RESUMO
OBJECTIVE: The aim of this study was to reveal certain features (anti-tumor/microbial activities) of postbiotics and heat-inactivated paraprobiotics obtained from two different bacteria with determined probiotic properties, which are thought to contribute to human health. METHODS: In the study, Lactobacillus reuteri ENA31 and L. rhamnosus GAA6 strains were used. Supernatants of postbiotically active cultures were used. Paraprobiotics were obtained by exposing probiotic bacteria to high temperatures. The cytotoxic effects of probiotics, paraprobiotics, and postbiotics were evaluated by the MTT method. IL-1/-10/-12/-13, TNF-α, IFN-γ, and neopterin parameters were determined via the ELISA method in immunity studies. RESULTS: It was detected that biotics had a cytotoxic effect on cancer cells with rising concentrations (paraprobioticAssuntos
Neoplasias Colorretais
, Lacticaseibacillus rhamnosus
, Probióticos
, Probióticos/farmacologia
, Probióticos/uso terapêutico
, Humanos
, Neoplasias Colorretais/imunologia
, Neoplasias Colorretais/microbiologia
, Limosilactobacillus reuteri
, Linhagem Celular Tumoral
, Citocinas
, Ensaio de Imunoadsorção Enzimática
, Neopterina
RESUMO
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 Escherichia coli (E. coli) and enterotoxigenic Bacteroides fragilis (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 Firmicute sand Bacteroidetes. Specific bacteria are also associated with the onset and progression of CRC, such as Fusobacterium nucleatum, E. coli, Enterococcus faecalis, Streptococcus gallolyticus, 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.
Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Bactérias , Bacteroides fragilis , Neoplasias Colorretais/microbiologia , Disbiose/complicações , Disbiose/microbiologia , Escherichia coli , Humanos , Inflamação/complicações , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/microbiologia , Qualidade de Vida , AreiaRESUMO
Colorectal cancer (CRC), also named as colon and rectal or bowel cancer, is one of the leading neoplasia diagnosed in the world. Genetic sequencing studies of microorganisms from the intestinal microbiota of patients with CRC revealed that changes in its composition occur with the development of the disease, which can play a fundamental role in its development, being mediated by the production of metabolites and toxins that damage enterocytes. Some microorganisms are frequently reported in the literature as the main agents of this process, such as the bacteria Fusobacterium nucleatum, Escherichia coli and Bacteroides fragilis. Thus, understanding the mechanisms and function of each microorganism in CRC is essential for the development of treatment tools that focus on the gut microbiota. This review verifies current research aimed at evaluating the microorganisms present in the microbiota that can influence the development of CRC, as well as possible forms of treatment that can prevent the initiation and/or spread of this disease. Due to the incidence of CRC, alternatives have been launched considering factors beyond those already known in the disease development, such as diet, fecal microbiota transplantation, use of probiotics and antibiotics, which have been widely studied for this purpose. However, despite being promising, the studies that focus on the development of new therapeutic approaches targeting the microorganisms that cause CRC still need to be improved and better developed, involving new techniques to elucidate the effectiveness and safety of these new methods.
Assuntos
Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/terapia , Microbioma Gastrointestinal/fisiologia , Neoplasias Colorretais/prevenção & controle , Transplante de Microbiota Fecal , Humanos , Microbiota , Probióticos/uso terapêuticoRESUMO
Colorectal cancer (CRC) is one of the most frequent and deadly neoplasms worldwide. Genetic factors, lifestyle habits, and inflammation are important risk factors associated with CRC development. In recent years, growing evidence has supporting the significant role of the intestinal microbiome in CRC carcinogenesis. Disturbances in the healthy microbial balance, known as dysbiosis, are frequently observed in these patients. Pathogenic microorganisms that induce intestinal dysbiosis have become an important target to determine the role of bacterial infection in tumorigenesis. Interestingly, the presence of different bacterial strains, such as Fusobacterium nucleatum, has been detected in tissue and stool from patients with CRC and associated with substantial clinical and molecular features, as well as with patient therapy response. Therefore, understanding how the presence and levels of F. nucleatumstrains in the gut affect the risk of CRC onset and progression may inform suitable candidates for interventions focused on modulation of this bacteria. Here we review new insights into the role of gut microbiota in CRC carcinogenesis and the clinical utility of using the detection of F. nucleatum in different settings such as screening, prognosis, and microbiota modulation as a means to prevent cancer, augment therapies, and reduce adverse effects of treatment.
