RESUMEN
The gut microbiota, known as the "forgotten organ" and "human second genome," comprises a complex microecosystem. It significantly influences the development of various tumors, including colorectal, liver, stomach, breast, and lung cancers, through both direct and indirect mechanisms. These mechanisms include the "gut-liver" axis, the "lung-intestine" axis, and interactions with the immune system. The intestinal flora exhibits dual roles in cancer, both promoting and suppressing its progression. Traditional Chinese medicine (TCM) can alter cancer progression by regulating the intestinal flora. It modifies the intestinal flora's composition and structure, along with the levels of endogenous metabolites, thus affecting the intestinal barrier, immune system, and overall body metabolism. These actions contribute to TCM's significant antitumor effects. Moreover, the gut microbiota metabolizes TCM components, enhancing their antitumor properties. Therefore, exploring the interaction between TCM and the intestinal flora offers a novel perspective in understanding TCM's antitumor mechanisms. This paper succinctly reviews the association between gut flora and the development of tumors, including colorectal, liver, gastric, breast, and lung cancers. It further examines current research on the interaction between TCM and intestinal flora, with a focus on its antitumor efficacy. It identifies limitations in existing studies and suggests recommendations, providing insights into antitumor drug research and exploring TCM's antitumor effectiveness. Additionally, this paper aims to guide future research on TCM and the gut microbiota in antitumor studies.
Asunto(s)
Microbioma Gastrointestinal , Medicina Tradicional China , Neoplasias , Humanos , Neoplasias/microbiología , Neoplasias/metabolismo , Neoplasias/tratamiento farmacológico , Animales , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
Inchinkoto (ICKT) is a popular choleretic and hepatoprotective herbal medicine that is widely used in Japan. Geniposide, a major ingredient of ICKT, is metabolized to genipin by gut microbiota, which exerts a choleretic effect. This study investigates the relationship between stool genipin-producing activity and diversity of the clinical effect of ICKT in patients with malignant obstructive jaundice. Fifty-two patients with malignant obstructive jaundice who underwent external biliary drainage were included. ICKT was administered as three packets per day (7.5 g/day) for three days and 2.5 g on the morning of the fourth day. Stool samples were collected before ICKT administration and bile flow was monitored on a daily basis. The microbiome, genipin-producing activity, and organic acids in stools were analyzed. The Shannon-Wiener (SW) index was calculated to evaluate gut microbiome diversity. The stool genipin-producing activity showed a significant positive correlation with the SW index. Stool genipin-producing activity positively correlated with the order Clostridia (obligate anaerobes), but negatively correlated with the order Lactobacillales (facultative anaerobes). Moreover, stool genipin-producing activity was positively correlated to the concentration valeric acid, but negatively correlated to the concentration of lactic acid and succinic acid. The change of bile flow at 2 and 3 days after ICKT administration showed significant positive correlation with genipin-producing activity (correlation coefficient, 0.40 and 0.29, respectively, P < 0.05). An analysis of stool profile, including stool genipin-producing activity, may predict the efficacy of ICKT. Modification of the microbiome may be a target to enhance the therapeutic effect of ICKT.
Asunto(s)
Colagogos y Coleréticos/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Heces/química , Microbioma Gastrointestinal/efectos de los fármacos , Iridoides/metabolismo , Ictericia Obstructiva/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Bilis/química , Ácidos Carboxílicos/metabolismo , Clostridium/genética , Clostridium/metabolismo , Femenino , Microbioma Gastrointestinal/genética , Humanos , Ictericia Obstructiva/microbiología , Lactobacillales/genética , Lactobacillales/metabolismo , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/microbiología , Resultado del TratamientoRESUMEN
The human body and its microbiome constitute a highly delicate system. The gut microbiome participates in the absorption of the host's nutrients and metabolism, maintains the microcirculation, and modulates the immune response. Increasing evidence shows that gut microbiome dysbiosis in the body not only affects the occurrence and development of tumors but also tumor prognosis and treatment. Microbiome have been implicated in tumor control in patients undergoing anti- angiogenesis therapy and immunotherapy. In cases with unsatisfactory responses to chemotherapy, radiotherapy, and targeted therapy, appropriate adjustment of microbes abundance is considered to enhance the treatment response. Here, we review the current research progress in cancer immunotherapy and anti- angiogenesis therapy, as well as the unlimited potential of their combination, especially focusing on how the interaction between intestinal microbiota and the immune system affects cancer pathogenesis and treatment. In addition, we discuss the effects of microbiota on anti-cancer immune response and anti- angiogenesis therapy, and the potential value of these interactions in promoting further research in this field.
Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Inmunoterapia , Microbiota , Neoplasias/terapia , Inhibidores de la Angiogénesis/farmacología , Carcinogénesis/inmunología , Ensayos Clínicos Fase III como Asunto , Terapia Combinada , Dieta , Medicamentos Herbarios Chinos/farmacología , Disbiosis/inmunología , Disbiosis/metabolismo , Humanos , Inhibidores de Puntos de Control Inmunológico , Microbiota/efectos de los fármacos , Microbiota/inmunología , Microbiota/fisiología , Neoplasias/irrigación sanguínea , Neoplasias/inmunología , Neoplasias/microbiología , Probióticos , Simbiosis , Escape del TumorRESUMEN
There are various important factors in reducing the risk of cancer development and progression; these factors may correct an unbalanced intake of nutrients to maintain the living body's homeostasis, detoxify toxic materials, acting as an external factor, and maintain and strengthen the body's immune function. In a normal cell environment, nutrients, such as carbohydrates, lipids, proteins, vitamins, and minerals, are properly digested and absorbed into the body, and, as a result, an environment in which cancer can develop and progress is prevented. It is necessary to prevent toxic materials from entering the body and to detoxify poisons in the body. If these processes occur correctly, cells work normally, and genes cannot be damaged. The most important factor in the fight against cancer and prevention of the development and progression of cancer is the immune system. This requires a nutritional state in which the immune system works well, allowing the intestinal microbiome to carry out all of its roles. In order to grow intestinal microbiota, the consumption of prebiotics, such as organic vegetables, fruits, and dietary fiber, and probiotics of effective intestinal microbiota, such as fermented foods and supplements, is required. Symbiosis, in which these organisms work together, is an effective means of reducing the risk of cancer. In addition, fecal microbiota transplantation (FMT) using ultrafine bubble water, produced specially by the Association for Clinical Research of Fecal Microbiota Transplantation Japan, is also useful for improving the nutritional condition and reducing the risk of cancer.
Asunto(s)
Microbioma Gastrointestinal , Neoplasias/epidemiología , Neoplasias/microbiología , Estado Nutricional , Disbiosis/microbiología , Trasplante de Microbiota Fecal , Humanos , Factores de RiesgoRESUMEN
Cancer affects millions of individuals worldwide. Thus, there is an increased need for the development of novel effective therapeutic approaches. Tumorigenesis is often coupled with immunosuppression which defeats the anticancer immune defense mechanisms activated by the host. Novel anticancer therapies based on the use of immune checkpoint inhibitors (ICIs) are very promising against both solid and hematological tumors, although still exhibiting heterogeneous efficacy, as well as tolerability. Such a differential response seems to derive from individual diversity, including the gut microbiota (GM) composition of specific patients. Experimental evidence supports the key role played by the GM in the activation of the immune system response against malignancies. This observation suggests to aim for patienttailored complementary therapies able to modulate the GM, enabling the selective enrichment in microbial species, which can improve the positive outcome of ICIbased immunotherapy. Moreover, the research of GMderived predictive biomarkers may help to identify the selected cancer population, which can benefit from ICIbased therapy, without the occurrence of adverse reactions and/or cancer relapse. The present review summarizes the landmark studies published to date, which have contributed to uncovering the tight link existing between GM composition, cancer development and the host immune system. Bridging this triangle of interactions may ultimately guide towards the identification of novel biomarkers, as well as integrated and patienttailored anticancer approaches with greater efficacy.
