Microbial Oncotarget: Bacterial-Produced Butyrate, Chemoprevention and Warburg Effect

Donohoe, Dallas R.; Curry, Kaitlin P.; Bultman, Scott J.

doi:10.18632/oncotarget.915

Cited by 19 publications

(13 citation statements)

References 9 publications

(9 reference statements)

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“… 139 Interestingly, the anti-carcinogenic effect of butyrate is dose-dependent; a lower concentration of the butyrate (0.5–1 mM) promotes growth of non-cancerous colonocytes and apoptosis in cancerous ones, whereas at higher concentrations (greater than 2 mM) it can cause apoptosis in both. 140 , 141 Indeed, butyrate induces proliferation of colonocytes at the cript of the colon, where its concentration is lower, but shows a pro-apoptotic effect closer to the lumen where its concentration increases; this also ensures normal turnover of cells in the intestine. 142 …”

Section: Short-chain Fatty Acids Produced By Eubacterium mentioning

confidence: 99%

Gut microbes from the phylogenetically diverse genusEubacteriumand their various contributions to gut health

et al. 2020

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Over the last two decades our understanding of the gut microbiota and its contribution to health and disease has been transformed. Among a new 'generation' of potentially beneficial microbes to have been recognized are members of the genus Eubacterium, who form a part of the core human gut microbiome. The genus consists of phylogenetically, and quite frequently phenotypically, diverse species, making Eubacterium a taxonomically unique and challenging genus. Several members of the genus produce butyrate, which plays a critical role in energy homeostasis, colonic motility, immunomodulation and suppression of inflammation in the gut. Eubacterium spp. also carry out bile acid and cholesterol transformations in the gut, thereby contributing to their homeostasis. Gut dysbiosis and a consequently modified representation of Eubacterium spp. in the gut, have been linked with various human disease states. This review provides an overview of Eubacterium species from a phylogenetic perspective, describes how they alter with diet and age and summarizes its association with the human gut and various health conditions.

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Section: Short-chain Fatty Acids Produced By Eubacterium mentioning

confidence: 99%

Gut microbes from the phylogenetically diverse genusEubacteriumand their various contributions to gut health

et al. 2020

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“…However, the HDAC inhibition mechanism (i.e., ACL independent) became more prevalent at 2 mM and was the prominent one at 5 mM, accounting for 75% of the upregulated genes. This mechanistic shift can be explained by the observation that these cells reach their oxidative metabolic capacity at 1–2 mM doses of butyrate (30, 31). Therefore, when the dosage exceeds this range, butyrate molecules are not metabolized in the mitochondria and accumulate as HDAC inhibitors in the nucleus.…”

Section: Butyrate Increases Histone Acetylation By Two Distinct Mechamentioning

confidence: 99%

Molecular Pathways: Gene–Environment Interactions Regulating Dietary Fiber Induction of Proliferation and Apoptosis via Butyrate for Cancer Prevention

Bultman

2014

Clinical Cancer Research

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125

106

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Gene-environment interactions are so numerous and biologically complicated that it can be challenging to understand their role in cancer. However, dietary fiber and colorectal cancer prevention may represent a tractable model system. Fiber is fermented by colonic bacteria into short-chain fatty acids such as butyrate. One molecular pathway that has emerged involves butyrate having differential effects depending on its concentration and the metabolic state of the cell. Low-moderate concentrations, which are present near the base of colonic crypts, are readily metabolized in the mitochondria to stimulate cell proliferation via energetics. Higher concentrations, which are present near the lumen, exceed the metabolic capacity of the colonocyte. Unmetabolized butyrate enters the nucleus and functions as a histone deacetylase (HDAC) inhibitor that epigenetically regulates gene expression to inhibit cell proliferation and induce apoptosis as the colonocytes exfoliate into the lumen. Butyrate may therefore play a role in normal homeostasis by promoting turnover of the colonic epithelium. Because cancerous colonocytes undergo the Warburg effect, their preferred energy source is glucose instead of butyrate. Consequently, even moderate concentrations of butyrate accumulate in cancerous colonocytes and function as HDAC inhibitors to inhibit cell proliferation and induce apoptosis. These findings implicate a bacterial metabolite with metaboloepigenetic properties in tumor suppression.

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“…Butyrate is the preferred substrate of colonocytes [43]. This compost was incredibly studied due to its capacity to reduce oxidative stress, diminish inflammation and carcinogenesis, and support colonic barrier function [44].…”

Section: Dietmentioning

confidence: 99%

Immunoscore and Microbiome in Colorectal Cancer: What’s New?

Macedo¹,

Bonito²,

Longatto‐Filho³

et al. 2019

Multidisciplinary Approach for Colorectal Cancer

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Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the fourth leading cause of cancer death in the world, accounting for about 1.4 million new cases and almost 700,000 deaths in 2012. The clinical outcome and the tumor progression are now considered the result of a balance between the invasiveness of the tumor and the immune response of the patient against the tumor. The immune system has the ability to control and shape cancer through a mechanism called immunoediting, which include elimination, equilibrium, and escape. The consensus Immunoscore is a scoring system that outlines the density of CD3+ and CD8+ T-cell effectors existent in the tumor and its invasive margin. The pre-existing intra-tumoral immunity could be enhanced and activated by immunotherapy. Immunoscore could be a good prognostic marker, by identifying patients at high risk of tumor recurrence and stratifying patients who could benefit from adjuvant therapies. Human surfaces and cavities are populated by numerous microbial communities, and they play an indispensable role in human health, as they interact with the immune system. The authors made a literature revision concerning the role of Immunoscore and microbiome in colorectal cancer.

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Microbial Oncotarget: Bacterial-Produced Butyrate, Chemoprevention and Warburg Effect

Cited by 19 publications

References 9 publications

Gut microbes from the phylogenetically diverse genusEubacteriumand their various contributions to gut health

Gut microbes from the phylogenetically diverse genusEubacteriumand their various contributions to gut health

Molecular Pathways: Gene–Environment Interactions Regulating Dietary Fiber Induction of Proliferation and Apoptosis via Butyrate for Cancer Prevention

Immunoscore and Microbiome in Colorectal Cancer: What’s New?

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