Metabolic Dysfunctions of Intestinal Fatty Acids and Tryptophan Reveal Immuno-Inflammatory Response Activation in IgA Nephropathy
BackgroundImmunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis. Although an important link between intestinal metabolites and immune activity is widely established, the metabolic profile of IgAN is still poorly understood, which severely limits the mechanistic st...
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Frontiers Media S.A.
2022-02-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.811526/full |
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| author | Hongwei Wu Hongwei Wu Hongwei Wu Donge Tang Manhua Yun Haiping Liu Shaoxing Huang Chen Yun Berthold Hocher Berthold Hocher Xinzhou Zhang Fanna Liu Lianghong Yin Yong Dai |
| author_facet | Hongwei Wu Hongwei Wu Hongwei Wu Donge Tang Manhua Yun Haiping Liu Shaoxing Huang Chen Yun Berthold Hocher Berthold Hocher Xinzhou Zhang Fanna Liu Lianghong Yin Yong Dai |
| author_sort | Hongwei Wu |
| collection | DOAJ |
| description | BackgroundImmunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis. Although an important link between intestinal metabolites and immune activity is widely established, the metabolic profile of IgAN is still poorly understood, which severely limits the mechanistic studies and therapy of IgAN.MethodsThe diversity of intestinal flora and relative abundance of metabolites in IgAN patients and healthy subjects were measured by 16s ribosomal RNA gene sequencing combined with liquid chromatography tandem-mass spectrometry. The levels of serum Gd-IgA1, IL-6, IL-10, IL-22, and TNF-a were tested by ELISA. We employed the tryptophan-targeted UHPLC-MRM-MS approach to assess the content of tryptophan metabolites quantitatively.ResultsIntestinal fatty acid levels, mainly unsaturated fatty acids, were observed to be dramatically decreased in IgAN patients. Disorders in linoleic acid and arachidonic acid metabolism, metabolic imbalances of anti-/pro- inflammatory fatty acid metabolites, and intestinal AhR signaling deficiency might reflect the damage of the intestinal mucosal barrier in IgAN patients. In addition, we found that high levels of Gd-IgA1, IL-22, and TNF-α were associated with the activity of the tryptophan-kynurenine metabolic pathway, as well as lower levels of 3-indolepropionic acid. 3-indolepropionic acid, kynurenine, and indoleacrylic acid had synergistic effects on regulating immuno-inflammatory responses in IgAN patients.ConclusionsThe metabolic characteristic of fatty acids and tryptophan in the intestinal system is disturbed in IgAN patients, leading to active immune-inflammatory reactions. |
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| last_indexed | 2024-04-11T19:37:01Z |
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| series | Frontiers in Medicine |
| spelling | doaj.art-1de60fc80acb4b6ab735ee1dfe8f17142022-12-22T04:06:50ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-02-01910.3389/fmed.2022.811526811526Metabolic Dysfunctions of Intestinal Fatty Acids and Tryptophan Reveal Immuno-Inflammatory Response Activation in IgA NephropathyHongwei Wu0Hongwei Wu1Hongwei Wu2Donge Tang3Manhua Yun4Haiping Liu5Shaoxing Huang6Chen Yun7Berthold Hocher8Berthold Hocher9Xinzhou Zhang10Fanna Liu11Lianghong Yin12Yong Dai13Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen Engineering Research Center of Autoimmune Disease, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, ChinaDepartment of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, ChinaDepartment of Medicine Nephrology, University Medical Centre Mannheim, Heidelberg, GermanyClinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen Engineering Research Center of Autoimmune Disease, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, ChinaDepartment of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, ChinaThe Second People's Hospital of Lianping County, Guangdong, ChinaThe Second People's Hospital of Lianping County, Guangdong, ChinaCharité -Universitätsmedizin Berlin, Berlin, GermanyDepartment of Medicine Nephrology, University Medical Centre Mannheim, Heidelberg, GermanyCharité -Universitätsmedizin Berlin, Berlin, GermanyKey Renal Laboratory of Shenzhen, Department of Nephrology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, ChinaDepartment of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, ChinaDepartment of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, ChinaClinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, Shenzhen Engineering Research Center of Autoimmune Disease, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, ChinaBackgroundImmunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis. Although an important link between intestinal metabolites and immune activity is widely established, the metabolic profile of IgAN is still poorly understood, which severely limits the mechanistic studies and therapy of IgAN.MethodsThe diversity of intestinal flora and relative abundance of metabolites in IgAN patients and healthy subjects were measured by 16s ribosomal RNA gene sequencing combined with liquid chromatography tandem-mass spectrometry. The levels of serum Gd-IgA1, IL-6, IL-10, IL-22, and TNF-a were tested by ELISA. We employed the tryptophan-targeted UHPLC-MRM-MS approach to assess the content of tryptophan metabolites quantitatively.ResultsIntestinal fatty acid levels, mainly unsaturated fatty acids, were observed to be dramatically decreased in IgAN patients. Disorders in linoleic acid and arachidonic acid metabolism, metabolic imbalances of anti-/pro- inflammatory fatty acid metabolites, and intestinal AhR signaling deficiency might reflect the damage of the intestinal mucosal barrier in IgAN patients. In addition, we found that high levels of Gd-IgA1, IL-22, and TNF-α were associated with the activity of the tryptophan-kynurenine metabolic pathway, as well as lower levels of 3-indolepropionic acid. 3-indolepropionic acid, kynurenine, and indoleacrylic acid had synergistic effects on regulating immuno-inflammatory responses in IgAN patients.ConclusionsThe metabolic characteristic of fatty acids and tryptophan in the intestinal system is disturbed in IgAN patients, leading to active immune-inflammatory reactions.https://www.frontiersin.org/articles/10.3389/fmed.2022.811526/fullIgA nephropathyfatty acid metabolismtryptophan metabolismimmune3-indolepropionic acid |
| spellingShingle | Hongwei Wu Hongwei Wu Hongwei Wu Donge Tang Manhua Yun Haiping Liu Shaoxing Huang Chen Yun Berthold Hocher Berthold Hocher Xinzhou Zhang Fanna Liu Lianghong Yin Yong Dai Metabolic Dysfunctions of Intestinal Fatty Acids and Tryptophan Reveal Immuno-Inflammatory Response Activation in IgA Nephropathy Frontiers in Medicine IgA nephropathy fatty acid metabolism tryptophan metabolism immune 3-indolepropionic acid |
| title | Metabolic Dysfunctions of Intestinal Fatty Acids and Tryptophan Reveal Immuno-Inflammatory Response Activation in IgA Nephropathy |
| title_full | Metabolic Dysfunctions of Intestinal Fatty Acids and Tryptophan Reveal Immuno-Inflammatory Response Activation in IgA Nephropathy |
| title_fullStr | Metabolic Dysfunctions of Intestinal Fatty Acids and Tryptophan Reveal Immuno-Inflammatory Response Activation in IgA Nephropathy |
| title_full_unstemmed | Metabolic Dysfunctions of Intestinal Fatty Acids and Tryptophan Reveal Immuno-Inflammatory Response Activation in IgA Nephropathy |
| title_short | Metabolic Dysfunctions of Intestinal Fatty Acids and Tryptophan Reveal Immuno-Inflammatory Response Activation in IgA Nephropathy |
| title_sort | metabolic dysfunctions of intestinal fatty acids and tryptophan reveal immuno inflammatory response activation in iga nephropathy |
| topic | IgA nephropathy fatty acid metabolism tryptophan metabolism immune 3-indolepropionic acid |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.811526/full |
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