Contributions of Human-Associated Archaeal Metabolites to Tumor Microenvironment and Carcinogenesis

Cai, Mingwei; Kandalai, Shruthi; Tang, Xiaoyu; Zheng, Qingfei

doi:10.1128/spectrum.02367-21

Cited by 16 publications

(13 citation statements)

References 88 publications

(122 reference statements)

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“…Phylum Euryarchaeota , as an archaea may produce cancer-related metabolites that contribute to the human tumour microenvironment and carcinogenesis. This is consistent with our findings of a positive correlation between phylum Euryarchaeota and CA-125 ( Cai et al., 2022 ). CSF-1 stimulates macrophage colonization and granulocyte function, and lowers blood cholesterol ( Hume and MacDonald, 2012 ).…”

Section: Discussionsupporting

confidence: 93%

Causal relationship between gut microbes and cardiovascular protein expression

Zhang

Zhang²,

Zhang³

et al. 2022

Front. Cell. Infect. Microbiol.

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Evidence supports associations between gut microbiota and cardiovascular protein levels in plasma. However, it is unclear whether these associations reflect a causal relationship. To reveal the causal relationship between gut microbiota and cardiovascular protein levels in plasma, we estimated their causal effects using two-sample Mendelian randomization (MR) analysis. Sensitivity analysis was also performed to assess the robustness of our results. Genome-wide association study (GWAS) of microbiomes in the MiBioGen study included 211 bacterial taxa (18,473 individuals), and GWAS of 90 cardiovascular proteins included 30,931 individuals. There were 196 bacterial taxa from five levels available for analysis. The following 14 causal relationships were identified: phylum Euryarchaeota and carbohydrate antigen 125 (β = 0.289), order Bacillales and CSF-1 (β = -0.211), genus Dorea and HSP-27 (β = 0.465), phylum Actinobacteria and IL-8 (β = 0.274), order Enterobacteriales and KIM-1 (β = -0.499), class Actinobacteria, genus Bifidobacterium, phylum Actinobacteria and LEP (β = -0.219, β = -0.201, and β = -0.221), genus Methanobrevibacter and NT-proBNP (β = 0.371), family Peptostreptococcaceae and SRC (β = 0.191), order Verrucomicrobiales, phylum Verrucomicrobia and TNF-R2 (β = 0.251 and β = 0.233), family Veillonellaceae and t-PA (β = 0.271), and class Erysipelotrichia and VEGF-D (β = 0.390). Sensitivity analysis showed no evidence of pleiotropy or heterogeneity. The results of the reverse MR analysis showed no reverse causality for any of the 13 gut microbes and 11 cardiovascular proteins. Mendelian randomization estimates provide strong evidence for a causal effect of gut microbiota-mediated alterations on cardiovascular protein expression.

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Section: Discussionsupporting

confidence: 93%

Causal relationship between gut microbes and cardiovascular protein expression

Zhang

Zhang²,

Zhang³

et al. 2022

Front. Cell. Infect. Microbiol.

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“…There are growing evidence that archaea are involved in human cancers [176]. Archaea produces a variety of metabolites by utilizing unique metabolic pathways, and cancer-related metabolites (such as polyamines and SCFAs) of archaea are prevalent and diverse in oral and gut, which are mainly related to the TACK superphylum and Euryarchaeota, especially methanogenic archaea [177]. However, there are very few studies to elucidate how archaea regulate cancer treatment up to now.…”

Section: Modulation Of Gut Microbiota For Gi Cancermentioning

confidence: 99%

Gut microbiome in gastrointestinal cancer: a friend or foe?

Liu¹,

Baba²,

Ishimoto³

et al. 2022

Int. J. Biol. Sci.

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The impact of the gut microbiome on host health is becoming increasingly recognized. To date, there is growing evidence that the complex characteristics of the microbial community play key roles as potential biomarkers and predictors of responses in cancer therapy. Many studies have shown that altered commensal bacteria lead to cancer susceptibility and progression in diverse pathways. In this review, we critically assess the data for gut microbiota related to gastrointestinal cancer, including esophageal, gastric, pancreatic, colorectal cancer, hepatocellular carcinoma and cholangiocarcinoma. Importantly, the underlying mechanisms of gut microbiota involved in cancer occurrence, prevention and treatment are elucidated. The purpose of this review is to provide novel insights for applying this understanding to the development of new therapeutic strategies in gastrointestinal cancer by targeting the microbial community.

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“…There are a number of primary metabolites produced by microbes that contribute to cancer development or suppression, such as methylglyoxal (MGO), SCFAs, BAs, reactive oxygen species (ROS), amines, and methane (CH 4 ) ( 85 – 87 ). These molecules are biosynthesized by diverse human-associated microorganisms, including archaea ( 88 ), bacteria ( 89 , 90 ), fungi ( 90 ) protists ( 91 ) and parasites ( 91 , 92 ).…”

Section: Metabolites Produced By Tumor Microbiomementioning

confidence: 99%

“…MGO is a chemically reactive dicarbonyl metabolite of glucose metabolism ( 155 , 156 ). In mammalian cells, MGO is mainly generated as a byproduct through a non-enzymatic dephosphorylation process during glycolysis, although it can also be produced by tumor microbes that contain microorganism-specific methylglyoxal synthases ( 88 , 157 ). MGO can react with nucleophilic groups of biomacromolecules, such as lysine and arginine residues in proteins ( 158 ), as well as guanine residues in DNA and RNA ( 159 ).…”

Section: Impacts Of Tumor Microbiome Metabolites On Cancer Developmentmentioning

confidence: 99%

Tumor microbiome metabolism: A game changer in cancer development and therapy

et al. 2022

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Accumulating recent evidence indicates that the human microbiome plays essential roles in pathophysiological states, including cancer. The tumor microbiome, an emerging concept that has not yet been clearly defined, has been proven to influence both cancer development and therapy through complex mechanisms. Small molecule metabolites produced by the tumor microbiome through unique biosynthetic pathways can easily diffuse into tissues and penetrate cell membranes through transporters or free diffusion, thus remodeling the signaling pathways of cancer and immune cells by interacting with biomacromolecules. Targeting tumor microbiome metabolism could offer a novel perspective for not only understanding cancer progression but also developing new strategies for the treatment of multiple cancer types. Here, we summarize recent advances regarding the role the tumor microbiome plays as a game changer in cancer biology. Specifically, the metabolites produced by the tumor microbiome and their potential effects on the cancer development therapy are discussed to understand the importance of the microbial metabolism in the tumor microenvironment. Finally, new anticancer therapeutic strategies that target tumor microbiome metabolism are reviewed and proposed to provide new insights in clinical applications.

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Contributions of Human-Associated Archaeal Metabolites to Tumor Microenvironment and Carcinogenesis

Abstract: More evidence suggests that archaea are associated with human disease, including cancer. Here, we present the first framework of the diversity and distribution of human-associated archaea across human body sites, such as gut and oral cavity, using long contigs.

Cited by 16 publications

References 88 publications

Causal relationship between gut microbes and cardiovascular protein expression

Causal relationship between gut microbes and cardiovascular protein expression

Gut microbiome in gastrointestinal cancer: a friend or foe?

Tumor microbiome metabolism: A game changer in cancer development and therapy

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