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 HUMAN GUT MICROBIOTA AND ITS EFFECTS ON HUMAN HEALTH IN NORMAL AND PATHOLOGICAL CONDITIONS

2017 ◽  
Vol 64 (3) ◽  
pp. 185-193
Author(s):  
Anca Magdalena Munteanu ◽  
◽  
Raluca Cursaru ◽  
Loreta Guja ◽  
Simona Carniciu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
New Technologies ◽  
Fecal Microbiota Transplantation ◽  
Current Knowledge ◽  
Gastrointestinal Diseases ◽  
Fecal Microbiota ◽  
Research Subjects ◽  
Human Gut ◽  
Human Host ◽  
Human Gut Microbiota

The medical research of the last 1-2 decades allows us to look at the human gut microbiota and microbiome as to a structure that can promote health and sometimes initiate disease. It works like an endocrine organ: releasing specific metabolites, using environmental inputs, e.g. diet, or acting through its structural compounds, that signal human host receptors, to finally contributing to the pathogenesis of several gastrointestinal and non-gastrointestinal diseases. The same commensal microbes were found as shapers of the human host response to drugs (cardiovascular, oncology etc.). New technologies played an important role in these achievements, facilitating analysis of the genetic and metabolic profile of this microbial community. Once the inputs, the pathways and a lot of human host receptors were highlighted, the scientists were encouraged to go further into research, in order to develop new pathogenic therapies, targeting the human gut flora. Dual therapies, evolving these “friend microbes”, are another actual research subjects. This review gives an update on the current knowledge in the area of microbiota disbalances under environmental factors, the contribution of gut microbiota and microbiome to the pathogenesis of obesity, obesity associated metabolic disorders and cardiovascular disease, as well as new perspectives in preventing and treating these diseases, with high prevalence in contemporary, economically developed societies. It brings the latest and most relevant evidences relating to: probiotics, prebiotics, polyphenols and fecal microbiota transplantation, dietary nutrient manipulation, microbial as well as human host enzyme manipulation, shaping human responses to currently used drugs, manipulating the gut microbiome by horizontal gene transfer.

scholarly journals Gut Microbiota Manipulation as a Tool for Colorectal Cancer Management: Recent Advances in Its Use for Therapeutic Purposes

2020 ◽  
Vol 21 (15) ◽  
pp. 5389
Author(s):  
Federica Perillo ◽  
Chiara Amoroso ◽  
Francesco Strati ◽  
Maria Rita Giuffrè ◽  
Angélica Díaz-Basabe ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Targeted Therapies ◽  
Inflammatory Responses ◽  
Fecal Microbiota Transplantation ◽  
Large Body ◽  
Cancer Recurrence ◽  
Fecal Microbiota ◽  
Cancer Management ◽  
Host Microbe Interactions

Colorectal cancer (CRC) is a multifaceted disease influenced by both environmental and genetic factors. A large body of literature has demonstrated the role of gut microbes in promoting inflammatory responses, creating a suitable microenvironment for the development of skewed interactions between the host and the gut microbiota and cancer initiation. Even if surgery is the primary therapeutic strategy, patients with advanced disease or cancer recurrence after surgery remain difficult to cure. Therefore, the gut microbiota has been proposed as a novel therapeutic target in light of recent promising data in which it seems to modulate the response to cancer immunotherapy. The use of microbe-targeted therapies, including antibiotics, prebiotics, live biotherapeutics, and fecal microbiota transplantation, is therefore considered to support current therapies in CRC management. In this review, we will discuss the importance of host−microbe interactions in CRC and how promoting homeostatic immune responses through microbe-targeted therapies may be useful in preventing/treating CRC development.

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 Fecal Microbiota Transplantation Prevents Intestinal Injury, Upregulation of Toll-Like Receptors, and 5-Fluorouracil/Oxaliplatin-Induced Toxicity in Colorectal Cancer

2020 ◽  
Vol 21 (2) ◽  
pp. 386 ◽  
Author(s):  
Ching-Wei Chang ◽  
Hung-Chang Lee ◽  
Li-Hui Li ◽  
Jen-Shiu Chiang Chiau ◽  
Tsang-En Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Common Adverse Effect ◽  
Mucosal Injury ◽  
Fecal Microbiota ◽  
Intestinal Injury ◽  
Toll Like Receptors ◽  
Adenocarcinoma Cells ◽  
Intestinal Mucositis

FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin), a 5-fluorouracil (5-FU)-based chemotherapy regimen, is one of most common therapeutic regimens for colorectal cancer. However, intestinal mucositis is a common adverse effect for which no effective preventive strategies exist. Moreover, the efficacy and the safety of fecal microbiota transplants (FMT) in cancer patients treated with anti-neoplastic agents are still scant. We investigated the effect of FMT on FOLFOX-induced mucosal injury. BALB/c mice implanted with syngeneic CT26 colorectal adenocarcinoma cells were orally administered FMT daily during and two days after five-day injection of FOLFOX regimen for seven days. Administration of FOLFOX significantly induced marked levels of diarrhea and intestinal injury. FMT reduced the severity of diarrhea and intestinal mucositis. Additionally, the number of goblet cells and zonula occludens-1 decreased, while apoptotic and NF-κB-positive cells increased following FOLFOX treatment. The expression of toll-like receptors (TLRs), MyD88, and serum IL-6 were upregulated following FOLFOX treatment. These responses were attenuated following FMT. The disrupted fecal gut microbiota composition was also restored by FMT after FOLFOX treatment. Importantly, FMT did not cause bacteremia and safely alleviated FOLFOX-induced intestinal mucositis in colorectal cancer-bearing mice. The putative mechanism may involve the gut microbiota TLR-MyD88-NF-κB signaling pathway in mice with implanted colorectal carcinoma cells.

