Creation of a non-Western humanized gnotobiotic mouse model through the transplantation of rural African fecal microbiota
ABSTRACT Gut microbiota are increasingly being recognized as a contributing factor in the etiology of numerous diseases and as a potential determinant in the immune response to various treatments. Recent work has suggested that the suboptimal immunogenic response to vaccination in low- and middle-in...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2023-12-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.01554-23 |
| _version_ | 1797393599598428160 |
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| author | Kristin M. Van Den Ham Morgan R. Little Olivia J. Bednarski Elizabeth M. Fusco Rabindra K. Mandal Riten Mitra Shanping Li Safiatou Doumbo Didier Doumtabe Kassoum Kayentao Aissata Ongoiba Boubacar Traore Peter D. Crompton Nathan W. Schmidt |
| author_facet | Kristin M. Van Den Ham Morgan R. Little Olivia J. Bednarski Elizabeth M. Fusco Rabindra K. Mandal Riten Mitra Shanping Li Safiatou Doumbo Didier Doumtabe Kassoum Kayentao Aissata Ongoiba Boubacar Traore Peter D. Crompton Nathan W. Schmidt |
| author_sort | Kristin M. Van Den Ham |
| collection | DOAJ |
| description | ABSTRACT Gut microbiota are increasingly being recognized as a contributing factor in the etiology of numerous diseases and as a potential determinant in the immune response to various treatments. Recent work has suggested that the suboptimal immunogenic response to vaccination in low- and middle-income countries may be associated with differences in the gut microbiome, which are known to be substantially different between Western and non-Western countries. However, insufficient consideration has been given to the characterization of non-Western microbiomes and their relationship with well-being and immunity. Humanized gnotobiotic mouse models have been used to better understand the causal associations between the gut microbiota and health outcomes but have largely been limited to the study of Western microbiota. Thus, we were interested in determining the applicability of gavage strategies used to humanize germ-free mice with Western microbiota to the humanization of germ-free mice with rural African fecal samples. Here, we assessed the impact of the number and frequency of gavages and the effect of a donor-matched diet on the colonization of Malian fecal microbiota in germ-free mice. One gavage was insufficient to provide a stable establishment of the Malian microbiome, whereas four weekly gavages resulted in a more consistent colonization of the human donor taxa. Interestingly, the donor-matched diet did not improve colonization over the fixed-formula, grain-based mouse chow. Subsequent phenotypic studies using African gut microbiota-humanized gnotobiotic mouse models will allow for a better understanding of the interaction between African gut microbiota and well-being and potentially aid in developing improved treatments for microbiota-dependent diseases in non-Western populations. IMPORTANCE There is increasing evidence that microbes residing within the intestines (gut microbiota) play important roles in the well-being of humans. Yet, there are considerable challenges in determining the specific role of gut microbiota in human diseases owing to the complexity of diverse internal and environmental factors that can contribute to diseases. Mice devoid of all microorganisms (germ-free mice) can be colonized with human stool samples to examine the specific contribution of the gut microbiota to a disease. These approaches have been primarily focused on stool samples obtained from individuals in Western countries. Thus, there is limited understanding as to whether the same methods used to colonize germ-free mice with stool from Western individuals would apply to the colonization of germ-free mice with stool from non-Western individuals. Here, we report the results from colonizing germ-free mice with stool samples of Malian children. |
| first_indexed | 2024-03-09T00:06:10Z |
| format | Article |
| id | doaj.art-56f56666f1764321987a3ac098d01687 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-03-09T00:06:10Z |
| publishDate | 2023-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-56f56666f1764321987a3ac098d016872023-12-12T13:17:19ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972023-12-0111610.1128/spectrum.01554-23Creation of a non-Western humanized gnotobiotic mouse model through the transplantation of rural African fecal microbiotaKristin M. Van Den Ham0Morgan R. Little1Olivia J. Bednarski2Elizabeth M. Fusco3Rabindra K. Mandal4Riten Mitra5Shanping Li6Safiatou Doumbo7Didier Doumtabe8Kassoum Kayentao9Aissata Ongoiba10Boubacar Traore11Peter D. Crompton12Nathan W. Schmidt13Department of Pediatrics, Ryan White Center for Pediatric Infectious Diseases and Global Health, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine , Indianapolis, Indiana, USADepartment of Pediatrics, Ryan White Center for Pediatric Infectious Diseases and Global Health, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine , Indianapolis, Indiana, USADepartment of Pediatrics, Ryan White Center for Pediatric Infectious Diseases and Global Health, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine , Indianapolis, Indiana, USADepartment of Pediatrics, Ryan White Center for Pediatric Infectious Diseases and Global Health, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine , Indianapolis, Indiana, USADepartment of Pediatrics, Ryan White Center for Pediatric Infectious Diseases and Global Health, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine , Indianapolis, Indiana, USADepartment