Impacto do uso de simbióticos na microbiota intestinal de pacientes com neoplasia colorretal submetidos a tratamento cirúrgico: ensaio clínico randomizado.

Detalhes bibliográficos
Autor(a) principal: Luísa Martins Trindade
Data de Publicação: 2023
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UFMG
Texto Completo: http://hdl.handle.net/1843/59524
Resumo: Surgery is often used to treat colorectal cancer (CRC). Patients undergoing major operations, such as intestinal resections, demonstrate an increased risk for the development of intestinal dysbiosis. The administration of biotherapeutic agents, such as the symbiotic, can maintain intestinal homeostasis, modulate the immune system, and, consequently, reduce the risk of complications. Thus, the present study aimed to evaluate the impact of preoperative symbiotic supplementation on the intestinal microbiota of patients with colorectal cancer undergoing surgical treatment. Methods: This is a unicentric parallel triple masked randomized clinical trial, carried out at the Hospital das Clínicas of the Federal University of Minas Gerais. The study included patients diagnosed with CRC, candidates for tumor resection surgery, of both sexes, aged ≥ 18 years, who agreed to participate and signed the Informed Consent Form. The study was approved by the Research Ethics Committee of the Federal University of Minas Gerais (CEP/UFMG), under process number CAAE 24375713.0.0000.5149 and registered in Clinical Trials under number NCT04874883. Patients were randomized to receive supplementation with symbiotic or maltodextrin (control), twice a day, for a minimum of four and a maximum of ten days. The patients allocated in the treatment group received the symbiotic Simbioflora® (commercial preparation containing 5.5g of fructooligosaccharides (FOS) added with four species of probiotic (Lactobacillus paracasei LPC-31; Lactobacillus rhamnosus HN001; Lactobacillus acidophilus NCFM; Bifidobacterium lactis HN019, at a concentration of 109 CFU per strain), while the patients in the control group received 6 grams of maltodextrin. In the pre- and postoperative periods, all patients underwent nutritional, anthropometric, food consumption, bowel function and complaints assessment. during hospitalization until discharge to investigate complications. In addition, feces were collected, before treatment (T1) and operation (T2) and, at hospital discharge (T3), to assess the intestinal microbiota and fatty acids of short chain (AGCC) During the operation, fragments of normal (TN) and tumor (TT) tissue were collected for evaluation of cytokine expression, mucus production and proliferation of the tumor marker Ki67. Statistical analyzes were performed using (Statistical Package for the Social Sciences for Windows Student) SPSS and PRISMA programs. The significance level adopted was 5%. Results: In all, 46 patients completed the study, 23 in the symbiotic group and 23 in the control group. Statistical similarity was identified between the groups, in the pre- and postoperative periods, in relation to general and clinical characteristics, as well as nutritional, anthropometric and food consumption status (p>0.05), except for protein consumption, which was higher in the symbiotic group at baseline (p<0.05). No statistical differences were identified between the two groups regarding the first evacuation, flatus elimination, digestive complaints, length of stay, postoperative complications and in-hospital mortality (p>0.05). However, the analysis of the intestinal microbiota of the feces collected in T2 showed a significant increase in the Firmicutes phylum, the Bacillaceae family and the Blautia genus after symbiotic supplementation compared to the control group (p<0.05). In addition, symbiotic supplementation contributed to the modulation of the intestinal microbiota of patients who did not have infectious complications (p<0.05). An increase in the Lachnospiraceae family and in the Faecalibacterium, Lachnospira, Clostridium, Bilophila, Slakia and Selenomomonas genera at T2 was identified in these patients (p<0.05). Greater production of butyrate in T2 and T3, and of acetate and propionate in T2, were demonstrated in the symbiotic group, compared to the control group (p<0.05). No significant differences were identified between groups in cytokine expression, TN mucus production and Ki67 expression (p>0.05). However, increased mucus production in TT was identified in the symbiotic group, compared with the control (p>0.05), as well as increased expression of Ki67 in the TN of both groups (p>0.05). Conclusion: The results of the present study demonstrated that preoperative symbiotic supplementation of patients with RCC undergoing tumor resection was able to modulate the intestinal microbiota, the production of SCFA and mucus, however, without repercussions on clinical outcomes.
