Association between Levels of Trimethylamine N-Oxide and Cancer: A Systematic Review and Meta-Analysis

Khodabakhshi, Adeleh; Monfared, Vahid; Arabpour, Zahra; Vahid, Farhad; Hasani, Motahareh

doi:10.1080/01635581.2022.2129080

Cited by 5 publications

(5 citation statements)

References 55 publications

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“…TMAO is anticipated to have significance as a biomarker of—or even an independent risk factor for UGC (Oellgaard et al 2017 ). More studies confirmed the association of microbiota with TMAO production, resulting in higher risk of colorectal, breast, and gastric cancer (Khodabakhshi et al 2023 ). Another metabolite in this heterogenous field is the polyamine putrescine, a polycationic alkylamine commonly found in all living cells and essential for cellular growth and survival.…”

Section: Discussionmentioning

confidence: 87%

Metabolomic profiling of upper GI malignancies in blood and tissue: a systematic review and meta-analysis

Balonov,

Mattis,

Jarmusch

et al. 2024

J Cancer Res Clin Oncol

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Objective To conduct a systematic review and meta-analysis of case–control and cohort human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on esophageal cancer (EC), cancer of the gastroesophageal junction (GEJ), and gastric cancer (GC) in blood and tissue. Background Upper gastrointestinal cancers (UGC), predominantly EC, GEJ, and GC, are malignant tumour types with high morbidity and mortality rates. Numerous studies have focused on metabolomic profiling of UGC in recent years. In this systematic review and meta-analysis, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with EC, GEJ and GC. Methods Following the PRISMA procedure, a systematic search of four databases (Embase, PubMed, MEDLINE, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of EC, GEJ and GC was conducted and registered at PROSPERO (CRD42023486631). The Newcastle–Ottawa Scale (NOS) was used to benchmark the risk of bias for case-controlled and cohort studies. QUADOMICS, an adaptation of the QUADAS-2 (Quality Assessment of Diagnostic Accuracy) tool, was used to rate diagnostic accuracy studies. Original articles comparing metabolite patterns between patients with and without UGC were included. Two investigators independently completed title and abstract screening, data extraction, and quality evaluation. Meta-analysis was conducted whenever possible. We used a random effects model to investigate the association between metabolite levels and UGC. Results A total of 66 original studies involving 7267 patients that met the required criteria were included for review. 169 metabolites were differentially distributed in patients with UGC compared to healthy patients among 44 GC, 9 GEJ, and 25 EC studies including metabolites involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and lipid metabolism. Phosphatidylcholines, eicosanoids, and adenosine triphosphate were among the most frequently reported lipids and metabolites of cellular respiration, while BCAA, lysine, and asparagine were among the most commonly reported amino acids. Previously identified lipid metabolites included saturated and unsaturated free fatty acids and ketones. However, the key findings across studies have been inconsistent, possibly due to limited sample sizes and the majority being hospital-based case–control analyses lacking an independent replication group. Conclusion Thus far, metabolomic studies have provided new opportunities for screening, etiological factors, and biomarkers for UGC, supporting the potential of applying metabolomic profiling in early cancer diagnosis. According to the results of our meta-analysis especially BCAA and TMAO as well as certain phosphatidylcholines should be implicated into the diagnostic procedure of patients with UGC. We envision that metabolomics will significantly enhance our understanding of the carcinogenesis and progression process of UGC and may eventually facilitate precise oncological and patient-tailored management of UGC.

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Section: Discussionmentioning

confidence: 87%

Metabolomic profiling of upper GI malignancies in blood and tissue: a systematic review and meta-analysis

Balonov,

Mattis,

Jarmusch

et al. 2024

J Cancer Res Clin Oncol

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“…This finding was confirmed in another study conducted by Clara E et al where a higher colonic abundance of Firmicutes and Bacteroidetes in men was associated with an increase in blood TMAO levels after ingestion of its precursors, choline or carnitine, demonstrating the role of microbiota in determining how L-carnitine is further processed by microorganisms [ 54 ]. More studies confirmed the association of microbiota with TMAO production resulting in higher colorectal, breast, and gastric cancer risks [ 55 ]. Gut microbiota composition is a very sensitive entity that can be influenced by various factors that include gender, metabolic state and comorbidities.…”

