Association of Flavonifractor plautii, a Flavonoid-Degrading Bacterium, with the Gut Microbiome of Colorectal Cancer Patients in India

ABSTRACT Recently, dysbiosis in the human gut microbiome and shifts in the relative abundances of several bacterial species have been recognized as important factors in colorectal cancer (CRC). However, these studies have been carried out mainly in developed countries where CRC has a high incidence, and it is unclear whether the host-microbiome relationships deduced from these studies can be generalized to the global population. To test if the documented associations between the microbiome and CRC are conserved in a distinct context, we performed metagenomic and metabolomic association studies on fecal samples from 30 CRC patients and 30 healthy controls from two different locations in India, followed by a comparison of CRC data available from other populations. We confirmed the association of Bacteroides and other bacterial taxa with CRC that have been previously reported in other studies. However, the association of CRC with Flavonifractor plautii in Indian patients emerged as a novel finding. The plausible role of F. plautii appears to be linked with the degradation of beneficial anticarcinogenic flavonoids, which was also found to be significantly correlated with the enzymes and modules involved in flavonoid degradation within Indian CRC samples. Thus, we hypothesize that the degradation of beneficial flavonoids might be playing a role in cancer progression within this Indian cohort. We also identified 20 potential microbial taxonomic markers and 33 potential microbial gene markers that discriminate the Indian CRC from healthy microbiomes with high accuracy based on machine learning approaches. IMPORTANCE This study provides novel insights on the CRC-associated microbiome of a unique cohort in India, reveals the potential role of a new bacterium in CRC, and identifies cohort-specific biomarkers, which can potentially be used in noninvasive diagnosis of CRC. The study gains additional significance, as India is among the countries with a very low incidence of CRC, and the diet and lifestyle in India have been associated with a distinct gut microbiome in healthy Indians compared to other global populations. Thus, in this study, we hypothesize a unique relationship between CRC and the gut microbiome in an Indian population.

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Metagenome-wide association study of gut microbiome features for myositis

10.1101/2021.12.15.21267821 ◽

2021 ◽

Author(s):

Yimin Li ◽

Jun Xu ◽

Zijun Li ◽

Yixue Guo ◽

Xiaoyan Xing ◽

...

Keyword(s):

Escherichia Coli ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Gut Microbiome ◽

Association Studies ◽

Bacterial Species ◽

Biological Pathways ◽

Healthy Controls ◽

E Coli

Objective: The clinical relevance and pathogenic role of gut microbiome in both myositis and its associated interstitial lung disease (ILD) are still unclear. The purpose of this study was to investigate the role of gut microbiome in myositis through comprehensive metagenomic-wide association studies (MWAS). Methods We conducted MWAS of the myositis gut microbiome in a Chinese cohort by using whole-genome shotgun sequencing of high depth, including 30 myositis patients and 31 healthy controls (HC). Among the myositis patients, 11 developed rapidly progressive interstitial lung disease (RP-ILD) and 10 had chronic ILD (C-ILD). Our MWAS consisted of both overall distribution level of the bacteria analysis and pathway analysis. Receiver operating characteristic curve (ROC) analysis was performed to identify novel gut bacterial species associated with myositis or myositis-associated RP-ILD, and to evaluate their diagnostic values. Results Apparent discrepancy in β diversities of metagenome was found in the comparison of myositis and HC, RP-ILD and C-ILD in myositis. Analysis for overall distribution level of the bacteria showed Alistipes onderdonkii, Parabacteroides distasonis and Escherichia coli were upregulated, Lachnospiraceae bacterium GAM79, Roseburia intestinalis, and Akkermansia muciniphila were downregulated in patients with myositis compared to HC. Bacteroides thetaiotaomicron, Parabacteroides distasonis and Escherichia coli were upregulated, Bacteroides A1C1 and Bacteroides xylanisolvens were downregulated in RP-ILD cases compared with C-ILD cases. A variety of biological pathways related to metabolism were enriched in the myositis and HC, RP-ILD and C-ILD comparison. And in the analyses for microbial contribution in metagenomic biological pathways, we have found that E. coli played an important role in the pathway expression in both myositis group and myositis-associated RP-ILD group. Anti-PL-12 antibody, anti-Ro-52 antibody, and anti-EJ antibody were found to have positive correlation with bacterial diversity (Shannon-wiener diversity index and Chao1, richness estimator) between myositis group and control groups. The combination of E. coli and R. intestinalis could distinguish myositis group from Healthy controls effectively. R. intestinalis can also be applied in the distinguishment of RP-ILD group vs. C-ILD group in myositis paitents. Conclusion Our MWAS study first revealed the link between gut microbiome and pathgenesis of myositis, which may help us understand the role of gut microbiome in the etiology of myositis and myositis-associated RP-ILD.