Asunto(s)
Bacterias/inmunología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias/tratamiento farmacológico , Bacterias/efectos de los fármacos , Ensayos Clínicos como Asunto , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Neoplasias/microbiología , Resultado del TratamientoRESUMEN
The human gastrointestinal (GI) tract hosts trillions of microbial inhabitants involved in maintaining intestinal homeostasis, dysbiosis of which provokes a motley of pathogenic and autoimmune disorders. While the mechanisms by which the microbiota modulates human health are manifold, their liberated metabolites from ingested dietary supplements play a crucial role by bidirectionally regulating the expression of micro-ribonucleic acids (miRNAs). miRNAs are small endogenous non-coding RNAs (ncRNAs) that have been confirmed to be involved in an interplay with microbiota to regulate host gene expression. This comprehensive review focuses on key principles of miRNAs, their regulation, and crosstalk with gut microbiota to influence host gene expression in various human disorders, by bringing together important recent findings centric around miRNA-microbiota interactions in diseases along various axis of the gut with other organs. We also attempt to lay emphasis on exploiting the avenues of gut-directed miRNA therapeutics using rudimentary dietary supplements to regulate abnormal host gene expression in diseases, opening doors to an accessible and economical therapeutic strategy.
Asunto(s)
Microbioma Gastrointestinal , Regulación de la Expresión Génica , MicroARNs/genética , Terapéutica , Animales , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/microbiología , Enfermedades Cardiovasculares/terapia , Enfermedades del Sistema Digestivo/genética , Enfermedades del Sistema Digestivo/microbiología , Enfermedades del Sistema Digestivo/terapia , Tracto Gastrointestinal/inmunología , Tracto Gastrointestinal/microbiología , Salud , Humanos , MicroARNs/metabolismo , Neoplasias/genética , Neoplasias/microbiología , Neoplasias/terapia , Enfermedades del Sistema Nervioso/genética , Enfermedades del Sistema Nervioso/microbiología , Enfermedades del Sistema Nervioso/terapiaRESUMEN
Spontaneous tumor regression following bacterial infection has been observed for hundreds of years. These observations along with anecdotal medical findings in 1890s led to the development of Coley's "toxins," consisting of killed Streptococcus pyogenes and Serratia marcescens bacteria, as the first cancer immunotherapy. The use of this approach, however, was not widely accepted at the time especially after the introduction of radiation therapy as a treatment for cancer in the early 1900s. Over the last 30-40 years there has been renewed interest in the use of bacteria to treat human solid tumors. This is based on the observation that various nonpathogenic anaerobic bacteria can infiltrate and replicate within solid tumors when given intravenously. Bacteria tested as potential anticancer agents include the Gram-positive obligate anaerobes Bifidobacterium and Clostridium, as well as the gram-negative facultative anaerobe Salmonella. Recent advances in synthetic biology and clinical success in cancer immunotherapy provide renewed momentum for developing bacteria-based cancer immunotherapy for cancer treatment and should allow greater potential for the development of novel therapeutic approaches for this devastating disease.
Asunto(s)
Terapia Biológica/métodos , Neoplasias/terapia , Interferencia de ARN , Biología Sintética/métodos , Animales , Línea Celular Tumoral , Ensayos Clínicos Fase I como Asunto , Neoplasias del Colon/microbiología , Neoplasias del Colon/terapia , Escherichia coli/genética , Escherichia coli/fisiología , Femenino , Vectores Genéticos/genética , Vectores Genéticos/uso terapéutico , Humanos , Inmunoterapia/métodos , Inmunoterapia/tendencias , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Desnudos , Neoplasias/microbiología , ARN Mensajero/biosíntesis , ARN Mensajero/genética , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/uso terapéutico , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Inducción de Remisión , Salmonella typhimurium/genética , Salmonella typhimurium/fisiología , Especificidad de la Especie , Organismos Libres de Patógenos Específicos , Biología Sintética/tendencias , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Clostridium butyricum is a butyrate-producing human gut symbiont that has been safely used as a probiotic for decades. C. butyricum strains have been investigated for potential protective or ameliorative effects in a wide range of human diseases, including gut-acquired infection, intestinal injury, irritable bowel syndrome, inflammatory bowel disease, neurodegenerative disease, metabolic disease, and colorectal cancer. In this review we summarize the studies on C. butyricum supplementation with special attention to proposed mechanisms for the associated health benefits and the supporting experimental evidence. These mechanisms center on molecular signals (especially butyrate) as well as immunological signals in the digestive system that cascade well beyond the gut to the liver, adipose tissue, brain, and more. The safety of probiotic C. butyricum strains appears well-established. We identify areas where additional human randomized controlled trials would provide valuable further data related to the strains' utility as an intervention.
