Blocked conversion of Lactobacillus johnsonii derived acetate to butyrate mediates copper-induced epithelial barrier damage in a pig model
Abstract Background High-copper diets have been widely used to promote growth performance of pigs, but excess copper supplementation can also produce negative effects on ecosystem stability and organism health. High-copper supplementation can damage the intestinal barrier and disturb the gut microbi...
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Microbiome |
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| Online Access: | https://doi.org/10.1186/s40168-023-01655-2 |
| _version_ | 1797557843747930112 |
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| author | Yang Wen Luqing Yang Zhenyu Wang Xiaoyi Liu Meng Gao Yunhui Zhang Junjun Wang Pingli He |
| author_facet | Yang Wen Luqing Yang Zhenyu Wang Xiaoyi Liu Meng Gao Yunhui Zhang Junjun Wang Pingli He |
| author_sort | Yang Wen |
| collection | DOAJ |
| description | Abstract Background High-copper diets have been widely used to promote growth performance of pigs, but excess copper supplementation can also produce negative effects on ecosystem stability and organism health. High-copper supplementation can damage the intestinal barrier and disturb the gut microbiome community. However, the specific relationship between high-copper-induced intestinal damage and gut microbiota or its metabolites is unclear. Objective Using fecal microbiota transplantation and metagenomic sequencing, responses of colonic microbiota to a high-copper diet was profiled. In addition, via comparison of specific bacteria and its metabolites rescue, we investigated a network of bacteria-metabolite interactions involving conversion of specific metabolites as a key mechanism linked to copper-induced damage of the colon. Results High copper induced colonic damage, Lactobacillus extinction, and reduction of SCFA (acetate and butyrate) concentrations in pigs. LefSe analysis and q-PCR results confirmed the extinction of L. johnsonii. In addition, transplanting copper-rich fecal microbiota to ABX mice reproduced the gut characteristics of the pig donors. Then, L. johnsonii rescue could restore decreased SCFAs (mainly acetate and butyrate) and colonic barrier damage including thinner mucus layer, reduced colon length, and tight junction protein dysfunction. Given that acetate and butyrate concentrations exhibited a positive correlation with L. johnsonii abundance, we investigated how L. johnsonii exerted its effects by supplementing acetate and butyrate. L. johnsonii and butyrate administration but not acetate could correct the damaged colonic barrier. Acetate administration had no effects on butyrate concentration, indicating blocked conversion from acetate to butyrate. Furthermore, L. johnsonii rescue enriched a series of genera with butyrate-producing ability, mainly Lachnospiraceae NK4A136 group. Conclusions For the first time, we reveal the microbiota-mediated mechanism of high-copper-induced colonic damage in piglets. A high-copper diet can induce extinction of L. johnsonii which leads to colonic barrier damage and loss of SCFA production. Re-establishment of L. johnsonii normalizes the SCFA-producing pathway and restores colonic barrier function. Mechanistically, Lachnospiraceae NK4A136 group mediated conversion of acetate produced by L. johnsonii to butyrate is indispensable in the protection of colonic barrier function. Collectively, these findings provide a feasible mitigation strategy for gut damage caused by high-copper diets. Video Abstract |
| first_indexed | 2024-03-10T17:22:00Z |
| format | Article |
| id | doaj.art-f9e19206fba947d3b606a44d1a1f7226 |
| institution | Directory Open Access Journal |
| issn | 2049-2618 |
| language | English |
| last_indexed | 2024-03-10T17:22:00Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
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| series | Microbiome |
| spelling | doaj.art-f9e19206fba947d3b606a44d1a1f72262023-11-20T10:19:35ZengBMCMicrobiome2049-26182023-09-0111111910.1186/s40168-023-01655-2Blocked conversion of Lactobacillus johnsonii derived acetate to butyrate mediates copper-induced epithelial barrier damage in a pig modelYang Wen0Luqing Yang1Zhenyu Wang2Xiaoyi Liu3Meng Gao4Yunhui Zhang5Junjun Wang6Pingli He7State Key Laboratory of Animal Nutrition, Frontiers Science Center for Molecular Design Breeding (MOE), China Agricultural UniversityState Key Laboratory of Animal Nutrition, Frontiers Science Center for Molecular Design Breeding (MOE), China Agricultural UniversityState Key Laboratory of Animal Nutrition, Frontiers Science Center for Molecular Design Breeding (MOE), China Agricultural UniversityState Key Laboratory of Animal