Assuntos
Carcinogênese , Neoplasias Colorretais/microbiologia , Fusobacterium nucleatum/patogenicidade , Intestinos/patologia , Animais , Transformação Celular Neoplásica , Progressão da Doença , Disbiose , Microbioma Gastrointestinal , Humanos , Intestinos/microbiologia , Camundongos , Fatores de RiscoRESUMO
Se estima que aproximadamente 100 trillones de microorganismos (incluidos bacterias, virus y hongos) residen en el intestino humano adulto y que el total del material genético del microbioma es 100 veces superior al del genoma humano. Esta comunidad, conocida como microbioma se adquiere al momento del nacimiento a través de la flora comensal de la piel, vagina y heces de la madre y se mantiene relativamente estable a partir de los dos años desempeñando un papel crítico tanto en el estado de salud como en la enfermedad. El desarrollo de nuevas tecnologías, como los secuenciadores de próxima generación (NGS), permiten actualmente realizar un estudio mucho más preciso de ella que en décadas pasadas cuando se limitaba a su cultivo. Si bien esto ha llevado a un crecimiento exponencial en las publicaciones, los datos sobre las poblaciones Latinoamérica son casi inexistentes. La investigación traslacional en microbioma (InTraMic) es una de las líneas que se desarrollan en el Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB). Esta se inició en 2018 con la línea de cáncer colorrectal (CCR) en una colaboración con el Colorectal Cancer Research Group del Leeds Institute of Medical Research en el proyecto Large bowel microbiome disease network: Creation of a proof of principle exemplar in colorectal cancer across three continents. A fines de 2019 se cumplió el objetivo de comprobar la factibilidad de la recolección, envío y análisis de muestras de MBF en 5 continentes, incluyendo muestras provenientes de la Argentina, Chile, India y Vietnam. Luego de haber participado de capacitaciones en Inglaterra, se ha cumplido con el objetivo de la etapa piloto, logrando efectivizar la recolección, envío y análisis metagenómico a partir de la secuenciación de la región V4 del ARNr 16S. En 2019, la línea de enfermedad de hígado graso no alcohólico se sumó a la InTraMic iniciando una caracterización piloto en el marco de una colaboración con el laboratorio Novartis. Los resultados de ese estudio, así como el de cáncer colorrectal, están siendo enviados a publicación. En 2020, con la incorporación de la línea de trasplante alogénico de células progenitoras hematopoyéticas, fue presentado un proyecto para un subsidio del CONICET que ha superado la primera etapa de evaluación. En el presente artículo se brinda una actualización sobre la caracterización taxonómica de microbioma y se describen las líneas de investigación en curso. (AU)
It is estimated that approximately 100 trillion microorganisms (including bacteria, viruses, and fungi) reside in the adult human intestine, and that the total genetic material of the microbiome is 100 times greater than that of the human genome. This community, known as the microbiome, is acquired at birth through the commensal flora of the mother's skin, vagina, and feces and remains relatively stable after two years, playing a critical role in both the state of health and in disease. The development of new technologies, such as next-generation sequencers (NGS), currently allow for a much more precise study of it than in past decades when it was limited to cultivation. Although this has led to exponential growth in publications, data on Latin American populations is almost non-existent. Translational research in microbiome (InTraMic) is one of the lines developed at the Instituto de Medicina Traslacional e Ingeniería Biomédica (IMTIB). This started in 2018 with the Colorectal Cancer Line (CRC) in a collaboration with the Colorectal Cancer Research Group of the Leeds Institute of Medical Research in the project "Large bowel microbiome disease network: Creation of a proof of principle exemplar in colorectal cancer across three continents". At the end of 2019, the objective of verifying the feasibility of collecting, sending and analyzing MBF samples on 5 continents, including samples from Argentina, Chile, India and Vietnam, was met. After having participated in training in England, the objective of the pilot stage has been met, achieving the collection, delivery and metagenomic analysis from the sequencing of the V4 region of the 16S rRNA. In 2019, the non-alcoholic fatty liver disease line joined InTraMic, initiating a pilot characterization in the framework of a collaboration with the Novartis laboratory. The results of that study, as well as that of colorectal cancer, are being published. In 2020, with the incorporation of the allogeneic hematopoietic stem cell transplantation line, a project was presented for a grant from the CONICET that has passed the first stage of evaluation. This article provides an update on the taxonomic characterization of the microbiome and describes the lines of ongoing research. (AU)