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Potential Role of the Gut Microbiome In Colorectal Cancer Progression

Frontiers in Immunology ◽

10.3389/fimmu.2021.807648 ◽

2022 ◽

Vol 12 ◽

Author(s):

Jaeho Kim ◽

Heung Kyu Lee

Keyword(s):

Colorectal Cancer ◽

Gut Microbiota ◽

Cancer Treatment ◽

Cancer Progression ◽

Gut Microbiome ◽

Intestinal Inflammation ◽

Treatment Modalities ◽

Host Immune System ◽

Anti Cancer

An increasing number of studies have revealed that the progression of colorectal cancer (CRC) is related to gut microbiome composition. Under normal conditions, the gut microbiome acts as a barrier to other pathogens or infections in the intestine and modulates inflammation by affecting the host immune system. These gut microbiota are not only related to the intestinal inflammation associated with tumorigenesis but also modulation of the anti-cancer immune response. Thus, they are associated with tumor progression and anti-cancer treatment efficacy. Studies have shown that the gut microbiota can be used as biomarkers to predict the effect of immunotherapy and improve the efficacy of immunotherapy in treating CRC through modulation. In this review, we discuss the role of the gut microbiome as revealed by recent studies of the growth and progression of CRC along with its synergistic effect with anti-cancer treatment modalities.

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Guild-based analysis for understanding gut microbiome in human health and diseases

Genome Medicine ◽

10.1186/s13073-021-00840-y ◽

2021 ◽

Vol 13 (1) ◽

Cited By ~ 2

Author(s):

Guojun Wu ◽

Naisi Zhao ◽

Chenhong Zhang ◽

Yan Y. Lam ◽

Liping Zhao

Keyword(s):

Gut Microbiota ◽

Human Health ◽

Gut Microbiome ◽

Association Studies ◽

Causative Role ◽

Disease Phenotypes ◽

Genetic Complexity ◽

Causative Agents ◽

Specific Health

AbstractTo demonstrate the causative role of gut microbiome in human health and diseases, we first need to identify, via next-generation sequencing, potentially important functional members associated with specific health outcomes and disease phenotypes. However, due to the strain-level genetic complexity of the gut microbiota, microbiome datasets are highly dimensional and highly sparse in nature, making it challenging to identify putative causative agents of a particular disease phenotype. Members of an ecosystem seldomly live independently from each other. Instead, they develop local interactions and form inter-member organizations to influence the ecosystem’s higher-level patterns and functions. In the ecological study of macro-organisms, members are defined as belonging to the same “guild” if they exploit the same class of resources in a similar way or work together as a coherent functional group. Translating the concept of “guild” to the study of gut microbiota, we redefine guild as a group of bacteria that show consistent co-abundant behavior and likely to work together to contribute to the same ecological function. In this opinion article, we discuss how to use guilds as the aggregation unit to reduce dimensionality and sparsity in microbiome-wide association studies for identifying candidate gut bacteria that may causatively contribute to human health and diseases.

