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 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 Th17/Treg Cell Balance: A Gut Microbiota-Modulated Story

2019 ◽  
Vol 7 (12) ◽  
pp. 583 ◽  
Author(s):  
Hongyu Cheng ◽  
Xiong Guan ◽  
Dekun Chen ◽  
Wentao Ma
Keyword(s):  
Gut Microbiota ◽  
Treg Cell ◽  
Immune Cells ◽  
Intestinal Tract ◽  
Therapeutic Potential ◽  
Fecal Microbiota Transplantation ◽  
Treg Cells ◽  
Fecal Microbiota ◽  
Adaptive Immune ◽  
Cell Balance

The intestinal tract of vertebrates is normally colonized with a remarkable number of commensal microorganisms that are collectively referred to as gut microbiota. Gut microbiota has been demonstrated to interact with immune cells and to modulate specific signaling pathways involving both innate and adaptive immune processes. Accumulated evidence suggests that the imbalance of Th17 and Treg cells is associated with the development of many diseases. Herein, we emphatically present recent findings to show how specific gut microbiota organisms and metabolites shape the balance of Th17 and Treg cells. We also discuss the therapeutic potential of fecal microbiota transplantation (FMT) in diseases caused by the imbalance of Th17 and Treg cells

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

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 Malnutrition Accelerates Colorectal Cancer Progression through Macrophage Activated by B Cells Immune via Gut Microbiota

2020 ◽  
Author(s):  
Xu Chao ◽  
Li Dechuan ◽  
Wang Ziwei ◽  
Wang Yan ◽  
Xu Lu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
B Cells ◽  
Gut Microbiota ◽  
Cancer Progression ◽  
Gut Microbiome ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Nutrition Status ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mice Model

Abstract Background: Malnutrition threatened the clinical outcomes of colorectal cancer (CRC) by reducing patients’ responses to anti-cancer treatments and ultimately shortening thesurvival time. Recently malnutrition has been confirmed to play an important role in CRC progress via gut microbiota. However, roles of gut microbiota in the immunopathogenesis of malnutrition and its underlying mechanisms remain inconclusive. Methods: Patient-Generated Subjective Global Assessment (PG-SGA) was performed to determine the nutrition status in colon cancer patients. 16srRNA sequencing was prepared to explore the dramatic variation of the fecal microbiota among patients with different nutrition status. Fecal microbiota transplantation was used to transplant into C57BL/6J mice model and DSS/AOM mice model. Immunohistochemistry and immunofluorescence were applied to test the CD makers. Fluorescence-activated cell sorting was also prepared to explore the B cells and macrophage from serum and tissues. Enzyme-linked immunosorbent assay and qPCR were used to determine the expression level of cytokines.Results: In this work, we found the specific microbiota species including Atopobium.vaginae, Selenomonas.sputigena and Faecalibacterium.prausnitzii, which may be considered as the diagnostic biomarkers to help improve poor prognosis in CRC. These microbiota were found to be protumorigenic and adversely affect the nutritional status and overall survival of the animal models. More importantly, our evidence suggesting that these fecal microbiota recruited B cells and macrophage to activate the specific tumor immune in CRC. Depletion of B cells significantly suppressed fecal microbiota induced-M2b polarization, as well as the protumorigenic activity of tumor-associated macrophages in vivo.Conclusion: gut microbiome in CRC under malnutrition status could upregulate the activity of B cells and protumorigenic macrophage in CRC. Gut microbiome intervention could be a feasible approach to malnutrition-related CRC treatment.

scholarly journals Gut microbiota density influences host physiology and is shaped by host and microbial factors

2018 ◽  
Author(s):  
Eduardo J. Contijoch ◽  
Graham J. Britton ◽  
Chao Yang ◽  
Ilaria Mogno ◽  
Zhihua Li ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Carrying Capacity ◽  
Ileal Pouch ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Therapeutic Interventions ◽  
Immune Homeostasis ◽  
Targeted Therapeutics ◽  
Anal Anastomosis ◽  
The Impact

SummaryTo identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic features of the host (carrying capacity) and the fitness of the gut microbiota shape microbiota density. Therapeutic manipulation of microbiota density in mice altered host metabolic and immune homeostasis. In humans, gut microbiota density was reduced in Crohn’s disease, ulcerative colitis, and ileal pouch-anal anastomosis. The gut microbiota in recurrent Clostridium difficile infection had lower density and reduced fitness that were restored by fecal microbiota transplantation. Understanding the interplay between microbiota and disease in terms of microbiota density, host carrying capacity, and microbiota fitness provide new insights into microbiome structure and microbiome targeted therapeutics.