Asunto(s)
Butiratos/metabolismo , Clostridium butyricum/inmunología , Clostridium butyricum/metabolismo , Inmunidad , Probióticos , Animales , Suplementos Dietéticos , Interacciones Microbiota-Huesped , Humanos , Inflamación/inmunología , Inflamación/microbiología , Síndrome del Colon Irritable/inmunología , Síndrome del Colon Irritable/microbiología , Enfermedades Metabólicas/inmunología , Enfermedades Metabólicas/microbiología , Neoplasias/inmunología , Neoplasias/microbiología , Enfermedades Neurodegenerativas/inmunología , Enfermedades Neurodegenerativas/microbiología , SimbiosisRESUMEN
Cancer is a disease with a high mortality and disability rate. Cancer consists not only of cancer cells, but also of the surrounding microenvironment and tumor microenvironment (TME) constantly interacting with tumor cells to support tumor development and progression. Over the last decade, accumulating evidence has implicated that microbiota profoundly influences cancer initiation and progression. Most research focuses on gut microbiota, for the gut harbors the largest collection of microorganisms. Gut microbiota includes bacteria, viruses, protozoa, archaea, and fungi in the gastrointestinal tract, affecting DNA damage, host immune response and chronic inflammation in various types of cancer (i.e., colon cancer, gastric cancer and breast cancer). Notably, gut dysbiosis can reshape tumor microenvironment and make it favorable for tumor growth. Recently, accumulating studies have attached the importance of traditional Chinese medicine (TCM) to cancer treatments, and the bioactive natural compounds have been considered as potential drug candidates to suppress cancer initiation and development. Interestingly, more recent studies demonstrate that TCM could potentially prevent and suppress early-stage cancer progression through the regulation of gut microbiota. This review is on the purpose of exhausting the significance of gut microbiota in the tumor microenvironment as potential targets of Chinese medicine.
Asunto(s)
Microbioma Gastrointestinal/fisiología , Tracto Gastrointestinal/microbiología , Medicina Tradicional China , Neoplasias/microbiología , Neoplasias/patología , Microambiente Tumoral/fisiología , Daño del ADN , Progresión de la Enfermedad , Interacciones Huésped-Patógeno/inmunología , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/prevención & control , FitoterapiaRESUMEN
The development of a 'smart' drug capable of distinguishing tumor from host cells has been sought for centuries, but the microenvironment of solid tumors continues to confound therapeutics. Solid tumors present several challenges for current oncotherapeutics, including aberrant vascularization, hypoxia, necrosis, abnormally high pH and local immune suppression. While traditional chemotherapeutics are limited by such an environment, oncolytic microbes are drawn to it - having an innate ability to selectively infect, colonize and eradicate solid tumors. Development of an oncolytic species would represent a shift in the cancer therapeutic paradigm, with ramifications reaching from the medical into the socio-economic. Modern genetic engineering techniques could be implemented to customize 'Frankenstein' bacteria with advantageous characteristics from several species.
Lay abstract Side effects of chemotherapeutics are thought to often be a reflection of our inability to target these toxic substances to only cancer cells; hence, scientists have spent centuries searching for alternative treatments that would confine their actions to tumor cells, sparing healthy tissue. Unfortunately, the dense nature of tumor tissue along with altered blood vessels, that lead to diminished tumor tissue oxygenation, altered tissue pH and cellular metabolic inactivity or even cell death have proven challenging. Importantly, these barriers have contributed to local and even sometimes systemic suppression of the patient's immune system that can allow the tumor to grow and progress unchecked. While most non-cancer cells are inhibited by the local tumor environment, certain microbes, including some bacteria and viruses, are drawn to it, possessing a natural ability to selectively infect, colonize and eradicate solid tumors. These microbes may also restore the patient's immune balance. However, use of these microbes is not without its own problems; nevertheless, modern genetic engineering techniques could be implemented to develop customized, safe, effective bacteria with advantageous characteristics. The development and clinical translation of cancer-fighting bacteria would represent a shift in cancer therapeutics and would have ramifications that reach beyond medical efficacy into the realm of socioeconomics. This review seeks to marry the current field of oncolytic bacteria with the expanding field of modern bacterial genetic engineering techniques in prospect of such a therapeutic.
