Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney Disease
Disturbance of circulating metabolites and disorders of the gut microbiota are involved in the progression of diabetic kidney disease (DKD). However, there is limited research on the relationship between serum metabolites and gut microbiota, and their involvement in DKD. In this study, using an expe...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-04-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.872988/full |
| _version_ | 1817992414702338048 |
|---|---|
| author | Bo Zhang Bo Zhang Yuzhou Wan Xuefeng Zhou Haojun Zhang Hailing Zhao Liang Ma Xi Dong Meihua Yan Tingting Zhao Tingting Zhao Ping Li |
| author_facet | Bo Zhang Bo Zhang Yuzhou Wan Xuefeng Zhou Haojun Zhang Hailing Zhao Liang Ma Xi Dong Meihua Yan Tingting Zhao Tingting Zhao Ping Li |
| author_sort | Bo Zhang |
| collection | DOAJ |
| description | Disturbance of circulating metabolites and disorders of the gut microbiota are involved in the progression of diabetic kidney disease (DKD). However, there is limited research on the relationship between serum metabolites and gut microbiota, and their involvement in DKD. In this study, using an experimental DKD rat model induced by combining streptozotocin injection and unilateral nephrectomy, we employed untargeted metabolomics and 16S rRNA gene sequencing to explore the relationship between the metabolic profile and the structure and function of gut microbiota. Striking alterations took place in 140 serum metabolites, as well as in the composition and function of rat gut microbiota. These changes were mainly associated with carbohydrate, lipid, and amino acid metabolism. In these pathways, isomaltose, D-mannose, galactonic acid, citramalic acid, and prostaglandin B2 were significantly upregulated. 3-(2-Hydroxyethyl)indole, 3-methylindole, and indoleacrylic acid were downregulated and were the critical metabolites in the DKD model. Furthermore, the levels of these three indoles were restored after treatment with the traditional Chinese herbal medicine Tangshen Formula. At the genera level, g_Eubacterium_nodatum_group, g_Lactobacillus, and g_Faecalibaculum were most involved in metabolic disorders in the progression of DKD. Notably, the circulating lipid metabolites had a strong relationship with DKD-related parameters and were especially negatively related to the mesangial matrix area. Serum lipid indices (TG and TC) and UACR were directly associated with certain microbial genera. In conclusion, the present research verified the anomalous circulating metabolites and gut microbiota in DKD progression. We also identified the potential metabolic and microbial targets for the treatment of DKD. |
| first_indexed | 2024-04-14T01:25:59Z |
| format | Article |
| id | doaj.art-160efa75f14b43b385527191ac8c8eae |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-14T01:25:59Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-160efa75f14b43b385527191ac8c8eae2022-12-22T02:20:25ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-04-011310.3389/fphar.2022.872988872988Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney DiseaseBo Zhang0Bo Zhang1Yuzhou Wan2Xuefeng Zhou3Haojun Zhang4Hailing Zhao5Liang Ma6Xi Dong7Meihua Yan8Tingting Zhao9Tingting Zhao10Ping Li11Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China–Japan Friendship Hospital, Beijing, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China–Japan Friendship Hospital, Beijing, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China–Japan Friendship Hospital, Beijing, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China–Japan Friendship Hospital, Beijing, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China–Japan Friendship Hospital, Beijing, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China–Japan Friendship Hospital, Beijing, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China–Japan Friendship Hospital, Beijing, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China–Japan Friendship Hospital, Beijing, ChinaGraduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China–Japan Friendship Hospital, Beijing, ChinaBeijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China–Japan Friendship Hospital, Beijing, ChinaDisturbance of circulating metabolites and disorders of the gut microbiota are involved in the progression of diabetic kidney disease (DKD). However, there is limited research on the relationship between serum metabolites and gut microbiota, and their involvement in DKD. In this study, using an experimental DKD rat model induced by combining streptozotocin injection and unilateral nephrectomy, we employed untargeted metabolomics and 16S rRNA gene sequencing to explore the relationship between the metabolic profile and the structure and function of gut microbiota. Striking alterations took place in 140 serum metabolites, as well as in the composition and function of rat gut microbiota. These changes were mainly associated with carbohydrate, lipid, and amino acid metabolism. In these pathways, isomaltose, D-mannose, galactonic acid, citramalic acid, and prostaglandin B2 were significantly upregulated. 3-(2-Hydroxyethyl)indole, 3-methylindole, and indoleacrylic acid were downregulated and were the critical metabolites in the DKD model. Furthermore, the levels of these three indoles were restored after treatment with the traditional Chinese herbal medicine Tangshen Formula. At the genera level, g_Eubacterium_nodatum_group, g_Lactobacillus, and g_Faecalibaculum were most involved in metabolic disorders in the progression of DKD. Notably, the circulating lipid metabolites had a strong relationship with DKD-related parameters and were especially negatively related to the mesangial matrix area. Serum lipid indices (TG and TC) and UACR were directly associated with certain microbial genera. In conclusion, the present research verified the anomalous circulating metabolites and gut microbiota in DKD progression. We also identified the potential metabolic and microbial targets for the treatment of DKD.https://www.frontiersin.org/articles/10.3389/fphar.2022.872988/fullgut microbiotadiabetic kidney diseasecarbohydrate metabolismlipid metabolismserum metabolitesamino acid metabolism |
| spellingShingle | Bo Zhang Bo Zhang Yuzhou Wan Xuefeng Zhou Haojun Zhang Hailing Zhao Liang Ma Xi Dong Meihua Yan Tingting Zhao Tingting Zhao Ping Li Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney Disease Frontiers in Pharmacology gut microbiota diabetic kidney disease carbohydrate metabolism lipid metabolism serum metabolites amino acid metabolism |
| title | Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney Disease |
| title_full | Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney Disease |
| title_fullStr | Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney Disease |
| title_full_unstemmed | Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney Disease |
| title_short | Characteristics of Serum Metabolites and Gut Microbiota in Diabetic Kidney Disease |
| title_sort | characteristics of serum metabolites and gut microbiota in diabetic kidney disease |
| topic | gut microbiota diabetic kidney disease carbohydrate metabolism lipid metabolism serum metabolites amino acid metabolism |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.872988/full |
| work_keys_str_mv | AT bozhang characteristicsofserummetabolitesandgutmicrobiotaindiabetickidneydisease AT bozhang characteristicsofserummetabolitesandgutmicrobiotaindiabetickidneydisease AT yuzhouwan characteristicsofserummetabolitesandgutmicrobiotaindiabetickidneydisease AT xuefengzhou characteristicsofserummetabolitesandgutmicrobiotaindiabetickidneydisease AT haojunzhang characteristicsofserummetabolitesandgutmicrobiotaindiabetickidneydisease AT hailingzhao characteristicsofserummetabolitesandgutmicrobiotaindiabetickidneydisease AT liangma characteristicsofserummetabolitesandgutmicrobiotaindiabetickidneydisease AT xidong characteristicsofserummetabolitesandgutmicrobiotaindiabetickidneydisease AT meihuayan characteristicsofserummetabolitesandgutmicrobiotaindiabetickidneydisease AT tingtingzhao characteristicsofserummetabolitesandgutmicrobiotaindiabetickidneydisease AT tingtingzhao characteristicsofserummetabolitesandgutmicrobiotaindiabetickidneydisease AT pingli characteristicsofserummetabolitesandgutmicrobiotaindiabetickidneydisease |