scholarly journals Gut microbiota density influences host physiology and is shaped by host and microbial factors

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Eduardo J Contijoch ◽  
Graham J Britton ◽  
Chao Yang ◽  
Ilaria Mogno ◽  
Zhihua Li ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Carrying Capacity ◽  
Ileal Pouch ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Therapeutic Interventions ◽  
Editorial Note ◽  
Targeted Therapeutics ◽  
Recurrent Clostridium Difficile Infection ◽  
The Impact

To identify factors that regulate gut microbiota density and the impact of varied microbiota density on health, we assayed this fundamental ecosystem property in fecal samples across mammals, human disease, and therapeutic interventions. Physiologic features of the host (carrying capacity) and the fitness of the gut microbiota shape microbiota density. Therapeutic manipulation of microbiota density in mice altered host metabolic and immune homeostasis. In humans, gut microbiota density was reduced in Crohn’s disease, ulcerative colitis, and ileal pouch-anal anastomosis. The gut microbiota in recurrent Clostridium difficile infection had lower density and reduced fitness that were restored by fecal microbiota transplantation. Understanding the interplay between microbiota and disease in terms of microbiota density, host carrying capacity, and microbiota fitness provide new insights into microbiome structure and microbiome targeted therapeutics.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

scholarly journals The gut microbiota in osteoarthritis: where do we stand and what can we do?

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Xiaoxia Hao ◽  
Xingru Shang ◽  
Jiawei Liu ◽  
Ruimin Chi ◽  
Jiaming Zhang ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Musculoskeletal Diseases ◽  
Fecal Microbiota ◽  
Therapeutic Interventions ◽  
Future Research ◽  
Joint Injury ◽  
Potential Biomarker ◽  
Synovial Membrane Inflammation ◽  
Underlying Mechanisms

AbstractOsteoarthritis (OA) is one of the most frequent musculoskeletal diseases characterized by degeneration of articular cartilage, subchondral bone remodeling, and synovial membrane inflammation, which is a leading cause of global disability, morbidity, and decreased quality of life. Interpreting the potential mechanisms of OA pathogenesis is essential for developing novel prevention and disease-modifying therapeutic interventions. Gut microbiota is responsible for a series of metabolic, immunological, and structural and neurological functions, potentially elucidating the heterogeneity of OA phenotypes and individual features. In this narrative review, we summarized research evidence supporting the hypothesis of a “gut-joint axis” and the interaction between gut microbiota and the OA-relevant factors, including age, gender, genetics, metabolism, central nervous system, and joint injury, elucidating the underlying mechanisms of this intricate interaction. In the context, we also speculated the promising manipulation of gut microbiota in OA management, such as exercise and fecal microbiota transplantation (FMT), highlighting the clinical values of gut microbiota. Additionally, future research directions, such as more convincing studies by the interventions of gut microbiota, the gene regulation of host contributing to or attributed to the specific phenotypes of gut microbiota related to OA, and the relevance of distinct cell subgroups to gut microbiota, are expected. Moreover, gut microbiota is also the potential biomarker related to inflammation and gut dysbiosis that is able to predict OA progression and monitor the efficacy of therapeutic intervention.

scholarly journals Microbial Metabolites in Colorectal Cancer: Basic and Clinical Implications

Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 159
Author(s):  
Yao Peng ◽  
Yuqiang Nie ◽  
Jun Yu ◽  
Chi Chun Wong
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Cancer Diagnosis ◽  
Intestinal Tract ◽  
Clinical Applications ◽  
Diagnosis And Treatment ◽  
Clinical Implications ◽  
Microbial Metabolites ◽  
Colorectal Tumorigenesis ◽  
Technology Studies

Colorectal cancer (CRC) is one of the leading cancers that cause cancer-related deaths worldwide. The gut microbiota has been proved to show relevance with colorectal tumorigenesis through microbial metabolites. By decomposing various dietary residues in the intestinal tract, gut microbiota harvest energy and produce a variety of metabolites to affect the host physiology. However, some of these metabolites are oncogenic factors for CRC. With the advent of metabolomics technology, studies profiling microbiota-derived metabolites have greatly accelerated the progress in our understanding of the host-microbiota metabolism interactions in CRC. In this review, we briefly summarize the present metabolomics techniques in microbial metabolites researches and the mechanisms of microbial metabolites in CRC pathogenesis, furthermore, we discuss the potential clinical applications of microbial metabolites in cancer diagnosis and treatment.

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