Assuntos
Humanos , Pesquisa Translacional Biomédica/organização & administração , Microbioma Gastrointestinal/genética , Transplante Homólogo , Vietnã , Aztreonam/uso terapêutico , RNA Ribossômico 16S/análise , Neoplasias Colorretais/genética , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/epidemiologia , Classificação/métodos , Transplante de Células-Tronco Hematopoéticas , Metagenômica , Pesquisa Translacional Biomédica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/tendências , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Microbioma Gastrointestinal/fisiologia , Índia , América Latina , Sangue OcultoRESUMO
Tools that predict the risk of colorectal cancer are important for early diagnosis, given the high mortality rate for this cancer. The composition of the intestinal microbiota is now considered to be a risk factor for the development of colorectal cancer. This discovery has motivated a growing number of studies to identify the micro-organisms responsible for the onset and/or progression of colorectal cancer. With this in mind, this review discusses the relationship between the composition of the intestinal microbiota and colorectal cancer risk. Prospective and case-control studies indicate that the intestinal microbiota of individuals with colorectal cancer usually contains a greater proportion of bacteria responsible for gastrointestinal tract inflammatory diseases, as well as bacteria that produce toxins and carcinogenic metabolites. In contrast, there tends to be a reduced presence of butyric acid-producing bacteria, probiotic bacteria and potentially probiotic bacteria. Despite these differences, the onset and development of colorectal cancer cannot be attributed to a specific micro-organism. Thus, studies focused on the formation of the intestinal microbiota and factors that modulate its composition are important for the development of approaches for colorectal cancer prevention.
Assuntos
Neoplasias Colorretais/microbiologia , Microbioma Gastrointestinal , Intestinos/microbiologia , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Microambiente Celular , Neoplasias Colorretais/fisiopatologia , HumanosRESUMO
BACKGROUND: Colorectal cancer is one of the most commonly diagnosed cancers around the world. One of the factors involved in the development of colorectal cancer is the changes in the normal flora of the intestine. OBJECTIVE: In this study, the mean copy number of Enterococcus faecalis in people with polyps and people with colorectal cancer has been evaluated in comparison with healthy controls. METHODS: In this study, 25 patients with colorectal cancer and 28 patients with intestinal polyps were selected and stool specimens were taken. In addition, 24 healthy individuals were selected as control group. Extraction of bacterial DNA from the stool sample were performed. The molecular methods of PCR for confirmation of standard strain and absolute Real Time PCR (qRT-PCR) method were used to evaluate the number of Enterococcus faecalis in the studied groups. RESULTS: The results of this study indicate that the mean copy number of Enterococcus faecalis in patients with colorectal cancer was 11.2x109 per gram of stool, and in patients with polyps was 9.4x108 per gram of stool. In healthy people, this number was 9x108 per gram of stool. There was a significant difference between the implicit copy numbers in the three groups. (P<0.05). CONCLUSION: Enterococcus faecalis in faecal flora of people with colorectal cancer was significantly higher than those with polyps and healthy people. This could potentially signify the ability of this bacterium to induce colorectal cancer. More studies are needed to prove this theory.
