Fecal microbiota transplanted from old mice promotes more colonic inflammation, proliferation, and tumor formation in azoxymethane-treated A/J mice than microbiota originating from young mice
ABSTRACTAging is a strong risk factor for colorectal cancer (CRC). It is well established that gut microbial dysbiosis can play a role in the etiology of CRC. Although the composition of the gut microbial community changes with age and is reported to become more pro-inflammatory, it is unclear wheth...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2023.2288187 |
| _version_ | 1827240506876231680 |
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| author | Nicholas A. Crossland Samuel Beck Wei Yu Tan Ming Lo Joel B. Mason Chao Zhang Weimin Guo Jimmy W. Crott |
| author_facet | Nicholas A. Crossland Samuel Beck Wei Yu Tan Ming Lo Joel B. Mason Chao Zhang Weimin Guo Jimmy W. Crott |
| author_sort | Nicholas A. Crossland |
| collection | DOAJ |
| description | ABSTRACTAging is a strong risk factor for colorectal cancer (CRC). It is well established that gut microbial dysbiosis can play a role in the etiology of CRC. Although the composition of the gut microbial community changes with age and is reported to become more pro-inflammatory, it is unclear whether such changes are also pro-tumorigenic for the colon. To address this gap, we conducted fecal microbiota transplants (FMT) from young (DY, ~6 wk) and old (DO, ~72 wk) donor mice into young (8 wk) recipient mice that were pre-treated with antibiotics. After initiating tumorigenesis with azoxymethane, recipients were maintained for 19 wk during which time they received monthly FMT boosters. Compared to recipients of young donors (RY), recipients of old donors (RO) had an approximately 3-fold higher prevalence of histologically confirmed colon tumors (15.8 vs 50%, Chi2 P = .03), approximately 2-fold higher proliferating colonocytes as well as significantly elevated colonic IL-6, IL-1β and Tnf-α. Transcriptomics analysis of the colonic mucosa revealed a striking upregulation of mitochondria-related genes in the RO mice, a finding corroborated by increased mitochondrial abundance. Amongst the differences in fecal microbiome observed between DY and DO mice, the genera Ruminoclostridium, Lachnoclostridium and Marvinbryantia were more abundant in DY mice while the genera Bacteroides and Akkermansia were more abundant in DO mice. Amongst recipients, Ruminoclostridium and Lachnoclostridium were higher in RY mice while Bacteroides was higher in RO mice. Differences in fecal microbiota were observed between young and old mice, some of which persisted upon transplant into recipient mice. Recipients of old donors displayed significantly higher colonic proliferation, inflammation and tumor abundance compared to recipients of young donors. These findings support an etiological role for altered gut microbial communities in the increased risk for CRC with increasing age and establishes that such risk can be transmitted between individuals. |
| first_indexed | 2024-03-08T04:40:33Z |
| format | Article |
| id | doaj.art-1461af85cb5a4f208b551ef8b6668b61 |
| institution | Directory Open Access Journal |
| issn | 1949-0976 1949-0984 |
| language | English |
| last_indexed | 2025-03-21T21:25:41Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj.art-1461af85cb5a4f208b551ef8b6668b612024-05-28T15:04:39ZengTaylor & Francis GroupGut Microbes1949-09761949-09842023-12-0115210.1080/19490976.2023.2288187Fecal microbiota transplanted from old mice promotes more colonic inflammation, proliferation, and tumor formation in azoxymethane-treated A/J mice than microbiota originating from young miceNicholas A. Crossland0Samuel Beck1Wei Yu Tan2Ming Lo3Joel B. Mason4Chao Zhang5Weimin Guo6Jimmy W. Crott7Department of Pathology and Laboratory Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, USADepartment of Dermatology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USAComparative Pathology Laboratory, Boston University National Emerging Infectious Disease Laboratories, Boston, MA, USAComparative Pathology Laboratory, Boston University National Emerging Infectious Disease Laboratories, Boston, MA, USAVitamins and Carcinogenesis Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USADepartment of Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USADepartment