Role of gut microbiome in regulating the effectiveness of metformin in reducing colorectal cancer in type 2 diabetes

Huang, Qiyou; Yao, Fei; Zhou, Chuanren; Huang, Xiaoying; Wang, Qiang; Long, Hui; Wu, Qingming

doi:10.12998/wjcc.v8.i24.6213

Cited by 13 publications

(9 citation statements)

References 93 publications

(48 reference statements)

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“…136, 137 Metformin interacts with F. nucleatum by reducing its levels and antagonizing the progression of CRC. 138 Beyond reducing the levels of this strain, metformin is associated with the inhibition of the TLR4/MYD88/NF-ΚB pathway, 139 thus reducing the inflammation and metastasis in CRC (Fig. 1).…”

Section: Metformin and Colorectal Cancer (Crc)mentioning

confidence: 99%

Metformin, Microbiota and Health

Paz¹,

Fernandes²

2022

J Explor Res Pharmacol

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Microbiota and its role in the human bodyMicrobiota, whose composition and activity are associated with health and the development of diseases, 1 are composed of different microorganisms, including bacteria, bacteriophages, eukaryotic viruses, and fungi that inhabit body surfaces and cavities usually in a beneficial relationship for both parties. 2 Most microbiotás microorganisms are found in the gastrointestinal tract (mainly colon), and their composition are influenced by the type of birth, lifestyle, diet in the first years of life, medications, and host genetics. 2 Human microbiota composition comprises approximately 1,000 species, where bacteria are considered the main constituents corresponding to the five main phyla: Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, and Verrucomicrobia. 3 Studies have pointed out that the number of these microbial cells is around 1 × 10 14 against 1 × 10 13 of eukaryotic cells, thus indicating that the number of microbial cells is 10 times greater than the number of human cells. 4 Hence, the microbiota can be considered as a metabolic organ supporting important functions in the host, such as digestion and absorption of food nutrients, the regulation of the immune system, regulation of the endocrine and neurological functions, alteration of the mechanism of the action of drugs, removing toxins, and the production of various compounds, including vitamins and short chain fatty acids (SC-FAs). 2,5 The maintenance of diverse microbiota with a functionally stable microbiome contributes to the homeostasis and health of the host. 6 Modulations in the composition of the microbiota, compromising the symbiotic relationship between the host and microorganisms in a process called dysbiosis, are often associated with the development of autoimmune diseases, obesity, diabetes, cancers, neurological diseases among others. 7,8 Dysbiosis can be classified into three types: (1) loss of beneficial microorganisms, (2) an increase in opportunistic pathogens, and (3) loss of microbiota diversity; despite this categorization, the three scenarios usually occur simultaneously. 9 Thus, factors capable of promoting changes in the composition of the microbiota are considered risk factors for diseases associated with a microbial imbalance. 9 Therefore, drugs able to restore the microbiota balance have become promising candidates for the treatment of these pathologies. In this context, metformin is an important candidate, so are several factors that regulate its uptake and activity. Metformin: Brief history and the main mechanisms of actionMetformin (1,1-dimethylbiguanide) is a drug of the biguanide class derived from guanidine, the active substance in Galega officinalis. The processes for its synthesis began in 1920, from the discovery of the antidiabetic properties in 1918 of guanidine. 10 Due to its high antihyperglycemic efficiency, without causing

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Section: Metformin and Colorectal Cancer (Crc)mentioning

confidence: 99%

Metformin, Microbiota and Health

Paz¹,

Fernandes²

2022

J Explor Res Pharmacol

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“…Metformin inhibits CRC in T2D patients by altering the abundance of gut microbiota or involving gut microbiota. 113 Metformin can also inhibit microglial activation and neuroinflammation in the brain by regulating intestinal flora in obese mice and thus may be considered a promising candidate for the intervention of cognitive decline related to an obesity-induced imbalance of the gut microbiota. 114 However, due to the complex composition of microbial communities, considerable differences in species, individuals and experimental design, the changes in gut microbes caused by metformin are not consistent, which presents great obstacles for us to better understand the relationship between metformin and gut microbes.…”

Section: Anti-aging Interventions and Intestinal Microbesmentioning

confidence: 99%

Effects of anti-aging interventions on intestinal microbiota

Gao

Zeng

et al. 2021

Gut Microbes

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“…Anti-diabetic drug such as metformin produced significant changes in the gut microbiome of CRC patients with type 2 diabetes mellitus (T2DM). Comparative analysis among CRC patients with T2DM showed that metformin was associated with increase in Firmicutes and decrease in Bacteroidetes and Fusobacteria at the phyla level, while Bifidobacterium increased at genus level, whereas the abundance of pro-tumorigenic species F. nucleatum was decreased ( 30 ). Metformin treatment in T2DM has shown to increase the gut bacteria associated with enhanced production of SCFA such as butyrate and propionate which improve glucose metabolism and homeostasis ( 31 ).…”

Section: Gut Microbiome and Colorectal Cancermentioning

confidence: 99%

“…Anti-diabetic drugs such as metformin induces changes in the gut microbiome of T2DM patients developing CRC. Comparative analysis showed that initiation of metformin in T2DM patients with CRC was associated with an increase in Firmicutes and decrease in Bacteroidetes and Fusobacteria at the phyla level while at genus level increase in Bifidobacterium with an associated decrease in F. nucleatum ( 30 ). Metformin treatment of T2DM has shown to enhance the microbial richness of the colon associated with enhanced production of SCFAs such as butyrate and propionate which potentially improves glucose metabolism and homeostasis ( 31 ).…”

Section: Gut Microbiome and Colorectal Cancermentioning

confidence: 99%

Emerging Evidence on the Effects of Dietary Factors on the Gut Microbiome in Colorectal Cancer

et al. 2021

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Dietary factors have important role in modulating the gut microbiome, which in-turn regulates the molecular events in colonic mucosa. The composition and resulting metabolism of the gut microbiome are decisive factors in colorectal cancer (CRC) tumorigenesis. Altered gut microbiome is associated with impaired immune response, and the release of carcinogenic or genotoxic substances which are the major microbiome-induced mechanisms implicated in CRC pathogenesis. Diets low in dietary fibers and phytomolecules as well as high in red meat are important dietary changes which predispose to CRC. Dietary fibers which reach the colon in an undigested form are further metabolized by the gut microbiome into enterocyte friendly metabolites such as short chain fatty acid (SCFA) which provide anti-inflammatory and anti-proliferative effects. Healthy microbiome supported by dietary fibers and phytomolecules could decrease cell proliferation by regulating the epigenetic events which activate proto-oncogenes and oncogenic pathways. Emerging evidence show that predominance of microbes such as Fusobacterium nucleatum can predispose the colonic mucosa to malignant transformation. Dietary and lifestyle modifications have been demonstrated to restrict the growth of potentially harmful opportunistic organisms. Synbiotics can protect the intestinal mucosa by improving immune response and decreasing the production of toxic metabolites, oxidative stress and cell proliferation. In this narrative review, we aim to update the emerging evidence on how diet could modulate the gut microbial composition and revive colonic epithelium. This review highlights the importance of healthy plant-based diet and related supplements in CRC prevention by improving the gut microbiome.

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Role of gut microbiome in regulating the effectiveness of metformin in reducing colorectal cancer in type 2 diabetes

Cited by 13 publications

References 93 publications

Metformin, Microbiota and Health

Metformin, Microbiota and Health

Effects of anti-aging interventions on intestinal microbiota

Emerging Evidence on the Effects of Dietary Factors on the Gut Microbiome in Colorectal Cancer

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