scholarly journals Therapeutic methods of gut microbiota modification in colorectal cancer management – fecal microbiota transplantation, prebiotics, probiotics, and synbiotics

Gut Microbes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 1518-1530 ◽  
Author(s):  
Karolina Kaźmierczak-Siedlecka ◽  
Agnieszka Daca ◽  
Mateusz Fic ◽  
Thierry van de Wetering ◽  
Marcin Folwarski ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Cancer Management

Gut Microbiota as a Therapeutic Target for Metabolic Disorders

2018 ◽  
Vol 25 (9) ◽  
pp. 984-1001 ◽  
Author(s):  
Hirofumi Okubo ◽  
Yusuke Nakatsu ◽  
Akifumi Kushiyama ◽  
Takeshi Yamamotoya ◽  
Yasuka Matsunaga ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Therapeutic Target ◽  
Metabolic Disorders ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Vital Role ◽  
Alcoholic Fatty Liver ◽  
Beneficial Effects ◽  
New Treatment ◽  
Underlying Mechanisms

Background: Gut microbiota play a vital role not only in the digestion and absorption of nutrients, but also in homeostatic maintenance of host immunity, metabolism and the gut barrier. Recent evidence suggests that gut microbiota alterations contribute to the pathogenesis of metabolic disorders. Objective and Method: In this review, we discuss the association between the gut microbiota and metabolic disorders, such as obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease, and the contribution of relevant modulating interventions, focusing on recent human studies. Results: Several studies have identified potential causal associations between gut microbiota and metabolic disorders, as well as the underlying mechanisms. The effects of modulating interventions, such as prebiotics, probiotics, fecal microbiota transplantation, and other new treatment possibilities on these metabolic disorders have also been reported. Conclusion: A growing body of evidence highlights the role of gut microbiota in the development of dysbiosis, which in turn influences host metabolism and disease phenotypes. Further studies are required to elucidate the precise mechanisms by which gut microbiota-derived mediators induce metabolic disorders and modulating interventions exert their beneficial effects in humans. The gut microbiota represents a novel potential therapeutic target for a range of metabolic disorders.

scholarly journals Pancreatic Diseases and Microbiota: A Literature Review and Future Perspectives

2020 ◽  
Vol 9 (11) ◽  
pp. 3535
Author(s):  
Marcantonio Gesualdo ◽  
Felice Rizzi ◽  
Silvia Bonetto ◽  
Stefano Rizza ◽  
Federico Cravero ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Current Knowledge ◽  
Research Area ◽  
Fecal Microbiota ◽  
Pancreatic Diseases ◽  
Rheumatologic Diseases ◽  
Inflammatory Bowel ◽  
Irritable Bowel ◽  
The One

Gut microbiota represent an interesting worldwide research area. Several studies confirm that microbiota has a key role in human diseases, both intestinal (such as inflammatory bowel disease, celiac disease, intestinal infectious diseases, irritable bowel syndrome) and extra intestinal disorders (such as autism, multiple sclerosis, rheumatologic diseases). Nowadays, it is possible to manipulate microbiota by administering prebiotics, probiotics or synbiotics, through fecal microbiota transplantation in selected cases. In this scenario, pancreatic disorders might be influenced by gut microbiota and this relationship could be an innovative and inspiring field of research. However, data are still scarce and controversial. Microbiota manipulation could represent an important therapeutic strategy in the pancreatic diseases, in addition to standard therapies. In this review, we analyze current knowledge about correlation between gut microbiota and pancreatic diseases, by discussing on the one hand existing data and on the other hand future possible perspectives.

scholarly journals Fecal Microbiota Transplantation in Patients with HBV Infection or Other Chronic Liver Diseases: Update on Current Knowledge and Future Perspectives

2021 ◽  
Vol 10 (12) ◽  
pp. 2605
Author(s):  
Mattia Paratore ◽  
Francesco Santopaolo ◽  
Giovanni Cammarota ◽  
Maurizio Pompili ◽  
Antonio Gasbarrini ◽  
...  
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Current Knowledge ◽  
Fecal Microbiota ◽  
Clinical Settings ◽  
Gut Dysbiosis ◽  
Bidirectional Relationship ◽  
Cirrhotic Patients ◽  
Gut Microbiota Composition

Liver disease and gut dysbiosis are strictly associated, and the pathophysiology of this bidirectional relationship has recently been the subject of several investigations. Growing evidence highlights the link between gut microbiota composition, impairment of the gut-liver axis, and the development or progression of liver disease. Therefore, the modulation of gut microbiota to maintain homeostasis of the gut-liver axis could represent a potential instrument to halt liver damage, modify the course of liver disease, and improve clinical outcomes. Among all the methods available to achieve this purpose, fecal microbiota transplantation (FMT) is one of the most promising, being able to directly reshape the recipient’s gut microbial communities. In this review, we report the main characteristics of gut dysbiosis and its pathogenetic consequences in cirrhotic patients, discussing the emerging data on the application of FMT for liver disease in different clinical settings.

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