of Pathology and Laboratory Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, USADepartment of Pathology and Laboratory Medicine, Boston University Chobanian and Avedisian School of Medicine, Boston, USAABSTRACTAging is a strong risk factor for colorectal cancer (CRC). It is well established that gut microbial dysbiosis can play a role in the etiology of CRC. Although the composition of the gut microbial community changes with age and is reported to become more pro-inflammatory, it is unclear whether such changes are also pro-tumorigenic for the colon. To address this gap, we conducted fecal microbiota transplants (FMT) from young (DY, ~6 wk) and old (DO, ~72 wk) donor mice into young (8 wk) recipient mice that were pre-treated with antibiotics. After initiating tumorigenesis with azoxymethane, recipients were maintained for 19 wk during which time they received monthly FMT boosters. Compared to recipients of young donors (RY), recipients of old donors (RO) had an approximately 3-fold higher prevalence of histologically confirmed colon tumors (15.8 vs 50%, Chi2 P = .03), approximately 2-fold higher proliferating colonocytes as well as significantly elevated colonic IL-6, IL-1β and Tnf-α. Transcriptomics analysis of the colonic mucosa revealed a striking upregulation of mitochondria-related genes in the RO mice, a finding corroborated by increased mitochondrial abundance. Amongst the differences in fecal microbiome observed between DY and DO mice, the genera Ruminoclostridium, Lachnoclostridium and Marvinbryantia were more abundant in DY mice while the genera Bacteroides and Akkermansia were more abundant in DO mice. Amongst recipients, Ruminoclostridium and Lachnoclostridium were higher in RY mice while Bacteroides was higher in RO mice. Differences in fecal microbiota were observed between young and old mice, some of which persisted upon transplant into recipient mice. Recipients of old donors displayed significantly higher colonic proliferation, inflammation and tumor abundance compared to recipients of young donors. These findings support an etiological role for altered gut microbial communities in the increased risk for CRC with increasing age and establishes that such risk can be transmitted between individuals.https://www.tandfonline.com/doi/10.1080/19490976.2023.2288187Microbiomefecal microbiota transplant (FMT)agingcolorectal cancer (CRC)mitochondriainflammation |
| spellingShingle | Nicholas A. Crossland Samuel Beck Wei Yu Tan Ming Lo Joel B. Mason Chao Zhang Weimin Guo Jimmy W. Crott Fecal microbiota transplanted from old mice promotes more colonic inflammation, proliferation, and tumor formation in azoxymethane-treated A/J mice than microbiota originating from young mice Gut Microbes Microbiome fecal microbiota transplant (FMT) aging colorectal cancer (CRC) mitochondria inflammation |
| title | Fecal microbiota transplanted from old mice promotes more colonic inflammation, proliferation, and tumor formation in azoxymethane-treated A/J mice than microbiota originating from young mice |
| title_full | Fecal microbiota transplanted from old mice promotes more colonic inflammation, proliferation, and tumor formation in azoxymethane-treated A/J mice than microbiota originating from young mice |
| title_fullStr | Fecal microbiota transplanted from old mice promotes more colonic inflammation, proliferation, and tumor formation in azoxymethane-treated A/J mice than microbiota originating from young mice |
| title_full_unstemmed | Fecal microbiota transplanted from old mice promotes more colonic inflammation, proliferation, and tumor formation in azoxymethane-treated A/J mice than microbiota originating from young mice |
| title_short | Fecal microbiota transplanted from old mice promotes more colonic inflammation, proliferation, and tumor formation in azoxymethane-treated A/J mice than microbiota originating from young mice |
| title_sort | fecal microbiota transplanted from old mice promotes more colonic inflammation proliferation and tumor formation in azoxymethane treated a j mice than microbiota originating from young mice |
| topic | Microbiome fecal microbiota transplant (FMT) aging colorectal cancer (CRC) mitochondria inflammation |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2023.2288187 |
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