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Frontiers in Immunology 2020The intestinal microbiota, composed of a large population of microorganisms, is often considered a "forgotten organ" in human health and diseases. Increasing evidence... (Review)
Review
The intestinal microbiota, composed of a large population of microorganisms, is often considered a "forgotten organ" in human health and diseases. Increasing evidence indicates that dysbiosis of the intestinal microbiota is closely related to colorectal cancer (CRC). The roles for intestinal microorganisms that initiated and facilitated the CRC process are becoming increasingly clear. Hypothesis models have been proposed to illustrate the complex relationship between the intestinal microbiota and CRC. Recent studies have identified , enterotoxigenic , , , , and as CRC candidate pathogens. In this review, we summarized the mechanisms involved in microbiota-related colorectal carcinogenesis, including inflammation, pathogenic bacteria, and their virulence factors, genotoxins, oxidative stress, bacterial metabolites, and biofilm. We also described the clinical values of intestinal microbiota and novel strategies for preventing and treating CRC.
Topics: Adenocarcinoma; Animals; Bacteria; Biodiversity; Biofilms; Carcinogenesis; Cell Transformation, Neoplastic; Colorectal Neoplasms; Diet; Gastrointestinal Microbiome; Genes, APC; Humans; Inflammation; Mice; Models, Biological; Mutagens; Neoplastic Syndromes, Hereditary; Oxidative Stress; Rats; Virulence
PubMed: 33329610
DOI: 10.3389/fimmu.2020.615056 -
Science (New York, N.Y.) Apr 2024A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater...
A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D-induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival. In mice, resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of , which positively regulates cancer immunity. Our findings indicate a previously unappreciated connection between vitamin D, microbial commensal communities, and immune responses to cancer. Collectively, they highlight vitamin D levels as a potential determinant of cancer immunity and immunotherapy success.
Topics: Animals; Female; Humans; Male; Mice; Bacteroides fragilis; Gastrointestinal Microbiome; Immune Checkpoint Inhibitors; Immunotherapy; Intestinal Mucosa; Mice, Inbred C57BL; Neoplasms; Vitamin D; Diet; Cell Line, Tumor; Calcifediol; Vitamin D-Binding Protein
PubMed: 38662827
DOI: 10.1126/science.adh7954 -
Gut Microbes 2023The etiology of colorectal cancer (CRC) is influenced by bacterial communities that colonize the gastrointestinal tract. These microorganisms derive essential nutrients... (Review)
Review
The etiology of colorectal cancer (CRC) is influenced by bacterial communities that colonize the gastrointestinal tract. These microorganisms derive essential nutrients from indigestible dietary or host-derived compounds and activate molecular signaling pathways necessary for normal tissue and immune function. Associative and mechanistic studies have identified bacterial species whose presence may increase CRC risk, including notable examples such as , Enterotoxigenic , and pks . In recent years this work has expanded in scope to include aspects of host mutational status, intra-tumoral microbial heterogeneity, transient infection, and the cumulative influence of multiple carcinogenic bacteria after sequential or co-colonization. In this review, we will provide an updated overview of how host-bacteria interactions influence CRC development, how this knowledge may be utilized to diagnose or prevent CRC, and how the gut microbiome influences CRC treatment efficacy.
Topics: Humans; Colorectal Neoplasms; Escherichia coli; Gastrointestinal Microbiome; Fusobacterium nucleatum; Bacterial Infections
PubMed: 36927206
DOI: 10.1080/19490976.2023.2185028 -
World Journal of Gastroenterology Aug 2022The gut microbiota is a complex community of microorganisms that inhabit the digestive tracts of humans, living in symbiosis with the host. Dysbiosis, characterized by... (Review)
Review
The gut microbiota is a complex community of microorganisms that inhabit the digestive tracts of humans, living in symbiosis with the host. Dysbiosis, characterized by an imbalance between the beneficial and opportunistic gut microbiota, is associated with several gastrointestinal disorders, such as irritable bowel syndrome (IBS); inflammatory bowel disease (IBD), represented by ulcerative colitis and Crohn's disease; and colorectal cancer (CRC). Dysbiosis can disrupt the mucosal barrier, resulting in perpetuation of inflammation and carcinogenesis. The increase in some specific groups of harmful bacteria, such as () and enterotoxigenic (ETBF), has been associated with chronic tissue inflammation and the release of pro-inflammatory and carcinogenic mediators, increasing the chance of developing CRC, following the inflammation-dysplasia-cancer sequence in IBD patients. Therefore, the aim of the present review was to analyze the correlation between changes in the gut microbiota and the development and maintenance of IBD, CRC, and IBD-associated CRC. Patients with IBD and CRC have shown reduced bacterial diversity and abundance compared to healthy individuals, with enrichment of and . Specific bacteria are also associated with the onset and progression of CRC, such as , , , , and ETBF. Future research can evaluate the advantages of modulating the gut microbiota as preventive measures in CRC high-risk patients, directly affecting the prognosis of the disease and the quality of life of patients.