Assuntos
Pólipos do Colo/microbiologia , Neoplasias Colorretais/microbiologia , Enterococcus faecalis/isolamento & purificação , Fezes/microbiologia , Idoso , Estudos de Casos e Controles , DNA Bacteriano/análise , Enterococcus faecalis/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo RealRESUMO
ABSTRACT BACKGROUND: Colorectal cancer is one of the most commonly diagnosed cancers around the world. One of the factors involved in the development of colorectal cancer is the changes in the normal flora of the intestine. OBJECTIVE: In this study, the mean copy number of Enterococcus faecalis in people with polyps and people with colorectal cancer has been evaluated in comparison with healthy controls. METHODS: In this study, 25 patients with colorectal cancer and 28 patients with intestinal polyps were selected and stool specimens were taken. In addition, 24 healthy individuals were selected as control group. Extraction of bacterial DNA from the stool sample were performed. The molecular methods of PCR for confirmation of standard strain and absolute Real Time PCR (qRT-PCR) method were used to evaluate the number of Enterococcus faecalis in the studied groups. RESULTS: The results of this study indicate that the mean copy number of Enterococcus faecalis in patients with colorectal cancer was 11.2x109 per gram of stool, and in patients with polyps was 9.4x108 per gram of stool. In healthy people, this number was 9x108 per gram of stool. There was a significant difference between the implicit copy numbers in the three groups. (P<0.05). CONCLUSION: Enterococcus faecalis in faecal flora of people with colorectal cancer was significantly higher than those with polyps and healthy people. This could potentially signify the ability of this bacterium to induce colorectal cancer. More studies are needed to prove this theory.
RESUMO CONTEXTO: O câncer colorretal é um dos cânceres mais comumente diagnosticados em todo o mundo. Um dos fatores envolvidos no desenvolvimento do câncer colorretal é a mudança na flora normal do intestino. OBJETIVO: O número médio de cópias de Enterococcus faecalis em pessoas com pólipos e pessoas com câncer colorretal foram avaliados em comparação com controles saudáveis. MÉTODOS: Neste estudo, 25 pacientes com câncer colorretal e 28 pacientes com pólipos intestinais foram selecionados e amostras de fezes foram adquiridas. Além disso, 24 indivíduos saudáveis foram selecionados como grupo controle. A extração do DNA bacteriano da amostra coletada foi executada. Os métodos moleculares de PCR para confirmação da cepa padrão e o método absoluto de PCR em tempo real (qRT-PCR) foram utilizados para avaliar o número de Enterococcus faecalis nos grupos estudados. RESULTADOS: Os resultados deste estudo indicam que o número médio de cópias de Enterococcus faecalis em pacientes com câncer colorretal foi de 11,2x109 por grama de fezes, e em pacientes com pólipos foi de 9,4x108 por grama de fezes. Em pessoas saudáveis, este número foi de 9x108 por grama de fezes. Houve diferença significativa entre os números de cópia implícita nos três grupos. (P<0,05). CONCLUSÃO: Enterococcus faecalis na flora fecal de pessoas com câncer colorretal foi significativamente maior do que aqueles com pólipos e pessoas saudáveis. Isto poderia potencialmente significar a capacidade desta bactéria para induzir o câncer colorretal. Mais estudos são necessários para provar esta teoria.
Assuntos
Humanos , Masculino , Feminino , Idoso , Neoplasias Colorretais/microbiologia , Pólipos do Colo/microbiologia , Enterococcus faecalis/isolamento & purificação , Fezes/microbiologia , DNA Bacteriano/análise , Estudos de Casos e Controles , Enterococcus faecalis/genética , Reação em Cadeia da Polimerase em Tempo Real , Pessoa de Meia-IdadeRESUMO
ABSTRACT BACKGROUND: Colorectal cancer is one of the major causes of death worldwide. Many studies have been done on the biology of its formation as well as its treatment in recent years. One of the factors involved in the formation or treatment of this malignancy can be attributed to the microbial flora in the intestine. OBJECTIVE: This study investigate the potential preventive effect of Lactobacillus acidophilus and Lactobacillus plantarum in patients with polyps or colorectal cancer (CRC). METHODS: A total of 77 samples were selected in the form of three groups including individuals suffering from CRC, polyps and healthy subjects. Genomic DNA of fecal specimens and standard strains were extracted and amplified employing primers targeting of the 16S rRNA gene for initial detection. Absolute Real Time PCR quantification was used to determine the copy of the bacterial expression per gram of feces. RESULTS: No significant difference were observed between age and gender in the mentioned groups (P=0.06). The average copy number of Lactobacillus acidophilus shows Significant difference between the healthy group and those with polyps (P<0.0001), the healthy group and those with colorectal cancer (P<0.0001), as well as those with polyps and the colorectal cancer patients (P<0.0001). CONCLUSION: These results may indicate that taking Lactobacillus acidophilus in people with a family history of CRC and people with polyps may be a way of preventing, treating or reducing the severity of CRC.
