scholarly journals The Comparison of Fecal Microbiota in Left-Side and Right-Side Human Colorectal Cancer

2021 ◽  
pp. 1-7
Author(s):  
Toru Miyake ◽  
Haruki Mori ◽  
Daiki Yasukawa ◽  
Zhang Hexun ◽  
Hiromitsu Maehira ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Clinical Status ◽  
Intestinal Flora ◽  
Tumor Location ◽  
Fecal Microbiota ◽  
Vital Role ◽  
Human Colorectal Cancer ◽  
Linear Discriminant ◽  
Biological Differences

<b><i>Introduction:</i></b> Microbiomes play a vital role in the development and progression of cancer. The clinical status, including prognosis, genetic mutations, and sensitivity to chemotherapy, differs depending on the location of colorectal cancer (CRC); however, the association between gut microbiota and the location of CRC is not entirely understood. This study was conducted to evaluate the differences in the gut microbiota in patients with CRC according to the location of the tumor. <b><i>Methods:</i></b> Fifty-six patients who underwent surgery for CRC between August 2018 and November 2019 were included in the study. Three patients who had received neoadjuvant therapy or antibiotic treatment within 1 month before surgery were excluded. The metagenomes of microbiota in preoperative feces were assessed using the V3–V4 region of 16s rRNA amplicon sequences. <b><i>Results:</i></b> The beta diversity of the Bray-Curtis distance was significantly higher in left-sided than in right-sided CRC. <i>Fusobacterium</i> predominated in left-sided CRC according to the linear discriminant analysis effect size method. <i>Blautia</i>, Eryspelotrichales, <i>Holdemanella</i>, <i>Faecalibacterium</i>, <i>Subdoligranulum</i>, and <i>Dorea</i> constituted the dominant intestinal flora in right-sided CRC. Pathway analysis revealed that L-lysine fermentation and cob(II)yrinate a,c-diamide biosynthesis I were predominant in left-sided CRC. <b><i>Discussion:</i></b> This study demonstrated that fecal microbiota in left-sided CRC constitutionally and functionally differ from those in right-side CRC. These results will help to elucidate the biological differences according to tumor location and develop treatments for human CRC.

scholarly journals Gut Microbiota-Derived Metabolites in Colorectal Cancer: The Bad and the Challenges

2021 ◽  
Vol 11 ◽  
Author(s):  
Wanru Zhang ◽  
Yaping An ◽  
Xiali Qin ◽  
Xuemei Wu ◽  
Xinyu Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Current Knowledge ◽  
Fecal Microbiota ◽  
Vital Role ◽  
Nitroso Compounds ◽  
Great Promise ◽  
Complex Ecosystem ◽  
Crc Management

Accumulating evidence from studies in humans and animal models has elucidated that gut microbiota, acting as a complex ecosystem, contributes critically to colorectal cancer (CRC). The potential mechanisms often reported emphasize the vital role of carcinogenic activities of specific pathogens, but in fact, a series of metabolites produced from exogenous dietary substrates or endogenous host compounds occupy a decisive position similarly. Detrimental gut microbiota-derived metabolites such as trimethylamine-N-oxide, secondary bile acids, hydrogen sulfide and N-nitroso compounds could reconstruct the ecological composition and metabolic activity of intestinal microorganisms and formulate a microenvironment that opens susceptibility to carcinogenic stimuli. They are implicated in the occurrence, progression and metastasis of CRC through different mechanisms, including inducing inflammation and DNA damage, activating tumorigenic signaling pathways and regulating tumor immunity. In this review, we mainly summarized the intimate relationship between detrimental gut microbiota-derived metabolites and CRC, and updated the current knowledge about detrimental metabolites in CRC pathogenesis. Then, multiple interventions targeting these metabolites for CRC management were critically reviewed, including diet modulation, probiotics/prebiotics, fecal microbiota transplantation, as well as more precise measures such as engineered bacteria, phage therapy and chemopreventive drugs. A better understanding of the interplay between detrimental microbial metabolites and CRC would hold great promise against CRC.

scholarly journals Interplay between the Gut Microbiota and Inflammatory Mediators in the Development of Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 734
Author(s):  
Gwangbeom Heo ◽  
Yunna Lee ◽  
Eunok Im
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Inflammatory Mediators ◽  
Tumor Metastasis ◽  
Intestinal Tract ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Therapeutic Interventions ◽  
Potential Therapeutic Target ◽  
Necrosis Factor