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spelling Impacto do uso de simbióticos na microbiota intestinal de pacientes com neoplasia colorretal submetidos a tratamento cirúrgico: ensaio clínico randomizado.Câncer colorretalSimbióticoComplicações pós operatóriasMicrobiota intestinalAGCCKi67Surgery is often used to treat colorectal cancer (CRC). Patients undergoing major operations, such as intestinal resections, demonstrate an increased risk for the development of intestinal dysbiosis. The administration of biotherapeutic agents, such as the symbiotic, can maintain intestinal homeostasis, modulate the immune system, and, consequently, reduce the risk of complications. Thus, the present study aimed to evaluate the impact of preoperative symbiotic supplementation on the intestinal microbiota of patients with colorectal cancer undergoing surgical treatment. Methods: This is a unicentric parallel triple masked randomized clinical trial, carried out at the Hospital das Clínicas of the Federal University of Minas Gerais. The study included patients diagnosed with CRC, candidates for tumor resection surgery, of both sexes, aged ≥ 18 years, who agreed to participate and signed the Informed Consent Form. The study was approved by the Research Ethics Committee of the Federal University of Minas Gerais (CEP/UFMG), under process number CAAE 24375713.0.0000.5149 and registered in Clinical Trials under number NCT04874883. Patients were randomized to receive supplementation with symbiotic or maltodextrin (control), twice a day, for a minimum of four and a maximum of ten days. The patients allocated in the treatment group received the symbiotic Simbioflora® (commercial preparation containing 5.5g of fructooligosaccharides (FOS) added with four species of probiotic (Lactobacillus paracasei LPC-31; Lactobacillus rhamnosus HN001; Lactobacillus acidophilus NCFM; Bifidobacterium lactis HN019, at a concentration of 109 CFU per strain), while the patients in the control group received 6 grams of maltodextrin. In the pre- and postoperative periods, all patients underwent nutritional, anthropometric, food consumption, bowel function and complaints assessment. during hospitalization until discharge to investigate complications. In addition, feces were collected, before treatment (T1) and operation (T2) and, at hospital discharge (T3), to assess the intestinal microbiota and fatty acids of short chain (AGCC) During the operation, fragments of normal (TN) and tumor (TT) tissue were collected for evaluation of cytokine expression, mucus production and proliferation of the tumor marker Ki67. Statistical analyzes were performed using (Statistical Package for the Social Sciences for Windows Student) SPSS and PRISMA programs. The significance level adopted was 5%. Results: In all, 46 patients completed the study, 23 in the symbiotic group and 23 in the control group. Statistical similarity was identified between the groups, in the pre- and postoperative periods, in relation to general and clinical characteristics, as well as nutritional, anthropometric and food consumption status (p>0.05), except for protein consumption, which was higher in the symbiotic group at baseline (p<0.05). No statistical differences were identified between the two groups regarding the first evacuation, flatus elimination, digestive complaints, length of stay, postoperative complications and in-hospital mortality (p>0.05). However, the analysis of the intestinal microbiota of the feces collected in T2 showed a significant increase in the Firmicutes phylum, the Bacillaceae family and the Blautia genus after symbiotic supplementation compared to the control group (p<0.05). In addition, symbiotic supplementation contributed to the modulation of the intestinal microbiota of patients who did not have infectious complications (p<0.05). An increase in the Lachnospiraceae family and in the Faecalibacterium, Lachnospira, Clostridium, Bilophila, Slakia and Selenomomonas genera at T2 was identified in these patients (p<0.05). Greater production of butyrate in T2 and T3, and of acetate and propionate in T2, were demonstrated in the symbiotic group, compared to the control group (p<0.05). No significant differences were identified between groups in cytokine expression, TN mucus production and Ki67 expression (p>0.05). However, increased mucus production in TT was identified in the symbiotic group, compared with the control (p>0.05), as well as increased expression of Ki67 in the TN of both groups (p>0.05). Conclusion: The results of the present study demonstrated that preoperative symbiotic supplementation of patients with RCC undergoing tumor resection was able to modulate the intestinal microbiota, the production