Asunto(s)
Bacterias , Terapia Biológica , Ingeniería Genética , Neoplasias/terapia , Animales , Bacterias/clasificación , Bacterias/genética , Fenómenos Fisiológicos Bacterianos , Genoma Bacteriano/genética , Interacciones Microbiota-Huesped , Humanos , Neoplasias/microbiología , Microambiente TumoralRESUMEN
Intestinal flora is essential for maintaining host health and plays a unique role in transforming Traditional Chinese Medicine (TCM). TCM, as a bodyguard, has saved countless lives and maintained human health in the long history, especially in this COVID-19 pandemic. Pains of diseases have been removed from the effective TCM therapy, such as TCM preparation, moxibustion, and acupuncture. With the development of life science and technology, the wisdom and foresight of TCM has been more displayed. Furthermore, TCM has been also inherited and developed in innovation to better realize the modernization and globalization. Nowadays, intestinal flora transforming TCM and TCM targeted intestinal flora treating diseases have been important findings in life science. More and more TCM researches showed the significance of intestinal flora. Intestinal flora is also a way to study TCM to elucidate the profound theory of TCM. Processing, compatibility, and properties of TCM are well demonstrated by intestinal flora. Thus, it is no doubt that intestinal flora is a core in TCM study. The interaction between intestinal flora and TCM is so crucial for host health. Therefore, it is necessary to sum up the latest results in time. This paper systematically depicted the profile of TCM and the importance of intestinal flora in host. What is more, we comprehensively summarized and discussed the latest progress of the interplay between TCM and intestinal flora to better reveal the core connotation of TCM.
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Medicamentos Herbarios Chinos/uso terapéutico , Disbiosis/microbiología , Microbioma Gastrointestinal , Medicina Tradicional China , Enfermedades Autoinmunes/microbiología , Enfermedades Autoinmunes/terapia , COVID-19 , Enfermedades Cardiovasculares/microbiología , Enfermedades Cardiovasculares/terapia , Diabetes Mellitus/microbiología , Diabetes Mellitus/terapia , Electroacupuntura , Enfermedades Gastrointestinales/microbiología , Enfermedades Gastrointestinales/terapia , Humanos , Enfermedades Metabólicas/microbiología , Enfermedades Metabólicas/terapia , Neoplasias/microbiología , Neoplasias/terapia , Enfermedad del Hígado Graso no Alcohólico/microbiología , Enfermedad del Hígado Graso no Alcohólico/terapia , Obesidad/microbiología , Obesidad/terapia , Insuficiencia Renal Crónica/microbiología , Insuficiencia Renal Crónica/terapia , SARS-CoV-2RESUMEN
Cancer persists as a major health catastrophe and a leading cause of widespread mortality across every nation. Research of several decades has increased our understanding of the pivotal pathways and key players of the host during tumor development and progression, which has enabled generation of precision therapeutics with improved efficacy. Despite such tremendous advancements in our combat against this fatal disease, a majority of the cancer patients suffer from poor tumor- free survival owing to the increased incidence of recurrent tumor. This is primarily due to the development of resistance against contemporary anti- cancer strategies. Recent studies have pointed towards the involvement of the human symbiotic gut microbiota in regulating the outcome of chemotherapy and immunotherapy. It does so primarily by modulating the metabolism of the drugs and host immune response, thereby enhancing the efficacy and ameliorating the toxicity. The interactions between the therapeutic agents, microbial community and host immunity may provide a new avenue for the clinical management of cancer. In addition, consumption of dietary pro-, pre- and synbiotics has been recognized to confer protection against tumor genesis and also promote improved response to traditional tumor suppressive strategies. Naturally, the use of various combinatorial regimes containing dietary supplements that improve the gut microbiome in amalgamation with conventional cancer treatment methods may significantly augment the therapeutic outcome of cancer patients and circumnavigate the resistance mechanisms that confound traditional therapies. In this review, we have summarized the role of the gut microbiome, which is the largest assembly of commensals within the human body, in regulating the efficacy and toxicity of various existing anti- cancer therapies including chemotherapy, immunotherapy and surgery. Furthermore, we have discussed how novel strategies integrating the application of probiotics, prebiotics, synbiotics and antibiotics in combination with the aforementioned anti- cancer modules manipulate the gut microbiota and, therefore, augment their therapeutic outcome. Together, such innovative anti- tumorigenic approaches may prove highly effective in improving the prognosis of cancer patients.