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Role of lung and gut microbiota on lung cancer pathogenesis

Journal of Cancer Research and Clinical Oncology ◽

10.1007/s00432-021-03644-0 ◽

2021 ◽

Author(s):

Yue Zhao ◽

Yuxia Liu ◽

Shuang Li ◽

Zhaoyun Peng ◽

Xiantao Liu ◽

...

Keyword(s):

Lung Cancer ◽

Gut Microbiota ◽

Cancer Progression ◽

Gut Microbiome ◽

Intestinal Flora ◽

Inflammatory Factors ◽

Cancer Pathogenesis ◽

Research Findings ◽

Relationship Of

Abstract Background Lung cancer is the leading cause of cancer-related deaths worldwide (Ferlay et al., Int J Cancer 136:E359–386, 2015). In addition, lung cancer is associated with the highest mortality among all cancer types (Wu et al., Exp Ther Med 16:3004–3010, 2018). Previous studies report that microbiota play an important role in lung cancer. Notably, changes in lung and gut microbiota, are associated with progression of lung cancer. Several studies report that lung and gut microbiome promote lung cancer initiation and development by modulating metabolic pathways, inhibiting the function of immune cells, and producing pro-inflammatory factors. In addition, some factors such as microbiota dysbiosis, affect production of bacteriotoxins, genotoxicity and virulence effect, therefore, they play a key role in cancer progression. These findings imply that lung and gut microbiome are potential markers and targets for lung cancer. However, the role of microbiota in development and progression of lung cancer has not been fully explored. Purpose The aim of this study was to systemically review recent research findings on relationship of lung and gut microbiota with lung cancer. In addition, we explored gut–lung axis and potential mechanisms of lung and gut microbiota in modulating lung cancer progression. Conclusion Pulmonary and intestinal flora influence the occurrence, development, treatment and prognosis of lung cancer, and will provide novel strategies for prevention, diagnosis, and treatment of lung cancer.

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A Metabolic Model of Intestinal Secretions: The Link between Human Microbiota and Colorectal Cancer Progression

Metabolites ◽

10.3390/metabo11070456 ◽

2021 ◽

Vol 11 (7) ◽

pp. 456

Author(s):

Pejman Salahshouri ◽

Modjtaba Emadi-Baygi ◽

Mahdi Jalili ◽

Faiz M. Khan ◽

Olaf Wolkenhauer ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Gut Microbiome ◽

Metabolic Model ◽

System Level ◽

Mathematical Framework ◽

Bacterial Populations ◽

Colorectal Cancer Progression ◽

Genome Scale ◽

High Throughput Data Analysis

The human gut microbiota plays a dual key role in maintaining human health or inducing disorders, for example, obesity, type 2 diabetes, and cancers such as colorectal cancer (CRC). High-throughput data analysis, such as metagenomics and metabolomics, have shown the diverse effects of alterations in dynamic bacterial populations on the initiation and progression of colorectal cancer. However, it is well established that microbiome and human cells constantly influence each other, so it is not appropriate to study them independently. Genome-scale metabolic modeling is a well-established mathematical framework that describes the dynamic behavior of these two axes at the system level. In this study, we created community microbiome models of three conditions during colorectal cancer progression, including carcinoma, adenoma and health status, and showed how changes in the microbial population influence intestinal secretions. Conclusively, our findings showed that alterations in the gut microbiome might provoke mutations and transform adenomas into carcinomas. These alterations include the secretion of mutagenic metabolites such as H2S, NO compounds, spermidine and TMA, as well as the reduction of butyrate. Furthermore, we found that the colorectal cancer microbiome can promote inflammation, cancer progression (e.g., angiogenesis) and cancer prevention (e.g., apoptosis) by increasing and decreasing certain metabolites such as histamine, glutamine and pyruvate. Thus, modulating the gut microbiome could be a promising strategy for the prevention and treatment of CRC.