Topics: Bacteria; Bacteroides fragilis; Colorectal Neoplasms; Dysbiosis; Escherichia coli; Gastrointestinal Microbiome; Humans; Inflammation; Inflammatory Bowel Diseases; Quality of Life; Sand
PubMed: 36157114
DOI: 10.3748/wjg.v28.i30.4053 -
Nature Communications Oct 2022Renal fibrosis is an inevitable outcome of various manifestations of progressive chronic kidney diseases (CKD). The need for efficacious treatment regimen against renal...
Renal fibrosis is an inevitable outcome of various manifestations of progressive chronic kidney diseases (CKD). The need for efficacious treatment regimen against renal fibrosis can therefore not be overemphasized. Here we show a novel protective role of Bacteroides fragilis (B. fragilis) in renal fibrosis in mice. We demonstrate decreased abundance of B. fragilis in the feces of CKD patients and unilateral ureteral obstruction (UUO) mice. Oral administration of live B. fragilis attenuates renal fibrosis in UUO and adenine mice models. Increased lipopolysaccharide (LPS) levels are decreased after B. fragilis administration. Results of metabolomics and proteomics studies show decreased level of 1,5-anhydroglucitol (1,5-AG), a substrate of SGLT2, which increases after B. fragilis administration via enhancement of renal SGLT2 expression. 1,5-AG is an agonist of TGR5 that attenuates renal fibrosis by inhibiting oxidative stress and inflammation. Madecassoside, a natural product found via in vitro screening promotes B. fragilis growth and remarkably ameliorates renal fibrosis. Our findings reveal the ameliorative role of B. fragilis in renal fibrosis via decreasing LPS and increasing 1,5-AG levels.
Topics: Adenine; Animals; Bacteroides fragilis; Biological Products; Disease Models, Animal; Fibrosis; Gastrointestinal Microbiome; Kidney; Kidney Diseases; Lipopolysaccharides; Mice; Renal Insufficiency, Chronic; Sodium-Glucose Transporter 2; Ureteral Obstruction
PubMed: 36241632
DOI: 10.1038/s41467-022-33824-6 -
Journal of Food and Drug Analysis Jul 2019Studies on the role of gut commensal bacteria in health development have rapidly attracted much more attention beyond the classical pathogens over the last decade. Many... (Review)
Review
Studies on the role of gut commensal bacteria in health development have rapidly attracted much more attention beyond the classical pathogens over the last decade. Many important reports have highlighted the changes in the gut microbiota (dysbiosis) are closely related to development of intra- and extra-intestinal, chronic inflammation related diseases such as colitis, obesity/metabolic syndromes, diabetes mellitus, liver diseases, cardiovascular diseases and also cancer and neurodegenerative diseases. To circumvent these difficulties, the strategy of modulating the structure of the gut microbiota has been under intensive study and shed more light on amelioration of these inflammation related diseases. While traditional probiotics generally show marginal ameliorative effects, emerging next generation probiotics start to reveal as new preventive and therapeutic tools. Recent studies have unraveled many potential next generation probiotics (NGP). These include Prevotella copri and Christensenella minuta that control insulin resistance, Parabacteroides goldsteinii, Akkermansia muciniphila and Bacteroides thetaiotaomicron that reverse obesity and insulin resistance, Faecalibacterium prausnitzii that protects mice against intestinal diseases, and Bacteroides fragilis that reduces inflammation and shows anticancer effect. New agents will soon be revealed for targeted therapy on specific inflammation related diseases. The important roles of next generation probiotics and gut microbiota normobiosis on the maintenance of intestinal integrity and homeostasis are emphasized.
Topics: Animals; Cardiovascular Diseases; Colitis; Diabetes Mellitus; Gastrointestinal Microbiome; Humans; Inflammation; Liver Diseases; Metabolic Syndrome; Neoplasms; Neurodegenerative Diseases; Obesity; Probiotics
PubMed: 31324278
DOI: 10.1016/j.jfda.2018.12.011 -
Role of the Gut Microbiota and Its Metabolites in Tumorigenesis or Development of Colorectal Cancer.Advanced Science (Weinheim,... Aug 2023Colorectal cancer (CRC) is the most common cancer of the digestive system with high mortality and morbidity rates. Gut microbiota is found in the intestines, especially... (Review)
Review
Colorectal cancer (CRC) is the most common cancer of the digestive system with high mortality and morbidity rates. Gut microbiota is found in the intestines, especially the colorectum, and has structured crosstalk interactions with the host that affect several physiological processes. The gut microbiota include CRC-promoting bacterial species, such as Fusobacterium nucleatum, Escherichia coli, and Bacteroides fragilis, and CRC-protecting bacterial species, such as Clostridium butyricum, Streptococcus thermophilus, and Lacticaseibacillus paracasei, which along with other microorganisms, such as viruses and fungi, play critical roles in the development of CRC. Different bacterial features are identified in patients with early-onset CRC, combined with different patterns between fecal and intratumoral microbiota. The gut microbiota may be beneficial in the diagnosis and treatment of CRC; some bacteria may serve as biomarkers while others as regulators of chemotherapy and immunotherapy. Furthermore, metabolites produced by the gut microbiota play essential roles in the crosstalk with CRC cells. Harmful metabolites include some primary bile acids and short-chain fatty acids, whereas others, including ursodeoxycholic acid and butyrate, are beneficial and impede tumor development and progression. This review focuses on the gut microbiota and its metabolites, and their potential roles in the development, diagnosis, and treatment of CRC.