Asunto(s)
Antineoplásicos/administración & dosificación , Microbioma Gastrointestinal , Neoplasias/tratamiento farmacológico , Prebióticos/administración & dosificación , Animales , Humanos , Neoplasias/microbiologíaRESUMEN
The commensal microbiome of humans has co-evolved for thousands of years. The microbiome regulates human health and is also linked to several diseases, including cancer. The advances in next-generation sequencing have significantly contributed to our understanding of the microbiome and its association with cancer and cancer therapy. Recent studies have highlighted a close relationship of the microbiome to the pharmacological effect of chemotherapy and immunotherapy. The chemo-drugs usually interfere with the host immune system and reduces the microbiome diversity inside the body, which in turn leads to decreased efficacy of these drugs. The human microbiome, specifically the gut microbiome, increases the potency of chemo-drugs through metabolism, enzymatic degradation, ecological differences, and immunomodulation. Recent research exploits the involvement of microbiome to shape the efficacy and decrease the toxicity of these chemo-drugs. In this review, we have highlighted the recent development in understanding the relationship of the human microbiome with cancer and also emphasize on various roles of the microbiome in the modulation of cancer therapy. Additionally, we also summarize the ongoing research focussed on the improved efficacy of chemotherapy and immunotherapy using the host microbiome.
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Antineoplásicos/administración & dosificación , Microbioma Gastrointestinal , Interacciones Microbiota-Huesped , Inmunoterapia/métodos , Neoplasias/tratamiento farmacológico , Prebióticos/administración & dosificación , Animales , Humanos , Inmunomodulación , Neoplasias/inmunología , Neoplasias/microbiologíaRESUMEN
The microbiota influences human health and the development of diverse diseases, including cancer. Microbes can influence tumor initiation and development in either a positive or negative manner. In addition, the composition of the gut microbiota affects the efficacy and toxicity of cancer therapeutics as well as therapeutic resistance. The striking impact of microbiota on oncogenesis and cancer therapy provides compelling evidence to support the notion that manipulating microbial networks represents a promising strategy for treating and preventing cancer. Specific microbes or the microbial ecosystem can be modified via a multiplicity of processes, and therapeutic methods and approaches have been evolving. Microbial manipulation can be applied as an adjunct to traditional cancer therapies such as chemotherapy and immunotherapy. Furthermore, this approach displays great promise as a stand-alone therapy following the failure of standard therapy. Moreover, such strategies may also benefit patients by avoiding the emergence of toxic side effects that result in treatment discontinuation. A better understanding of the host-microbial ecosystem in patients with cancer, together with the development of methodologies for manipulating the microbiome, will help expand the frontiers of precision cancer therapeutics, thereby improving patient care. This review discusses the roles of the microbiota in oncogenesis and cancer therapy, with a focus on efforts to harness the microbiota to fight cancer.
Asunto(s)
Antineoplásicos/administración & dosificación , Microbioma Gastrointestinal , Inmunomodulación , Inmunoterapia/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Prebióticos/administración & dosificación , Animales , Interacciones Microbiota-Huesped , Humanos , Neoplasias/microbiología , Medicina de PrecisiónRESUMEN
Bacteria present in probiotics, particularly the common Lactobacillus and Bifidobacterium microbes, have been found to induce anti-cancer action by enhancing cancer cell apoptosis and protecting against oxidative stress. Probiotics supplements also decrease the cancer-producing microorganism Fusobacterium. Studies have demonstrated that gut microbiota modifies the effect of chemo/radiation therapy. Gut microbes not only enhance the action of chemotherapy drugs but also reduce the side effects of these medications. Additionally, gut microbes reduce immunotherapy toxicity, in particular, the presence of Bacteroidetes or Bifidobacterium decreases the development of colitis by ipilimumab therapy. Probiotics supplements containing Bifidobacterium also reduce chemotherapy-induced mucositis and radiation-induced diarrhea. This review focused on elucidating the mechanism behind the anti-cancer action of Bifidobacterium species. Available studies have revealed Bifidobacterium species decrease cancer cell proliferation via the inhibition of growth factor signaling as well as inducing mitochondrial-mediated apoptosis. Moreover, Bifidobacterium species reduce the adverse effects of chemo/immuno/radiation therapy by inhibiting proinflammatory cytokines. Further clinical studies are needed to identify the powerful and suitable Bifidobacterium strain for the development of adjuvant therapy to support chemo/immuno/radiation therapy.