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Cooperation of SRPK2, Numb and p53 in the malignant biology and chemosensitivity of colorectal cancer

Bioscience Reports ◽

10.1042/bsr20191488 ◽

2020 ◽

Vol 40 (1) ◽

Author(s):

Guosen Wang ◽

Weiwei Sheng ◽

Jingtong Tang ◽

Xin Li ◽

Jianping Zhou ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Migration ◽

Cancer Progression ◽

Molecular Mechanisms ◽

Migration And Invasion ◽

Chemical Agent ◽

Cell Migration And Invasion ◽

Agent Treatment ◽

Hct116 Cells

Abstract Serine-arginine protein kinase 2 (SRPK2) is aberrantly expressed in human malignancies including colorectal cancer (CRC). However, little is known about the molecular mechanisms, and the role of SRPK2 in chemosensitivity remains unexplored in CRC. We recently showed that SRPK2 promotes pancreatic cancer progression by down-regulating Numb and p53. Therefore, we investigated the cooperation between SRPK2, Numb and p53 in the cell migration, invasion and chemosensitivity of CRC in vitro. Here, we showed that SRPK2 expression was higher in CRC tumors than in nontumor tissues. SRPK2 expression was positively associated with clinicopathological characteristics of CRC patients, including tumor differentiation, T stage, N stage and UICC stage. Additionally, SRPK2 had no association with mutant p53 (mtp53) in SW480 and SW620 cells, but negatively regulated Numb and wild-type p53 (wtp53) in response to 5-fluorouracil or cisplatin treatment in HCT116 cells. Moreover, SRPK2, Numb and p53 coimmunoprecipitated into a triple complex with or without the treatment of 5-fluorouracil in HCT116 cells, and p53 knockdown reversed the up-regulation of wtp53 induced by SRPK2 silencing with chemical agent treatment. Furthermore, overexpression of SRPK2 increased cell migration and invasion and decreased chemosensitivity to 5-fluorouracil or cisplatin in HCT116 cells. Conversely, SRPK2 silencing decreased cell migration and invasion and increased chemosensitivity to 5-fluorouracil or cisplatin, yet these effects could be reversed by p53 knockdown under chemical agent treatment. These results thus reveal a novel role of SRPK2-Numb-p53 signaling in the progression of CRC and demonstrate that SRPK2 is a potential therapeutic target for CRC clinical therapy.

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Role of the IL-33/ST2L axis in colorectal cancer progression

Cellular Immunology ◽

10.1016/j.cellimm.2017.12.014 ◽

2019 ◽

Vol 343 ◽

pp. 103740 ◽

Cited By ~ 4

Author(s):

Miho Akimoto ◽

Keizo Takenaga

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Colorectal Cancer Progression

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Role of Herbal Medicine/Phyto-Therapy in Cancer Prevention by Inhibiting Epithelial-Mesenchymal Transition (EMT) Pathways

Treating Endocrine and Metabolic Disorders With Herbal Medicines - Advances in Medical Diagnosis, Treatment, and Care ◽

10.4018/978-1-7998-4808-0.ch009 ◽

2021 ◽

pp. 215-234

Author(s):

Rekha Gahtori ◽

Ashutosh Paliwal

Keyword(s):

Cancer Progression ◽

Epithelial Mesenchymal Transition ◽

Raw Materials ◽

Human Life ◽

Developed Countries ◽

Mesenchymal Transition ◽

Synthetic Drugs ◽

Extracellular Signals ◽

Different Levels

Human life is surrounded and dependent on its environment. Human civilization is nurtured by nature as it provides raw materials that are used in the manufacturing of various essential products like medicine, food items, etc. Not only developing countries but developed countries also depend on herbal-based medications. Cancer is a global health burden. Epithelial-mesenchymal-transition (EMT) plays a key role in cancer progression and is also stimulated by different extracellular signals and could be regulated at different levels. Conventional therapies exhibit a cytotoxic effect, which encourages the development of a new approach that could be used with synthetic drugs. Phytotherapy emerged as an effective weapon against cancer. Herbal drugs directly target different signaling pathways that promote EMT and eventually lead to cancer.

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