Inflammatory mediators modulate inflammatory pathways during the development of colorectal cancer. Inflammatory mediators secreted by both immune and tumor cells can influence carcinogenesis, progression, and tumor metastasis. The gut microbiota, which colonize the entire intestinal tract, especially the colon, are closely linked to colorectal cancer through an association with inflammatory mediators such as tumor necrosis factor, nuclear factor kappa B, interleukins, and interferons. This association may be a potential therapeutic target, since therapeutic interventions targeting the gut microbiota have been actively investigated in both the laboratory and in clinics and include fecal microbiota transplantation and probiotics.

scholarly journals A Crosstalk between Diet, Microbiome and microRNA in Epigenetic Regulation of Colorectal Cancer

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2428
Author(s):  
Małgorzata Guz ◽  
Witold Jeleniewicz ◽  
Anna Malm ◽  
Izabela Korona-Glowniak
Keyword(s):  
Colorectal Cancer ◽  
Gastrointestinal Tract ◽  
Gut Microbiota ◽  
Intestinal Microbiota ◽  
Current Knowledge ◽  
Vital Role ◽  
Disease States ◽  
Health And Disease ◽  
Dietary Components ◽  
Non Coding Rnas

A still growing interest between human nutrition in relation to health and disease states can be observed. Dietary components shape the composition of microbiota colonizing our gastrointestinal tract which play a vital role in maintaining human health. There is a strong evidence that diet, gut microbiota and their metabolites significantly influence our epigenome, particularly through the modulation of microRNAs. These group of small non-coding RNAs maintain cellular homeostasis, however any changes leading to impaired expression of miRNAs contribute to the development of different pathologies, including neoplastic diseases. Imbalance of intestinal microbiota due to diet is primary associated with the development of colorectal cancer as well as other types of cancers. In the present work we summarize current knowledge with particular emphasis on diet-microbiota-miRNAs axis and its relation to the development of colorectal cancer.

scholarly journals Study of the Relationship between Microbiome and Colorectal Cancer Susceptibility Using 16SrRNA Sequencing

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Wanxin Liu ◽  
Ren Zhang ◽  
Rong Shu ◽  
Jinjing Yu ◽  
Huan Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Cancer Susceptibility ◽  
Precancerous Lesions ◽  
Bacterial Community Composition ◽  
Intestinal Flora ◽  
Control Group ◽  
Healthy Controls ◽  
Healthy Individuals

A lot of previous studies have recently reported that the gut microbiota influences the development of colorectal cancer (CRC) in Western countries, but the role of the gut microbiota in Chinese population must be investigated fully. The goal of this study was to determine the role of the gut microbiome in the initiation and development of CRC. We collected fecal samples of 206 Chinese individuals: 59 with polyp (group P), 54 with adenoma (group A), 51 with colorectal cancer (group CC), and 42 healthy controls (group HC).16S ribosomal RNA (rRNA) was used to compare the microbiota community structures among healthy controls, patients with polyp, and those with adenoma or colorectal cancer. Our study proved that intestinal flora, as a specific indicator, showed significant differences in its diversity and composition. Sobs, Chao, and Ace indexes of group CC were significantly lower than those of the healthy control group (CC group: Sobs, Chao, and Ace indexes were 217.3 ± 69, 4265.1 ± 80.7, and 268.6 ± 78.1, respectively; HC group: Sobs, Chao, and Ace indexes were 228.8 ± 44.4, 272.9 ± 58.6, and 271.9 ± 57.2, respectively). When compared with the healthy individuals, the species richness and diversity of intestinal flora in patients with colorectal cancer were significantly reduced: PCA and PCoA both revealed that a significant separation in bacterial community composition between the CC group and HC group (with PCA using the first two principal component scores of PC1 14.73% and PC2 10.34% of the explained variance, respectively; PCoA : PC1 = 14%, PC2 = 9%, PC3 = 6%). Wilcox tests was used to analyze differences between the two groups, it reveals that Firmicutes (P=0.000356), Fusobacteria (P=0.000001), Proteobacteria (P=0.000796), Spirochaetes (P=0.013421), Synergistetes (P=0.005642) were phyla with significantly different distributions between cases and controls. The proportion of microorganism composition is varying at different stages of colon cancer development: Bacteroidetes (52.14%) and Firmicutes (35.88%) were enriched in the healthy individuals; on the phylum level, the abundance of Bacteroidetes (52.14%-53.92%-52.46%–47.06%) and Firmicutes (35.88%-29.73%-24.27%–25.36%) is decreasing with the development of health-polyp-adenomas-CRC, and the abundance of Proteobacteria (9.33%-12.31%-16.51%–22.37%) is increasing. PCA and PCOA analysis showed there was no significant (P<0.05) difference in species similarity between precancerous and carcinogenic states. However, the composition of the microflora in patients with precancerous lesions (including patients with adenoma and polyp) was proved to have no significant disparity (P<0.05). Our study provides insights into new angles to dig out potential biomarkers in diagnosis and treatment of colorectal cancer and to provide scientific advice for a healthy lifestyle for the sake of gut microbiota.

