullStr | Transplant of microbiota from Crohn’s disease patients to germ-free mice results in colitis |
| title_full_unstemmed | Transplant of microbiota from Crohn’s disease patients to germ-free mice results in colitis |
| title_short | Transplant of microbiota from Crohn’s disease patients to germ-free mice results in colitis |
| title_sort | transplant of microbiota from crohn s disease patients to germ free mice results in colitis |
| topic | Crohn’s ileocolitis microbiota fecal microbiome transplant germ-free mice inflammation |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2024.2333483 |
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