of Bioinformatics and Biostatistics, University of Louisville , Louisville, Kentucky, USAMalaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Rockville, Maryland, USAMali International Center of Excellence in Research, Malaria Research and Training Center, University of Sciences, Techniques and Technologies of Bamako , Bamako, MaliMali International Center of Excellence in Research, Malaria Research and Training Center, University of Sciences, Techniques and Technologies of Bamako , Bamako, MaliMali International Center of Excellence in Research, Malaria Research and Training Center, University of Sciences, Techniques and Technologies of Bamako , Bamako, MaliMali International Center of Excellence in Research, Malaria Research and Training Center, University of Sciences, Techniques and Technologies of Bamako , Bamako, MaliMali International Center of Excellence in Research, Malaria Research and Training Center, University of Sciences, Techniques and Technologies of Bamako , Bamako, MaliMalaria Infection Biology and Immunity Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Rockville, Maryland, USADepartment of Pediatrics, Ryan White Center for Pediatric Infectious Diseases and Global Health, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine , Indianapolis, Indiana, USAABSTRACT Gut microbiota are increasingly being recognized as a contributing factor in the etiology of numerous diseases and as a potential determinant in the immune response to various treatments. Recent work has suggested that the suboptimal immunogenic response to vaccination in low- and middle-income countries may be associated with differences in the gut microbiome, which are known to be substantially different between Western and non-Western countries. However, insufficient consideration has been given to the characterization of non-Western microbiomes and their relationship with well-being and immunity. Humanized gnotobiotic mouse models have been used to better understand the causal associations between the gut microbiota and health outcomes but have largely been limited to the study of Western microbiota. Thus, we were interested in determining the applicability of gavage strategies used to humanize germ-free mice with Western microbiota to the humanization of germ-free mice with rural African fecal samples. Here, we assessed the impact of the number and frequency of gavages and the effect of a donor-matched diet on the colonization of Malian fecal microbiota in germ-free mice. One gavage was insufficient to provide a stable establishment of the Malian microbiome, whereas four weekly gavages resulted in a more consistent colonization of the human donor taxa. Interestingly, the donor-matched diet did not improve colonization over the fixed-formula, grain-based mouse chow. Subsequent phenotypic studies using African gut microbiota-humanized gnotobiotic mouse models will allow for a better understanding of the interaction between African gut microbiota and well-being and potentially aid in developing improved treatments for microbiota-dependent diseases in non-Western populations. IMPORTANCE There is increasing evidence that microbes residing within the intestines (gut microbiota) play important roles in the well-being of humans. Yet, there are considerable challenges in determining the specific role of gut microbiota in human diseases owing to the complexity of diverse internal and environmental factors that can contribute to diseases. Mice devoid of all microorganisms (germ-free mice) can be colonized with human stool samples to examine the specific contribution of the gut microbiota to a disease. These approaches have been primarily focused on stool samples obtained from individuals in Western countries. Thus, there is limited understanding as to whether the same methods used to colonize germ-free mice with stool from Western individuals would apply to the colonization of germ-free mice with stool from non-Western individuals. Here, we report the results from colonizing germ-free mice with stool samples of Malian children.https://journals.asm.org/doi/10.1128/spectrum.01554-23germ free miceintestinal colonizationnon-Western stool |
| spellingShingle | Kristin M. Van Den Ham Morgan R. Little Olivia J. Bednarski Elizabeth M. Fusco Rabindra K. Mandal Riten Mitra Shanping Li Safiatou Doumbo Didier Doumtabe Kassoum Kayentao Aissata Ongoiba Boubacar Traore Peter D. Crompton Nathan W. Schmidt Creation of a non-Western humanized gnotobiotic mouse model through the transplantation of rural African fecal microbiota Microbiology Spectrum germ free mice intestinal colonization non-Western stool |
| title | Creation of a non-Western humanized gnotobiotic mouse model through the transplantation of rural African fecal microbiota |
| title_full | Creation of a non-Western humanized gnotobiotic mouse model through the transplantation of rural African fecal microbiota |
| title_fullStr | Creation of a non-Western humanized gnotobiotic mouse model through the transplantation of rural African fecal microbiota |
| title_full_unstemmed | Creation of a non-Western humanized gnotobiotic mouse model through the transplantation of rural African fecal microbiota |
| title_short | Creation of a non-Western humanized gnotobiotic mouse model through the transplantation of rural African fecal microbiota |
| title_sort | creation of a non western humanized gnotobiotic mouse model through the transplantation of rural african fecal microbiota |
| topic | germ free mice intestinal colonization non-Western stool |
| url | https://journals.asm.org/doi/10.1128/spectrum.01554-23 |
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