Akkermansia and its metabolites play key roles in the treatment of campylobacteriosis in mice
IntroductionCampylobacter jejuni (C. jejuni) is a common food-borne bacterial pathogen that can use the host’s innate immune response to induce the development of colitis. There has been some research on the role of normal intestinal flora in C. jejuni-induced colitis, but the mechanisms that play a...
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| Format: | Article |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1061627/full |
| _version_ | 1797955374571061248 |
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| author | Lai Jiang Chunchun Yuan Wenxin Ye Qixin Huang Zhuo Chen Wenzi Wu Lichun Qian |
| author_facet | Lai Jiang Chunchun Yuan Wenxin Ye Qixin Huang Zhuo Chen Wenzi Wu Lichun Qian |
| author_sort | Lai Jiang |
| collection | DOAJ |
| description | IntroductionCampylobacter jejuni (C. jejuni) is a common food-borne bacterial pathogen that can use the host’s innate immune response to induce the development of colitis. There has been some research on the role of normal intestinal flora in C. jejuni-induced colitis, but the mechanisms that play a central role in resistance to C. jejuni infection have not been explored.MethodsWe treated Campylobacter jejuni-infected mice with fecal microbiota transplantation (FMT), oral butyric acid and deoxycholic acid in a controlled trial and analyzed the possible mechanisms of treatment by a combination of chromatography, immunohistochemistry, fluorescence in situ hybridization, 16s rRNA gene, proteomics and western blot techniques.ResultsWe first investigated the therapeutic effect of FMT on C. jejuni infection. The results showed that FMT significantly reduced the inflammatory response and blocked the invasion of C.jejuni into the colonic tissue. We observed a significant increase in the abundance of Akkermansia in the colon of mice after FMT, as well as a significant increase in the levels of butyric acid and deoxycholic acid. We next demonstrated that oral administration of sodium butyrate or deoxycholic acid had a similar therapeutic effect. Further proteomic analysis showed that C.jejuni induced colitis mainly through activation of the PI3K-AKT signaling pathway and MAPK signaling pathway, whereas Akkermansia, the core flora of FMT, and the gut microbial metabolites butyric acid and deoxycholic acid both inhibited these signaling pathways to counteract the infection of C. jejuni and alleviate colitis. Finally, we verified the above idea by in vitro cellular assays. In conclusion, FMT is highly effective in the treatment of colitis caused by C. jejuni, with which Akkermansia and butyric and deoxycholic acids are closely associated.The present study demonstrates that Akkermansia and butyric and deoxycholic acids are effective in the treatment of colitis caused by C. jejuni.DiscussionThis is the first time that Akkermansia has been found to be effective in fighting pathogens, which provides new ideas and insights into the use of FMT to alleviate colitis caused by C. jejuni and Akkermansia as a treatment for intestinal sexually transmitted diseases caused by various pathogens. |
| first_indexed | 2024-04-10T23:32:06Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T23:32:06Z |
| publishDate | 2023-01-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-b2836ead1996481783b3ea482e93f98e2023-01-12T05:33:23ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011310.3389/fimmu.2022.10616271061627Akkermansia and its metabolites play key roles in the treatment of campylobacteriosis in miceLai Jiang0Chunchun Yuan1Wenxin Ye2Qixin Huang3Zhuo Chen4Wenzi Wu5Lichun Qian6Key Laboratory of Animal Nutrition and Feed Science, Ministry of Agriculture and Rural Affairs, College of Animal Sciences, Zhejiang University, Hangzhou, ChinaKey Laboratory of Animal Nutrition and Feed Science, Ministry of Agriculture and Rural Affairs, College of Animal Sciences, Zhejiang University, Hangzhou, ChinaHainan Institute of Zhejiang University, Sanya, ChinaKey Laboratory of Animal Nutrition and Feed Science, Ministry of Agriculture and Rural Affairs, College of Animal Sciences, Zhejiang University, Hangzhou, ChinaHainan Institute of Zhejiang University, Sanya, ChinaHainan Institute of Zhejiang University, Sanya, ChinaKey Laboratory of Animal Nutrition and Feed Science, Ministry of Agriculture and Rural Affairs, College of Animal Sciences, Zhejiang University, Hangzhou, ChinaIntroductionCampylobacter jejuni (C. jejuni) is a common food-borne bacterial pathogen that can use the host’s innate immune response to induce the development of colitis. There has been some research on the role of normal intestinal flora in C. jejuni-induced colitis, but the mechanisms that play a central role in resistance to C. jejuni infection have not been explored.MethodsWe treated Campylobacter jejuni-infected mice with fecal microbiota transplantation (FMT), oral butyric acid and deoxycholic acid in a controlled trial and analyzed the possible mechanisms of treatment by a combination of chromatography, immunohistochemistry, fluorescence in situ hybridization, 16s rRNA gene, proteomics and western blot techniques.ResultsWe first investigated the therapeutic effect of FMT on C. jejuni infection. The results showed that FMT significantly reduced the inflammatory response and blocked the invasion of C.jejuni into the colonic tissue. We observed a significant increase in the abundance of Akkermansia in the colon of mice after FMT, as well as a significant increase in the levels of butyric acid and deoxycholic acid. We next demonstrated that oral administration of sodium butyrate or deoxycholic acid had a similar therapeutic effect. Further proteomic analysis showed that C.jejuni induced colitis mainly through activation of the PI3K-AKT signaling pathway and MAPK signaling pathway, whereas Akkermansia, the core flora of FMT, and the gut microbial metabolites butyric acid and deoxycholic acid both inhibited these signaling pathways to counteract the infection of C. jejuni and alleviate colitis. Finally, we verified the above idea by in vitro cellular assays. In conclusion, FMT is highly effective in the treatment of colitis caused by C. jejuni, with which Akkermansia and butyric and deoxycholic acids are closely associated.The present study demonstrates that Akkermansia and butyric and deoxycholic acids are effective in the treatment of colitis caused by C. jejuni.DiscussionThis is the first time that Akkermansia has been found to be effective in fighting pathogens, which provides new ideas and insights into the use of FMT to alleviate colitis caused by C. jejuni and Akkermansia as a treatment for intestinal sexually transmitted diseases caused by various pathogens.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1061627/fullCampylobacter jejunifecal microbiota transplantationAkkermansiabutyric aciddeoxycholic acidPI3K-AKT pathway |
| spellingShingle | Lai Jiang Chunchun Yuan Wenxin Ye Qixin Huang Zhuo Chen Wenzi Wu Lichun Qian Akkermansia and its metabolites play key roles in the treatment of campylobacteriosis in mice Frontiers in Immunology Campylobacter jejuni fecal microbiota transplantation Akkermansia butyric acid deoxycholic acid PI3K-AKT pathway |
| title | Akkermansia and its metabolites play key roles in the treatment of campylobacteriosis in mice |
| title_full | Akkermansia and its metabolites play key roles in the treatment of campylobacteriosis in mice |
| title_fullStr | Akkermansia and its metabolites play key roles in the treatment of campylobacteriosis in mice |
| title_full_unstemmed | Akkermansia and its metabolites play key roles in the treatment of campylobacteriosis in mice |
| title_short | Akkermansia and its metabolites play key roles in the treatment of campylobacteriosis in mice |
| title_sort | akkermansia and its metabolites play key roles in the treatment of campylobacteriosis in mice |
| topic | Campylobacter jejuni fecal microbiota transplantation Akkermansia butyric acid deoxycholic acid PI3K-AKT pathway |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1061627/full |
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