Circulating Gut Microbe-Derived Metabolites Are Associated with Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The gut microbiome has been implicated in outcomes for HCC, and gut microbe-derived products may serve as potential non-invasive indices for early HCC detection. This study evaluated differences in plasma concentrat...
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| Published in | Biomedicines Vol. 12; no. 9; p. 1946 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Switzerland
MDPI AG
01.09.2024
MDPI |
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| Online Access | Get full text |
| ISSN | 2227-9059 2227-9059 |
| DOI | 10.3390/biomedicines12091946 |
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| Abstract | Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The gut microbiome has been implicated in outcomes for HCC, and gut microbe-derived products may serve as potential non-invasive indices for early HCC detection. This study evaluated differences in plasma concentrations of gut microbiota-derived metabolites. Methods: Forty-one patients with HCC and 96 healthy controls were enrolled from surgical clinics at the Cleveland Clinic from 2016 to 2020. Gut microbiota-derived circulating metabolites detectable in plasma were compared between patients with HCC and healthy controls. Hierarchical clustering was performed for generating heatmaps based on circulating metabolite concentrations using ClustVis, with Euclidean and Ward settings and significant differences between metabolite concentrations were tested using a binary logistic regression model. Results: In patients with HCC, 25 (61%) had histologically confirmed cirrhosis. Trimethylamine (TMA)-related metabolites were found at higher concentrations in those with HCC, including choline (p < 0.001), betaine (p < 0.001), carnitine (p = 0.007), TMA (p < 0.001) and trimethylamine N-oxide (TMAO, p < 0.001). Notably, concentrations of P-cresol glucuronide (p < 0.001), indole-lactic acid (p = 0.038), 5-hydroxyindoleacetic acid (p < 0.0001) and 4-hydroxyphenyllactic acid (p < 0.001) were also increased in those with HCC compared to healthy controls. Hierarchical clustering of the metabolite panel separated patients based on the presence of HCC (p < 0.001), but was not able to distinguish between patients with HCC based on the presence of cirrhosis (p = 0.42). Conclusions: Gut microbiota-derived metabolites were differentially abundant in patients with HCC versus healthy controls. The observed perturbations of the TMAO pathway in HCC seem particularly promising as a target of future research and may have both diagnostic and therapeutic implications. |
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| AbstractList | Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The gut microbiome has been implicated in outcomes for HCC, and gut microbe-derived products may serve as potential non-invasive indices for early HCC detection. This study evaluated differences in plasma concentrations of gut microbiota-derived metabolites. Methods: Forty-one patients with HCC and 96 healthy controls were enrolled from surgical clinics at the Cleveland Clinic from 2016 to 2020. Gut microbiota-derived circulating metabolites detectable in plasma were compared between patients with HCC and healthy controls. Hierarchical clustering was performed for generating heatmaps based on circulating metabolite concentrations using ClustVis, with Euclidean and Ward settings and significant differences between metabolite concentrations were tested using a binary logistic regression model. Results: In patients with HCC, 25 (61%) had histologically confirmed cirrhosis. Trimethylamine (TMA)-related metabolites were found at higher concentrations in those with HCC, including choline (p < 0.001), betaine (p < 0.001), carnitine (p = 0.007), TMA (p < 0.001) and trimethylamine N-oxide (TMAO, p < 0.001). Notably, concentrations of P-cresol glucuronide (p < 0.001), indole-lactic acid (p = 0.038), 5-hydroxyindoleacetic acid (p < 0.0001) and 4-hydroxyphenyllactic acid (p < 0.001) were also increased in those with HCC compared to healthy controls. Hierarchical clustering of the metabolite panel separated patients based on the presence of HCC (p < 0.001), but was not able to distinguish between patients with HCC based on the presence of cirrhosis (p = 0.42). Conclusions: Gut microbiota-derived metabolites were differentially abundant in patients with HCC versus healthy controls. The observed perturbations of the TMAO pathway in HCC seem particularly promising as a target of future research and may have both diagnostic and therapeutic implications. Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The gut microbiome has been implicated in outcomes for HCC, and gut microbe-derived products may serve as potential non-invasive indices for early HCC detection. This study evaluated differences in plasma concentrations of gut microbiota-derived metabolites.Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The gut microbiome has been implicated in outcomes for HCC, and gut microbe-derived products may serve as potential non-invasive indices for early HCC detection. This study evaluated differences in plasma concentrations of gut microbiota-derived metabolites.Forty-one patients with HCC and 96 healthy controls were enrolled from surgical clinics at the Cleveland Clinic from 2016 to 2020. Gut microbiota-derived circulating metabolites detectable in plasma were compared between patients with HCC and healthy controls. Hierarchical clustering was performed for generating heatmaps based on circulating metabolite concentrations using ClustVis, with Euclidean and Ward settings and significant differences between metabolite concentrations were tested using a binary logistic regression model.METHODSForty-one patients with HCC and 96 healthy controls were enrolled from surgical clinics at the Cleveland Clinic from 2016 to 2020. Gut microbiota-derived circulating metabolites detectable in plasma were compared between patients with HCC and healthy controls. Hierarchical clustering was performed for generating heatmaps based on circulating metabolite concentrations using ClustVis, with Euclidean and Ward settings and significant differences between metabolite concentrations were tested using a binary logistic regression model.In patients with HCC, 25 (61%) had histologically confirmed cirrhosis. Trimethylamine (TMA)-related metabolites were found at higher concentrations in those with HCC, including choline (p < 0.001), betaine (p < 0.001), carnitine (p = 0.007), TMA (p < 0.001) and trimethylamine N-oxide (TMAO, p < 0.001). Notably, concentrations of P-cresol glucuronide (p < 0.001), indole-lactic acid (p = 0.038), 5-hydroxyindoleacetic acid (p < 0.0001) and 4-hydroxyphenyllactic acid (p < 0.001) were also increased in those with HCC compared to healthy controls. Hierarchical clustering of the metabolite panel separated patients based on the presence of HCC (p < 0.001), but was not able to distinguish between patients with HCC based on the presence of cirrhosis (p = 0.42).RESULTSIn patients with HCC, 25 (61%) had histologically confirmed cirrhosis. Trimethylamine (TMA)-related metabolites were found at higher concentrations in those with HCC, including choline (p < 0.001), betaine (p < 0.001), carnitine (p = 0.007), TMA (p < 0.001) and trimethylamine N-oxide (TMAO, p < 0.001). Notably, concentrations of P-cresol glucuronide (p < 0.001), indole-lactic acid (p = 0.038), 5-hydroxyindoleacetic acid (p < 0.0001) and 4-hydroxyphenyllactic acid (p < 0.001) were also increased in those with HCC compared to healthy controls. Hierarchical clustering of the metabolite panel separated patients based on the presence of HCC (p < 0.001), but was not able to distinguish between patients with HCC based on the presence of cirrhosis (p = 0.42).Gut microbiota-derived metabolites were differentially abundant in patients with HCC versus healthy controls. The observed perturbations of the TMAO pathway in HCC seem particularly promising as a target of future research and may have both diagnostic and therapeutic implications.CONCLUSIONSGut microbiota-derived metabolites were differentially abundant in patients with HCC versus healthy controls. The observed perturbations of the TMAO pathway in HCC seem particularly promising as a target of future research and may have both diagnostic and therapeutic implications. Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The gut microbiome has been implicated in outcomes for HCC, and gut microbe-derived products may serve as potential non-invasive indices for early HCC detection. This study evaluated differences in plasma concentrations of gut microbiota-derived metabolites. Forty-one patients with HCC and 96 healthy controls were enrolled from surgical clinics at the Cleveland Clinic from 2016 to 2020. Gut microbiota-derived circulating metabolites detectable in plasma were compared between patients with HCC and healthy controls. Hierarchical clustering was performed for generating heatmaps based on circulating metabolite concentrations using ClustVis, with Euclidean and Ward settings and significant differences between metabolite concentrations were tested using a binary logistic regression model. In patients with HCC, 25 (61%) had histologically confirmed cirrhosis. Trimethylamine (TMA)-related metabolites were found at higher concentrations in those with HCC, including choline ( < 0.001), betaine ( < 0.001), carnitine ( = 0.007), TMA ( < 0.001) and trimethylamine N-oxide (TMAO, < 0.001). Notably, concentrations of P-cresol glucuronide ( < 0.001), indole-lactic acid ( = 0.038), 5-hydroxyindoleacetic acid ( < 0.0001) and 4-hydroxyphenyllactic acid ( < 0.001) were also increased in those with HCC compared to healthy controls. Hierarchical clustering of the metabolite panel separated patients based on the presence of HCC ( < 0.001), but was not able to distinguish between patients with HCC based on the presence of cirrhosis ( = 0.42). Gut microbiota-derived metabolites were differentially abundant in patients with HCC versus healthy controls. The observed perturbations of the TMAO pathway in HCC seem particularly promising as a target of future research and may have both diagnostic and therapeutic implications. Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The gut microbiome has been implicated in outcomes for HCC, and gut microbe-derived products may serve as potential non-invasive indices for early HCC detection. This study evaluated differences in plasma concentrations of gut microbiota-derived metabolites. Methods: Forty-one patients with HCC and 96 healthy controls were enrolled from surgical clinics at the Cleveland Clinic from 2016 to 2020. Gut microbiota-derived circulating metabolites detectable in plasma were compared between patients with HCC and healthy controls. Hierarchical clustering was performed for generating heatmaps based on circulating metabolite concentrations using ClustVis, with Euclidean and Ward settings and significant differences between metabolite concentrations were tested using a binary logistic regression model. Results: In patients with HCC, 25 (61%) had histologically confirmed cirrhosis. Trimethylamine (TMA)-related metabolites were found at higher concentrations in those with HCC, including choline ( p < 0.001), betaine ( p < 0.001), carnitine ( p = 0.007), TMA ( p < 0.001) and trimethylamine N-oxide (TMAO, p < 0.001). Notably, concentrations of P-cresol glucuronide ( p < 0.001), indole-lactic acid ( p = 0.038), 5-hydroxyindoleacetic acid ( p < 0.0001) and 4-hydroxyphenyllactic acid ( p < 0.001) were also increased in those with HCC compared to healthy controls. Hierarchical clustering of the metabolite panel separated patients based on the presence of HCC ( p < 0.001), but was not able to distinguish between patients with HCC based on the presence of cirrhosis ( p = 0.42). Conclusions: Gut microbiota-derived metabolites were differentially abundant in patients with HCC versus healthy controls. The observed perturbations of the TMAO pathway in HCC seem particularly promising as a target of future research and may have both diagnostic and therapeutic implications. |
| Audience | Academic |
| Author | Tang, W. H. Wilson Wang, Zeneng Hazen, Stanley L. Mrdjen, Marko Varadharajan, Venkateshwari Lathia, Justin D. Aucejo, Federico Wehrle, Chase J. Reizes, Ofer Hershberger, Courtney Rotroff, Daniel M. Brown, J. Mark Banerjee, Rakhee Uppin, Vinayak Yu, Jennifer S. Wilcox, Jennifer D. |
| AuthorAffiliation | 7 Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44195, USA 9 Cleveland Clinic Foundation, Heart, Vascular and Thoracic Institute, Cleveland, OH 44195, USA 5 Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA; hershbc@ccf.org (C.H.); rotrofd@ccf.org (D.M.R.) 1 Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA; banerjr2@ccf.org (R.B.); vxu14@case.edu (V.U.); varadhv@ccf.org (V.V.); mrdjenm2@ccf.org (M.M.); yuj2@ccf.org (J.S.Y.) 6 Center for Quantitative Metabolic Research, Cleveland Clinic, Cleveland, OH 44195, USA 8 Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH 44195, USA 3 Department of Hepato-Pancreato-Biliary and Liver Transplant Surgery, Digestive Diseases and Surgery Institute, Cleveland Clinic, Cleveland, OH 44195, USA; wehrlec@ccf.org (C.J.W.); aucejof@ccf.org (F.A.) 4 Department of Cardiovascular and Metabolic Scie |
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| Keywords | nutrition metabolism microbiome cirrhosis hepatocellular carcinoma |
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