scholarly journals LncRNA HOTAIR is a Prognostic Biomarker for the Proliferation and Chemoresistance of Colorectal Cancer via MiR-203a-3p-Mediated Wnt/ß-Catenin Signaling Pathway

2018 ◽  
Vol 46 (3) ◽  
pp. 1275-1285 ◽  
Author(s):  
Zhigang Xiao ◽  
Zhan Qu ◽  
Zhikang Chen ◽  
Zhixue Fang ◽  
Ke Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Antisense Rna ◽  
Vital Role ◽  
Loss Of Function ◽  
Human Colorectal Cancer ◽  
Expression Levels ◽  
Lncrna Hotair

Background/Aims: HOX transcript antisense RNA (HOTAIR) plays a vital role in carcinogenesis. However, its functional and regulatory roles remain unclear. In this study, we aimed to investigate its biological function and clinical significance in human colorectal cancer (CRC). Methods: We examined the expression levels of lncRNA HOTAIR and miR-203a-3p in CRC tissues and CRC cell lines by qRT-PCR. Gain and loss-of-function assays were performed to examine the effects of HOTAIR and miR-203a-3p on the proliferation and chemoresistance of CRC cells. The possible mechanisms of HOTAIR were also explored by fluorescence reporter assay and Western blot. Results: The expressions of HOTAIR were upregulated in CRC tissue tissues compared to adjacent control tissues. We also found HOTAIR was downregulated by miR-203a-3p in CRC cell lines. Both HOTAIR knockdown and miR-203a-3p overexpression in CRC cell lines led to inhibited cell proliferation and reduced chemoresistance. We also determined that β-catenin and GRG5 were inhibitory targets of miR-203a-3p, and that Wnt/β-catenin signaling was inhibited by both HOTAIR knockdown and miR-203a-3p overexpression. Significantly, we found that increased expression of miR-203a-3p is essential for cell proliferation repression, chemoresistance reduction, and Wnt/β-catenin signaling inhibition induced by HOTAIR knockdown. Conclusions: Our study demonstrated that the lncRNA HOTAIR could regulate the progression and chemoresistance of CRC via modulating the expression levels of miR-203a-3p and the activity of Wnt/β-catenin signaling pathway.

scholarly journals Effect of Fiber and Fecal Microbiota Transplantation Donor on Recipient Mice Gut Microbiota

2021 ◽  
Vol 12 ◽  
Author(s):  
Yifan Zhong ◽  
Jiahong Cao ◽  
Zhaoxi Deng ◽  
Yanfei Ma ◽  
Jianxin Liu ◽  
...  
Keyword(s):  
Random Forest ◽  
Gut Microbiota ◽  
Dietary Fiber ◽  
Fecal Microbiota Transplantation ◽  
Critical Role ◽  
Fecal Microbiota ◽  
Linear Discriminant ◽  
High Fiber ◽  
Significant Difference ◽  
Random Forest Models