Section: Discussionmentioning

confidence: 91%

The Association of Circulating L-Carnitine, γ-Butyrobetaine and Trimethylamine N-Oxide Levels with Gastric Cancer

et al. 2023

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Our study aimed to evaluate the association between gastric cancer (GC) and higher concentrations of the metabolites L-carnitine, γ-butyrobetaine (GBB) and gut microbiota-mediated trimethylamine N-oxide (TMAO) in the circulation. There is evidence suggesting that higher levels of TMAO and its precursors in blood can be indicative of either a higher risk of malignancy or indeed its presence; however, GC has not been studied in this regard until now. Our study included 83 controls without high-risk stomach lesions and 105 GC cases. Blood serum L-carnitine, GBB and TMAO levels were measured by ultra-high-performance liquid chromatography–mass spectrometry (UPLC/MS/MS). Although there were no significant differences between female control and GC groups, we found a significant difference in circulating levels of metabolites between the male control group and the male GC group, with median levels of L-carnitine reaching 30.22 (25.78–37.57) nmol/mL vs. 37.38 (32.73–42.61) nmol/mL (p < 0.001), GBB–0.79 (0.73–0.97) nmol/mL vs. 0.97 (0.78–1.16) nmol/mL (p < 0.05) and TMAO–2.49 (2.00–2.97) nmol/mL vs. 3.12 (2.08–5.83) nmol/mL (p < 0.05). Thus, our study demonstrated the association between higher blood levels of L-carnitine, GBB, TMAO and GC in males, but not in females. Furthermore, correlations of any two investigated metabolites were stronger in the GC groups of both genders in comparison to the control groups. Our findings reveal the potential role of L-carnitine, GBB and TMAO in GC and suggest metabolic differences between genders. In addition, the logistic regression analysis revealed that the only significant factor in terms of predicting whether the patient belonged to the control or to the GC group was the blood level of L-carnitine in males only. Hence, carnitine might be important as a biomarker or a risk factor for GC, especially in males.

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“…Owing to its proinflammatory and proinsulin resistance properties, TMAO has been postulated to be a key mediator for the relation among diet, gut microbiota, and various health conditions, including cardiovascular disease, type 2 diabetes, and CRC 41,47,48 . A recent systemic review and meta-analysis on TMAO and cancer incidence reported the summary OR of 9 studies to be 1.64 (95% CI, 1.35–1.99) per an increase in serum/plasma TMAO concentrations for all cancers combined, although it was not clear how effect sizes were standardized across the studies 49 . Among those included, 4 were CRC studies, and 2 of them were from prospective cohort studies, 49 supporting the potential link.…”

Section: Emerging Microbial Metabolites Of Dietary Component and Crc ...mentioning

confidence: 99%

“…A recent systemic review and meta-analysis on TMAO and cancer incidence reported the summary OR of 9 studies to be 1.64 (95% CI, 1.35–1.99) per an increase in serum/plasma TMAO concentrations for all cancers combined, although it was not clear how effect sizes were standardized across the studies 49 . Among those included, 4 were CRC studies, and 2 of them were from prospective cohort studies, 49 supporting the potential link.…”

Section: Emerging Microbial Metabolites Of Dietary Component and Crc ...mentioning

confidence: 99%

Microbiome and Diet in Colon Cancer Development and Treatment

Kato

Sun

2023

Cancer J

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Diet plays critical roles in defining our immune responses, microbiome, and progression of human diseases. With recent progress in sequencing and bioinformatic techniques, increasing evidence indicates the importance of diet-microbial interactions in cancer development and therapeutic outcome. Here, we focus on the epidemiological studies on diet-bacterial interactions in the colon cancer. We also review the progress of mechanistic studies using the experimental models. Finally, we discuss the limits and future directions in the research of microbiome and diet in cancer development and therapeutic outcome. Now, it is clear that microbes can influence the efficacy of cancer therapies. These research results open new possibilities for the diagnosis, prevention, and treatment of cancer. However, there are still big gaps to apply these new findings to the clinical practice.

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Association between Levels of Trimethylamine N-Oxide and Cancer: A Systematic Review and Meta-Analysis

Cited by 5 publications

References 55 publications

Metabolomic profiling of upper GI malignancies in blood and tissue: a systematic review and meta-analysis

Metabolomic profiling of upper GI malignancies in blood and tissue: a systematic review and meta-analysis

The Association of Circulating L-Carnitine, γ-Butyrobetaine and Trimethylamine N-Oxide Levels with Gastric Cancer

Microbiome and Diet in Colon Cancer Development and Treatment

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