Canmei Formula Reduces Colitis-Associated Colorectal Carcinogenesis in Mice by Modulating the Composition of Gut Microbiota

Zhang, Hua yue; Hui, Deng; Li, Yuan; Xiong, Guang su; Fu, Xiao Ling

doi:10.3389/fonc.2019.01149

Cited by 23 publications

(15 citation statements)

References 37 publications

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“…This formulation was shown to decrease the incidence of colonic tumors by reducing inflammation and improving dysbiosis. 137 Another study using a Boswellia serrata resin extract has also demonstrated, in preclinical models, its ability to reduce colonic tumor formation. 144 Many of these studies present positive results for the inhibition of CRC development.…”

Section: Discussionmentioning

confidence: 98%

Colorectal cancer and microbiota modulation for clinical use. A systematic review

Madrigal‐Matute¹,

Banon-Escandell²

2021

Preprint

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Colorectal cancer is one of the top contributors to the global burden of cancer incidence and mortality with genetic and environmental factors contributing to its etiology. Modifiable or environmental factors can be the cause of up to 60% of the risk of developing colorectal cancer. Hence, there is a growing interest in specifically defining what can be improved in our lifestyle to reduce this risk, improve the effectiveness of treatments, reduce side effects, and decrease the risk of recurrence. One of the elements directly related to lifestyle is gut microbiota. The microbial ecosystem has a vital role in colorectal cancer prevention and antitumoral response through modulation of the immune system and production of short-chain fatty acids. Numerous approaches have been used to identify healthy microbiota that can reduce the risk of cancer development, improve treatment efficacy, and reduce side effects. Scientific literature in this subject is growing exponentially and, therefore, systematic reviews and meta-analysis are required to ensure that appropriate recommendations are given to patients. This work aimed to perform a systematic analysis of the published literature to elucidate whether microbiota modulation through pre-, pro-, symbiotic treatment and/or nutritional intervention can be beneficial for patients diagnosed with colorectal cancer. Detailed analysis of published studies shows that some prebiotics, such as inulin and resistant starch, probiotics such as lactic strains producers of short-chain fatty acids, and consumption of unprocessed plant products, can be effective recommendations for patients diagnosed with colorectal cancer. This advice should always be individually tailored and followed up by a healthcare professional with expertise in the field.

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Section: Discussionmentioning

confidence: 98%

Colorectal cancer and microbiota modulation for clinical use. A systematic review

Madrigal‐Matute¹,

Banon-Escandell²

2021

Preprint

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“… 19 Another TCM formula, CanMei formula, was found to upregulate the abundance of the genera Alistipes, Faecalibaculum, Lactobacillus , and Parabacterioides , while decreasing Desulfovibrionacea in colitis-associated colorectal tumor model mice, which might be associated with suppression of IL-17C and NF-κB to prevent CRC development. 20 Yang et al found that Ganoderma Lingzhi, a TCM herb, could reduce Clostridium coccoides and Clostridium leptum , and increase Akkermansia muciniphila in rats fed high-fat diets and could reduce production of secondary bile acids, which is important to CRC. 21 These findings provide important knowledge suggesting that different TCM herbal medicines could modulate certain gut bacteria and impact CRC development or treatment effect through immune, anti-inflammatory, or metabolic mechanisms, which is consistent with our results.…”

Section: Discussionmentioning

confidence: 99%

Quxie Capsule Modulating Gut Microbiome and Its Association With T cell Regulation in Patients With Metastatic Colorectal Cancer: Result From a Randomized Controlled Clinical Trial

et al. 2020

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Aim: Quxie capsule(QX), a TCM compound, had shown benefit on survival outcomes for metastatic colorectal cancer(mCRC) patients and could inhibit tumor growth through immune regulation. This study aimed to evaluate whether such effect is associated with gut microbiome modulation. Method: We conducted a randomized double-blinded placebo controlled clinical trial in Xiyuan Hospital, China Academy of Chinese Medical Sciences. All patients were randomly assigned into QX or placebo control group. Before and after 1-month interventions, we collected patients’ stool samples for microbiome analysis by 16s rRNA sequencing approaches, as well as blood samples to analyze T lymphocyte subsets by flow cytometry methods. Microbiome analysis among groups was done through bioinformation analysis platform. The study had been proved by the ethics committee of Xiyuan Hospital (2016XLA122-1) had been registered on Chinese Clinical Trial Registry (registration number: ChiCTR2000029599). All patients consented before enrollment. Results: We randomly assigned 40 patients and 34 were finally analyzed. Among them, 29% were female, with an average age of 63 years old, and 74% had liver or lung metastasis. Both CD4 T(TH) cell and CD8 T(TC) cell counts increased after QX treatment, while TH cells were significantly more in QX than in control group (737 vs 449, P = .024). Microbiome community analysis on Class level showed that the proportion of Actinobacteria declined in the control group, but significantly increased after QX treatments (0.83% vs 4.7%, P = .017). LEfSe analysis showed that after treatments, samples from QX group were highly related with Oscillibacter, Eubacterium, and Lachnospiraceae. RDA analysis showed that after QX interventions, stool samples and microbiome species had relevance with TC/TH cells counts but were not statistically significant. Heatmap analysis on Genus level revealed that after QX treatments, higher amounts of TH cells were significantly associated with less abundance of g_Bifidobacterium (coef. −0.76, P = .002), Collinsella (coef.−0.61, P = .02), Ruminiclostridium_9 (coef. −0.64, P = .01). Conclusion: QX capsule could enhance TH cells level among mCRC patients and increase the abundance of gut anticancer bacteria such as Actinobacteria as well as butyrate-producing bacteria such as Lachnospiraceae. These results indicated that QX capsule might have the property of dual effects of antitumor and immunity enhancement, both mediated by the microbiome.