Both fecal microbiota transplantation (FMT) and dietary fiber intervention were verified as effective ways to manipulate the gut microbiota, whereas little is known about the influence of the combined methods on gut microbiota. Here, we constructed “non-industrialized” and “industrialized” gut microbiota models to investigate the donor effect of FMT and diet effect in shaping the gut microbiota. Mice were transplanted fecal microbiota from domestic pig and received a diet with low-fiber (D) or high-fiber (DF), whereas the other two groups were transplanted fecal microbiota from wild pig and then received a diet with low-fiber (W) or high-fiber (WF), respectively. Gut microbiota of WF mice showed a lower Shannon and Simpson index (P &lt; 0.05), whereas gut microbiota of W mice showed no significant difference than that of D and DF mice. Random forest models revealed the major differential bacteria genera between four groups, including Anaeroplasma or unclassified_o_Desulfovibrionales, which were influenced by FMT or diet intervention, respectively. Besides, we found a lower out-of-bag rate in the random forest model constructed for dietary fiber (0.086) than that for FMT (0.114). Linear discriminant analysis effective size demonstrated that FMT combined with dietary fiber altered specific gut microbiota, including Alistipes, Clostridium XIVa, Clostridium XI, and Akkermansia, in D, DF, W, and WF mice, respectively. Our results revealed that FMT from different donors coupled with dietary fiber intervention could lead to different patterns of gut microbiota composition, and dietary fiber might play a more critical role in shaping gut microbiota than FMT donor. Strategies based on dietary fiber can influence the effectiveness of FMT in the recipient.

scholarly journals Abstract 952: Modulation of immune cell trafficking into human colorectal cancer by gut microbiota

2017 ◽  
Author(s):  
Eleonora Cremonesi ◽  
Jesus G. Garzón ◽  
Valeria Governa ◽  
Valentina Mele ◽  
Francesca Amicarella ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Immune Cell ◽  
Cell Trafficking ◽  
Human Colorectal Cancer ◽  
Immune Cell Trafficking

scholarly journals The Fecal Microbiota of Dogs Switching to a Raw Diet Only Partially Converges to That of Wolves

2021 ◽  
Vol 12 ◽  
Author(s):  
Jia Xu ◽  
Anne A. M. J. Becker ◽  
Yu Luo ◽  
Wenfu Zhang ◽  
Bingqian Ge ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota ◽  
Linear Discriminant ◽  
Raw Meat ◽  
Dietary Shift ◽  
Microbial Profile ◽  
Meat Diet ◽  
Fermenting Bacteria ◽  
Microbial Groups ◽  
Diet Shifts

The genomic signature of dog domestication reveals adaptation to a starch-rich diet compared with their ancestor wolves. Diet is a key element to shape gut microbial populations in a direct way as well as through coevolution with the host. We investigated the dynamics in the gut microbiota of dogs when shifting from a starch-rich, processed kibble diet to a nature-like raw meat diet, using wolves as a wild reference. Six healthy wolves from a local zoo and six healthy American Staffordshire Terriers were included. Dogs were fed the same commercial kibble diet for at least 3 months before sampling at day 0 (DC), and then switched to a raw meat diet (the same diet as the wolves) for 28 days. Samples from the dogs were collected at day 1 (DR1), week 1 (DR7), 2 (DR14), 3 (DR21), and 4 (DR28). The data showed that the microbial population of dogs switched from kibble diet to raw diet shifts the gut microbiota closer to that of wolves, yet still showing distinct differences. At phylum level, raw meat consumption increased the relative abundance of Fusobacteria and Bacteroidetes at DR1, DR7, DR14, and DR21 (q &lt; 0.05) compared with DC, whereas no differences in these two phyla were observed between DC and DR28. At genus level, Faecalibacterium, Catenibacterium, Allisonella, and Megamonas were significantly lower in dogs consuming the raw diet from the first week onward and in wolves compared with dogs on the kibble diet. Linear discriminant analysis effect size (LEfSe) showed a higher abundance of Stenotrophomonas, Faecalibacterium, Megamonas, and Lactobacillus in dogs fed kibble diet compared with dogs fed raw diet for 28 days and wolves. In addition, wolves had greater unidentified Lachnospiraceae compared with dogs irrespective of the diets. These results suggested that carbohydrate-fermenting bacteria give way to protein fermenters when the diet is shifted from kibble to raw diet. In conclusion, some microbial phyla, families, and genera in dogs showed only temporary change upon dietary shift, whereas some microbial groups moved toward the microbial profile of wolves. These findings open the discussion on the extent of coevolution of the core microbiota of dogs throughout domestication.