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Antineoplásicos/uso terapéutico , Microbioma Gastrointestinal/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Probióticos/uso terapéutico , Antineoplásicos/efectos adversos , Bifidobacterium/efectos de los fármacos , Citocinas/genética , Suplementos Dietéticos/microbiología , Microbioma Gastrointestinal/genética , Humanos , Lactobacillus/efectos de los fármacos , Neoplasias/genética , Neoplasias/microbiología , Neoplasias/patologíaRESUMEN
Conventional anti-cancer therapy involves the use of chemical chemotherapeutics and radiation and are often non-specific in action. The development of drug resistance and the inability of the drug to penetrate the tumor cells has been a major pitfall in current treatment. This has led to the investigation of alternative anti-tumor therapeutics possessing greater specificity and efficacy. There is a significant interest in exploring the use of microbes as potential anti-cancer medicines. The inherent tropism of the bacteria for hypoxic tumor environment and its ability to be genetically engineered as a vector for gene and drug therapy has led to the development of bacteria as a potential weapon against cancer. In this review, we will introduce bacterial anti-cancer therapy with an emphasis on the various mechanisms involved in tumor targeting and tumor suppression. The bacteriotherapy approaches in conjunction with the conventional cancer therapy can be effective in designing novel cancer therapies. We focus on the current progress achieved in bacterial cancer therapies that show potential in advancing existing cancer treatment options and help attain positive clinical outcomes with minimal systemic side-effects.
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Bacterias/patogenicidad , Terapia Biológica/métodos , Neoplasias/terapia , Animales , Bacterias/metabolismo , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/toxicidad , Humanos , Neoplasias/microbiologíaRESUMEN
Consumption of green tea (GT) and GT polyphenols has prevented a range of cancers in rodents but has had mixed results in humans. Human subjects who drank GT for weeks showed changes in oral microbiome. However, GT-induced changes in RNA in oral epithelium were subject-specific, suggesting GT-induced changes of the oral epithelium occurred but differed across individuals. In contrast, studies in rodents consuming GT polyphenols revealed obvious changes in epithelial gene expression. GT polyphenols are poorly absorbed by digestive tract epithelium. Their metabolism by gut/oral microbial enzymes occurs and can alter absorption and function of these molecules and thus their bioactivity. This might explain the overall lack of consistency in oral epithelium RNA expression changes seen in human subjects who consumed GT. Each human has different gut/oral microbiomes, so they may have different levels of polyphenol-metabolizing bacteria. We speculate the similar gut/oral microbiomes in, for example, mice housed together are responsible for the minimal variance observed in tissue GT responses within a study. The consistency of the tissue response to GT within a rodent study eases the selection of a dose level that affects tumor rates. This leads to the theory that determination of optimal GT doses in a human requires knowledge about the gut/oral microbiome in that human.