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“…All the drugs prepared above were stored in a refrigerator at 4°C and shaken well before intragastric administration. The above drug extraction process was completed by the Pharmaceutical Research Room of Yueyang Hospital affiliated to Shanghai University of traditional Chinese Medicine ( Zhang et al, 2019 ).…”

Section: Methodsmentioning

confidence: 99%

“…To identify the components of Mume Sieb and Marci Hieronymi extract, Q Exactive high-performance benchtop quadrupole-Orbitrap LC-MS/MS was performed. The main components in the extract of CMF were identified according to the elemental composition data determined from accurate mass measurements and comparison with the literature data (this step was completed by our research group in the previous study) ( Zhang et al, 2019 ).…”

Section: Methodsmentioning

confidence: 99%

“…Traditional Chinese medicine plays an important role in the prevention and treatment of diseases. Through clustering and frequency analysis and data mining, our research group found that the core drug for the treatment of CRA was CMF, which consists of Mume Sieb 30 g and Marci Hieronymi 30 g ( Zhang et al, 2019 ). In addition, we successfully established a CRA mouse model induced by high-fat diet in combination with AOM/DSS treatment ( Guo et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Exploring the Mechanism of Action of Canmei Formula Against Colorectal Adenoma Through Multi-Omics Technique

Guo

Liu

et al. 2021

Front. Cell Dev. Biol.

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Background: Canmei formula (CMF) is a traditional Chinese medicine compound with definite effect on the prevention and treatment of colorectal adenoma (CRA). CMF can prevent the transformation of intestinal inflammation to cancer. This study explored the mechanism of action of CMF in anti-CRA using multi-omics techniques.Method: The mice were randomly divided into four groups: blank group (Control), high-fat diet (HFD) + AOM/DSS colorectal adenoma model (ADH) groups, Canmei formula treatment group (ADH-CMF) and sulfasalazine treatment group (Sul). Except for the blank group, ADH model was established in the other three groups by intraperitoneal injection with AOM reagent, and then mice were given 2.5% DSS in free drinking water and high-fat diet. The mice in the blank group and ADH groups were intragastrically perfused with normal saline, and the mice in the other two groups were treated with corresponding drugs for 20 weeks. During this period, the changes of physical signs of mice in each group were observed. The differentially expressed genes and proteins in the Control group, ADH group and ADH-CMF group were detected by RNA-seq transcriptome sequencing and Tandem Mass Tags (TMT) quantitative proteomics. After the combined analysis and verification, the key targets were analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Moreover, the changes of intestinal flora in mice of the three groups were examined.Results: A total of 2,548 differential genes were obtained by transcriptomics analysis, and 45 differential proteins were obtained by proteomics analysis. The results of proteomics data and experimental verification showed that CMF mainly affected the Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase (LHPP) target. GO analysis showed that the targets of CMF were involved in the biological processes such as cellular process, metabolic process and biological regulation. KEGG analysis showed that those genes were involved in oxidative phosphorylation, cell senescence, and metabolic pathways. Studies have shown that LHPP overexpression impeded colorectal cancer cell growth and proliferation in vitro, and was associated with a change in PI3K/AKT activity. The results of 16S DNA high-throughput sequencing showed that CMF could effectively regulate the abundance of Bifidobacterium, Candidatus_Saccharimonas and Erysipelatoclostridium in the intestinal flora at the genus level.Conclusion: CMF regulates LHPP via the PI3K/AKT signaling pathway. CMF affects the abundance of specific intestinal flora and can regulate the disorder of intestinal flora to achieve the role of prevention and treatment of CRA.

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Canmei Formula Reduces Colitis-Associated Colorectal Carcinogenesis in Mice by Modulating the Composition of Gut Microbiota

Cited by 23 publications

References 37 publications

Colorectal cancer and microbiota modulation for clinical use. A systematic review

Colorectal cancer and microbiota modulation for clinical use. A systematic review

Quxie Capsule Modulating Gut Microbiome and Its Association With T cell Regulation in Patients With Metastatic Colorectal Cancer: Result From a Randomized Controlled Clinical Trial

Exploring the Mechanism of Action of Canmei Formula Against Colorectal Adenoma Through Multi-Omics Technique

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