Dysbiosis of Fecal Microbiota in Allergic Rhinitis Patients

2020 ◽  
Vol 34 (5) ◽  
pp. 650-660 ◽  
Author(s):  
Xiang Liu ◽  
Jing Tao ◽  
Jing Li ◽  
Xiaolin Cao ◽  
Yong Li ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Statistical Analysis ◽  
Gut Microbiota ◽  
Study Groups ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Linear Discriminant ◽  
Α Diversity ◽  
Gut Microbiota Composition

Background The gut microbiota plays an important role in shaping the immune system and may be closely connected to the development of allergic diseases. Objective This study aimed to determine the gut microbiota composition in Chinese allergic rhinitis (AR) patients as compared with healthy controls (HCs). Methods We collected stool samples from 93 AR patients and 72 age- and sex-matched HCs. Gut microbiota composition was analyzed using QIIME targeting the 16S rRNA gene. Functional pathways were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. Statistical analysis was performed using the R program, linear discriminant analysis effect size (LefSe), analysis of QIIME, and statistical analysis of metagenomic profiles, among other tests. Results Compared with HCs, AR patients had significantly lower gut-microbiota α-diversity ( P < .001). The gut microbiota composition significantly differed between the 2 study groups. At the phylum level, the relative abundance of Bacteroidetes was higher while those of Actinobacteria and Proteobacteria were lower in the AR group than in the HC group ( P < .001, q < 0.001). At the genus level, Escherichia-Shigella, Prevotella, and Parabacteroides ( P < .001, q < 0.001) had significantly higher relative abundances in the AR group than in the HC group. LefSe analysis indicated that Escherichia-Shigella, Lachnoclostridium, Parabacteroides, and Dialister were potential biomarkers for AR. In addition, predictive metagenome functional analysis showed that pyruvate, porphyrin, chlorophyll, purine metabolism, and peptidoglycan biosynthesis significantly differed between the AR and HC groups. Conclusion A comparison of the gut microbiota of AR patients and HCs suggested that dysbiosis of the fecal microbiota is involved in the development of AR. The present results may reveal key differences and identify targets for preventive or therapeutic intervention.

scholarly journals Gut microbiota modulate T cell trafficking into human colorectal cancer

Gut ◽  
2018 ◽  
Vol 67 (11) ◽  
pp. 1984-1994 ◽  
Author(s):  
Eleonora Cremonesi ◽  
Valeria Governa ◽  
Jesus Francisco Glaus Garzon ◽  
Valentina Mele ◽  
Francesca Amicarella ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
T Cell ◽  
Gut Microbiota ◽  
Cell Trafficking ◽  
Human Colorectal Cancer ◽  
Chemokine Production ◽  
T Cell Trafficking

ObjectiveTumour-infiltrating lymphocytes (TILs) favour survival in human colorectal cancer (CRC). Chemotactic factors underlying their recruitment remain undefined. We investigated chemokines attracting T cells into human CRCs, their cellular sources and microenvironmental triggers.DesignExpression of genes encoding immune cell markers, chemokines and bacterial 16S ribosomal RNA (16SrRNA) was assessed by quantitative reverse transcription-PCR in fresh CRC samples and corresponding tumour-free tissues. Chemokine receptor expression on TILs was evaluated by flow cytometry on cell suspensions from digested tissues. Chemokine production by CRC cells was evaluated in vitro and in vivo, on generation of intraperitoneal or intracecal tumour xenografts in immune-deficient mice. T cell trafficking was assessed on adoptive transfer of human TILs into tumour-bearing mice. Gut flora composition was analysed by 16SrRNA sequencing.ResultsCRC infiltration by distinct T cell subsets was associated with defined chemokine gene signatures, including CCL5, CXCL9 and CXCL10 for cytotoxic T lymphocytes and T-helper (Th)1 cells; CCL17, CCL22 and CXCL12 for Th1 and regulatory T cells; CXCL13 for follicular Th cells; and CCL20 and CCL17 for interleukin (IL)-17-producing Th cells. These chemokines were expressed by tumour cells on exposure to gut bacteria in vitro and in vivo. Their expression was significantly higher in intracecal than in intraperitoneal xenografts and was dramatically reduced by antibiotic treatment of tumour-bearing mice. In clinical samples, abundance of defined bacteria correlated with high chemokine expression, enhanced T cell infiltration and improved survival.ConclusionsGut microbiota stimulate chemokine production by CRC cells, thus favouring recruitment of beneficial T cells into tumour tissues.

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