Asunto(s)
Antioxidantes/uso terapéutico , Microbioma Gastrointestinal/efectos de los fármacos , Neoplasias/dietoterapia , Té/química , Animales , Antioxidantes/química , Humanos , Ratones , Boca/microbiología , Neoplasias/microbiología , Neoplasias/patología , Extractos Vegetales/química , Extractos Vegetales/uso terapéutico , Polifenoles/química , Polifenoles/uso terapéutico , Ratas , RoedoresRESUMEN
OBJECTIVE: This study determined the prevalence of Candida spp. in the saliva of cancer patients. Furthermore, we assessed the antimicrobial activity of mouthwashes against the isolated strains and its susceptibility to amphotericin B and fluconazole. METHODS: Thirty-four cancer patients undergoing radiotherapy, chemotherapy alone or combined treatment were investigated for oral Candida spp. colonization and compared in regard to mucositis presence. The maximum inhibitory dilution was used to assess the antimicrobial activity of Periogard®, Cepacol® Cool Ice and 0.12 % Chlorhexidine Digluconate mouthwashes against the isolates. In parallel, susceptibility to amphotericin B and fluconazole was determined by agar-based E-test. Data did not adhere to normal distribution as inferred by the Shapiro-Wilk test and statistical analysis was conducted by non-parametric McNemar test (α0.05). RESULTS: Twenty-seven participants (79.4 %) were male, 19 (55.9 %) had mucositis and 9 (26.5 %) were colonized by Candida spp. 12 different strains of Candida spp. were isolated, being Candida albicans the most prevalent strain. Risk of Candida spp. colonization was increased by almost twofold among the participants with mucositis (odds ratio: 1.84; 95 % confidence interval: 0.37-9.07). Mouthwash Cepacol® Cool Ice presented better antimicrobial activity against Candida spp. while 0.12 % Chlorhexidine exhibited the worst activity. All strains were sensitive to amphotericin B, and 2 non-albicans strains were dose-dependent sensitive to fluconazole. CONCLUSION: Considering the increased risk of colonization byCandida spp. in patients with mucositis, and the emergence of antifungal drug resistance, the antiseptics use could benefit the maintenance of cancer patient's oral health.
Asunto(s)
Antifúngicos/farmacología , Candida/efectos de los fármacos , Antisépticos Bucales/farmacología , Neoplasias/microbiología , Anfotericina B/farmacología , Farmacorresistencia Fúngica , Femenino , Fluconazol/farmacología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Prevalencia , Saliva/microbiologíaRESUMEN
Immune-checkpoint inhibitors (ICIs) have revolutionised the therapeutic landscape for multiple malignancies and the health of the gut microbiome (GM) is strongly linked with therapeutic responses to ICI. This review explores the implications of diet and medication on the GM for patients receiving ICI. Clinical trials are underway to explore the impact of factors such as faecal microbiota transfer, probiotics, prebiotics, bacteria consortia and a number of dietary interventions on patients receiving ICI. Randomised controlled trials are lacking, and inferences are currently based on short-term clinical and observational studies. Antibiotics should be avoided before ICI initiation, and depending on prospective data, future consideration may be given to temporary delay of initiation of non-urgent ICI if patient has had broad spectrum antibiotics within 1 month of planned treatment initiation. Proton pump inhibitor use should be discontinued when not clearly indicated and potential switch to a histamine H2-receptor antagonist considered. Patients should be advised to minimise animal meat intake and maximise plants, aiming to consume ≥30 plant types weekly. A high fibre intake (>30 g/day) has been seen to be beneficial in increasing the chance of ICI response. Fermented foods may have a beneficial effect on the GM and should be introduced where possible. Ideally, all patients should be referred to a nutritionist or dietician with knowledge of GM before commencing ICI.
Asunto(s)
Bacterias/efectos de los fármacos , Dieta , Microbioma Gastrointestinal/efectos de los fármacos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia , Neoplasias/tratamiento farmacológico , Animales , Antibacterianos/efectos adversos , Bacterias/inmunología , Dieta/efectos adversos , Suplementos Dietéticos , Disbiosis , Trasplante de Microbiota Fecal , Interacciones Huésped-Patógeno , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia/efectos adversos , Neoplasias/inmunología , Neoplasias/microbiología , Estado Nutricional , Inhibidores de la Bomba de Protones/efectos adversosRESUMEN
Cancer is the leading cause of deaths worldwide, though significant advances have occurred in its diagnosis and treatment. The development of resistance against chemotherapeutic agents, their side effects, and non-specific toxicity urge to screen for the novel anticancer agent. Hence, the development of novel anticancer agents with a new mechanism of action has become a major scientific challenge. Bacteria and bacterially produced bioactive compounds have recently emerged as a promising alternative for cancer therapeutics. Bacterial anticancer agents such as antibiotics, bacteriocins, non-ribosomal peptides, polyketides, toxins, etc. These are adopted different mechanisms of actions such as apoptosis, necrosis, reduced angiogenesis, inhibition of translation and splicing, and obstructing essential signaling pathways to kill cancer cells. Also, live tumor-targeting bacteria provided a unique therapeutic alternative for cancer treatment. This review summarizes the anticancer properties and mechanism of actions of the anticancer agents of bacterial origin and antitumor bacteria along with their possible future applications in cancer therapeutics.