RESUMO CONTEXTO: O câncer colorretal é uma das principais causas de morte em todo o mundo. Muitos estudos têm sido feitos sobre a biologia de sua formação, bem como o seu tratamento nos últimos anos. Um dos fatores envolvidos na formação ou no tratamento desta malignidade pode ser atribuído à flora microbiana no intestino. OBJETIVO: Este estudo investigou o potencial efeito preventivo de Lactobacillus acidophilus e Lactobacillus plantarum em pacientes com pólipos ou câncer colorretal (CCR). MÉTODOS: Um total de 77 amostras foram selecionadas e três grupos foram formados, a saber, indivíduos portadores de CCR, pólipos e indivíduos saudáveis. O DNA genomico de espécimes fecais e de amostras padrão foi extraído e amplificado empregando primers que focalizaram o gene do rRNA 16S para a deteção inicial. A quantificação do PCR em tempo real absoluto foi utilizada para determinar a cópia da expressão bacteriana por grama de fezes. RESULTADOS: Não foram observadas diferenças significativas entre idade e sexo nos grupos citados (P=0,06). O número médio de cópias de Lactobacillus acidophilus mostra diferença significativa entre o grupo saudável e aqueles com pólipos (P<0,0001), o grupo saudável e aqueles com câncer colorretal (P<0,0001), bem como aqueles com pólipos e câncer colorretal pacientes (P<0,0001). CONCLUSÃO: Estes resultados podem indicar que a ingestão de Lactobacillus acidophilus em pessoas com antecedentes familiares de CCR e pessoas com pólipos pode ser uma forma de prevenir, tratar ou reduzir a gravidade da CCR.
Assuntos
Humanos , Masculino , Feminino , Idoso , Neoplasias Colorretais/microbiologia , Pólipos do Colo/microbiologia , Lactobacillus plantarum/isolamento & purificação , Fezes/microbiologia , Lactobacillus acidophilus/isolamento & purificação , DNA Bacteriano/análise , Neoplasias Colorretais/prevenção & controle , Pólipos do Colo/prevenção & controle , Reação em Cadeia da Polimerase , Lactobacillus plantarum/genética , Lactobacillus acidophilus/genética , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Colorectal cancer is one of the major causes of death worldwide. Many studies have been done on the biology of its formation as well as its treatment in recent years. One of the factors involved in the formation or treatment of this malignancy can be attributed to the microbial flora in the intestine. OBJECTIVE: This study investigate the potential preventive effect of Lactobacillus acidophilus and Lactobacillus plantarum in patients with polyps or colorectal cancer (CRC). METHODS: A total of 77 samples were selected in the form of three groups including individuals suffering from CRC, polyps and healthy subjects. Genomic DNA of fecal specimens and standard strains were extracted and amplified employing primers targeting of the 16S rRNA gene for initial detection. Absolute Real Time PCR quantification was used to determine the copy of the bacterial expression per gram of feces. RESULTS: No significant difference were observed between age and gender in the mentioned groups (P=0.06). The average copy number of Lactobacillus acidophilus shows Significant difference between the healthy group and those with polyps (P<0.0001), the healthy group and those with colorectal cancer (P<0.0001), as well as those with polyps and the colorectal cancer patients (P<0.0001). CONCLUSION: These results may indicate that taking Lactobacillus acidophilus in people with a family history of CRC and people with polyps may be a way of preventing, treating or reducing the severity of CRC.