Nutrition, Frontiers Science Center for Molecular Design Breeding (MOE), China Agricultural UniversityState Key Laboratory of Farm Animal Biotech Breeding, College of Biological Sciences, China Agricultural UniversityCollege of Environmental Science and Engineering, Tongji UniversityState Key Laboratory of Animal Nutrition, Frontiers Science Center for Molecular Design Breeding (MOE), China Agricultural UniversityState Key Laboratory of Animal Nutrition, Frontiers Science Center for Molecular Design Breeding (MOE), China Agricultural UniversityAbstract Background High-copper diets have been widely used to promote growth performance of pigs, but excess copper supplementation can also produce negative effects on ecosystem stability and organism health. High-copper supplementation can damage the intestinal barrier and disturb the gut microbiome community. However, the specific relationship between high-copper-induced intestinal damage and gut microbiota or its metabolites is unclear. Objective Using fecal microbiota transplantation and metagenomic sequencing, responses of colonic microbiota to a high-copper diet was profiled. In addition, via comparison of specific bacteria and its metabolites rescue, we investigated a network of bacteria-metabolite interactions involving conversion of specific metabolites as a key mechanism linked to copper-induced damage of the colon. Results High copper induced colonic damage, Lactobacillus extinction, and reduction of SCFA (acetate and butyrate) concentrations in pigs. LefSe analysis and q-PCR results confirmed the extinction of L. johnsonii. In addition, transplanting copper-rich fecal microbiota to ABX mice reproduced the gut characteristics of the pig donors. Then, L. johnsonii rescue could restore decreased SCFAs (mainly acetate and butyrate) and colonic barrier damage including thinner mucus layer, reduced colon length, and tight junction protein dysfunction. Given that acetate and butyrate concentrations exhibited a positive correlation with L. johnsonii abundance, we investigated how L. johnsonii exerted its effects by supplementing acetate and butyrate. L. johnsonii and butyrate administration but not acetate could correct the damaged colonic barrier. Acetate administration had no effects on butyrate concentration, indicating blocked conversion from acetate to butyrate. Furthermore, L. johnsonii rescue enriched a series of genera with butyrate-producing ability, mainly Lachnospiraceae NK4A136 group. Conclusions For the first time, we reveal the microbiota-mediated mechanism of high-copper-induced colonic damage in piglets. A high-copper diet can induce extinction of L. johnsonii which leads to colonic barrier damage and loss of SCFA production. Re-establishment of L. johnsonii normalizes the SCFA-producing pathway and restores colonic barrier function. Mechanistically, Lachnospiraceae NK4A136 group mediated conversion of acetate produced by L. johnsonii to butyrate is indispensable in the protection of colonic barrier function. Collectively, these findings provide a feasible mitigation strategy for gut damage caused by high-copper diets. Video Abstracthttps://doi.org/10.1186/s40168-023-01655-2Lactobacillus johnsoniiColonic barrierShort-chain fatty acidMicrobiotaCopper |
| spellingShingle | Yang Wen Luqing Yang Zhenyu Wang Xiaoyi Liu Meng Gao Yunhui Zhang Junjun Wang Pingli He Blocked conversion of Lactobacillus johnsonii derived acetate to butyrate mediates copper-induced epithelial barrier damage in a pig model Microbiome Lactobacillus johnsonii Colonic barrier Short-chain fatty acid Microbiota Copper |
| title | Blocked conversion of Lactobacillus johnsonii derived acetate to butyrate mediates copper-induced epithelial barrier damage in a pig model |
| title_full | Blocked conversion of Lactobacillus johnsonii derived acetate to butyrate mediates copper-induced epithelial barrier damage in a pig model |
| title_fullStr | Blocked conversion of Lactobacillus johnsonii derived acetate to butyrate mediates copper-induced epithelial barrier damage in a pig model |
| title_full_unstemmed | Blocked conversion of Lactobacillus johnsonii derived acetate to butyrate mediates copper-induced epithelial barrier damage in a pig model |
| title_short | Blocked conversion of Lactobacillus johnsonii derived acetate to butyrate mediates copper-induced epithelial barrier damage in a pig model |
| title_sort | blocked conversion of lactobacillus johnsonii derived acetate to butyrate mediates copper induced epithelial barrier damage in a pig model |
| topic | Lactobacillus johnsonii Colonic barrier Short-chain fatty acid Microbiota Copper |
| url | https://doi.org/10.1186/s40168-023-01655-2 |
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