Topics: Humans; Gastrointestinal Microbiome; Colorectal Neoplasms; Carcinogenesis; Cell Transformation, Neoplastic; Bacteria; Escherichia coli
PubMed: 37263983
DOI: 10.1002/advs.202205563 -
Gut Microbes 2022Gut microbiota and its association with cancer development/treatment has been intensively studied during the past several years. Currently, there is a growing interest... (Review)
Review
Gut microbiota and its association with cancer development/treatment has been intensively studied during the past several years. Currently, there is a growing interest toward next-generation probiotics (NGPs) as therapeutic agents that alter gut microbiota and impact on cancer development. In the present review we focus on three emerging NGPs, namely , and as their presence in the digestive tract can have an impact on cancer incidence. These NGPs enhance gastrointestinal immunity, maintain intestinal barrier integrity, produce beneficial metabolites, act against pathogens, improve immunotherapy efficacy, and reduce complications associated with chemotherapy and radiotherapy. Notably, the use of NGPs in cancer patients does not have a long history and, although their safety remains relatively undefined, recently published data has shown that they are non-toxigenic. Notwithstanding, may promote colitis whereas enterotoxigenic stimulates chronic inflammation and participates in colorectal carcinogenesis. Nevertheless, the majority of strains provide a beneficial effect to the host, are non-toxigenic and considered as the best current NGP candidate. Overall, emerging studies indicate a beneficial role of these NGPs in the prevention of carcinogenesis and open new promising therapeutic options for cancer patients.
Topics: Animals; Antineoplastic Agents; Combined Modality Therapy; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Neoplasms; Probiotics
PubMed: 35167406
DOI: 10.1080/19490976.2022.2035659 -
The Journal of Clinical Investigation Feb 2022The importance of the microbiota in the development of colorectal cancer (CRC) is increasingly evident, but identifying specific microbial features that influence CRC... (Review)
Review
The importance of the microbiota in the development of colorectal cancer (CRC) is increasingly evident, but identifying specific microbial features that influence CRC initiation and progression remains a central task for investigators. Studies determining the microbial mechanisms that directly contribute to CRC development or progression are revealing bacterial factors such as toxins that contribute to colorectal carcinogenesis. However, even when investigators have identified bacteria that express toxins, questions remain about the host determinants of a toxin's cancer-potentiating effects. For other cancer-correlating bacteria that lack toxins, the challenge is to define cancer-relevant virulence factors. Herein, we evaluate three CRC-correlating bacteria, colibactin-producing Escherichia coli, enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum, for their virulence features relevant to CRC. We also consider the beneficial bioactivity of gut microbes by highlighting a microbial metabolite that may enhance CRC antitumor immunity. In doing so, we aim to elucidate unique and shared mechanisms underlying the microbiota's contributions to CRC and to accelerate investigation from target validation to CRC therapeutic discovery.
Topics: Animals; Bacteria; Carcinogenesis; Colorectal Neoplasms; Gastrointestinal Microbiome; Humans
PubMed: 35166235
DOI: 10.1172/JCI155101 -
Nature Communications Mar 2023Intrahepatic cholestasis of pregnancy (ICP) is a female pregnancy-specific disorder that is characterized by increased serum bile acid and adverse fetal outcomes. The...
Intrahepatic cholestasis of pregnancy (ICP) is a female pregnancy-specific disorder that is characterized by increased serum bile acid and adverse fetal outcomes. The aetiology and mechanism of ICP are poorly understood; thus, existing therapies have been largely empiric. Here we show that the gut microbiome differed significantly between individuals with ICP and healthy pregnant women, and that colonization with gut microbiome from ICP patients was sufficient to induce cholestasis in mice. The gut microbiomes of ICP patients were primarily characterized by Bacteroides fragilis (B. fragilis), and B. fragilis was able to promote ICP by inhibiting FXR signaling via its BSH activity to modulate bile acid metabolism. B. fragilis-mediated FXR signaling inhibition was responsible for excessive bile acid synthesis and interrupted hepatic bile excretion to ultimately promote the initiation of ICP. We propose that modulation of the gut microbiota-bile acid-FXR axis may be of value for ICP treatment.
Topics: Female; Pregnancy; Humans; Animals; Mice; Gastrointestinal Microbiome; Cholestasis, Intrahepatic; Pregnancy Complications; Bile Acids and Salts
PubMed: 36894566
DOI: 10.1038/s41467-023-36981-4