of SCFA and mucus, however, without repercussions on clinical outcomes.O ato operatório é frequentemente empregado para tratamento do câncer colorretal (CCR). Pacientes submetidos a operações de grande porte, como nas ressecções intestinais, demonstram risco aumentado para o desenvolvimento de disbiose intestinal. A administração de agentes bioterapêuticos, como o simbiótico, pode manter a homeostase intestinal, modular o sistema imunológico, e, consequentemente, reduzir o risco de complicações. Assim, o presente trabalho teve por objetivo avaliar o impacto da suplementação pré-operatória com simbiótico na microbiota intestinal de pacientes com neoplasia colorretal submetidos a tratamento cirúrgico. Métodos: Trata-se de ensaio clínico randomizado triplo mascarado paralelo unicêntrico, realizado no Hospital das Clínicas da Universidade Federal de Minas Gerais. Foram incluídos no estudo, pacientes diagnosticados com CCR, candidatos à operação para ressecção tumoral, de ambos os sexos, com idade ≥ 18 anos, que aceitaram participar e assinaram o Termo de Consentimento Livre e Esclarecido. O estudo teve a aprovação do Comitê de Ética em Pesquisa da Universidade Federal de Minas Gerais (CEP/ UFMG), sob o número do processo CAAE 24375713.0.0000.5149 e registrado no Clinical Trials sob o número NCT04874883. Os pacientes foram randomizados para receber suplementação com simbiótico ou maltodextrina (controle), duas vezes ao dia, por no mínimo quatro e máximo dez dias. Os pacientes que foram alocados no grupo tratamento receberam o simbiótico Simbioflora® (preparação comercial contendo 5,5g de frutooligossacarídeo (FOS) adicionados com quatro espécies de probiótico (Lactobacillus paracasei LPC31; Lactobacillus rhamnosus HN001; Lactobacillus acidophilus NCFM; Bifidobacterium lactis HN019, na concentração de 109 UFC por cepa), enquanto que, os pacientes do grupo controle receberam 6 gramas de maltodextrina. Nos períodos pré e pós-operatórios todos os pacientes foram submetidos à avaliação nutricional, antropométrica, consumo alimentar, funcionamento intestinal e queixas. Os indivíduos foram acompanhados durante a internação até a alta para investigação das complicações. Além disso, fezes foram coletadas, antes do tratamento (T1) e da operação (T2) e, no momento da alta hospitalar (T3), para avaliação da microbiota intestinal e ácidos graxos de cadeia curta (AGCC). Durante a operação, fragmentos do tecido normal (TN) e tumoral (TT) foram coletados para avaliação da expressão de citocinas, produção de muco e proliferação do marcador tumoral Ki67. As análises estatísticas foram realizadas nos programas (Statistical Package for the Social Sciences for Windows Student) SPSS e PRISMA. O nível de significância adotado foi de 5%. Resultados: Ao todo, 46 pacientes finalizaram o estudo, sendo 23 no grupo simbiótico e 23 no grupo controle. Semelhança estatística foi identificada entre os grupos, nos períodos pré e pós- operatórios, em relação as características gerais e clínicas, bem como estado nutricional, antropométrico e do consumo alimentar (p>0,05), exceto para o consumo proteico, que foi maior no grupo simbiótico no início do estudo (p<0,05). Não foram identificadas diferenças estatísticas, entre os dois grupos, na primeira evacuação, na eliminação de flatos, nas queixas digestivas, no tempo de internação, na complicações pós-operatórias e na mortalidade intrahospitalar (p>0,05). Contudo, a análise da microbiota intestinal das fezes coletadas no T2 demonstrou aumento significativo do filo Firmicutes, da família Bacillaceae e do gênero Blautia após a suplementação de simbiótico comparado ao grupo controle (p<0,05). Além disso, a suplementação com simbiótico contribuiu para a modulação da microbiota intestinal dos pacientes que não apresentaram complicações infecciosas (p<0,05). Aumento da família Lachnospiraceae e dos gêneros Faecalibacterium, Lachnospira, Clostridium, Bilophila, Slakia e Selenomomonas, no T2, foram identificadas nesses pacientes (p<0,05). Maior produção de butirato no T2 e T3 e, de acetato e propionato no T2, foram demonstradas no grupo simbiótico, comparado ao grupo controle (p<0,05). Não foram identificadas diferenças significativas, entre os grupos, na expressão de citocinas, produção de muco no TN e expressão de Ki67 (p>0,05). Entretanto, aumento da produção de muco no TT foi identificado no grupo simbiótico, comparado com o controle (p>0,05), assim como aumento da expressão de Ki67 no TN de ambos os grupos (p>0,05). Conclusão: Os resultados do presente trabalho demonstraram que a suplementação com simbiótico, no pré-operatório, dos pacientes com CCR submetidos à ressecção tumoral foi capaz de modular a microbiota intestinal, a produção de AGCC e de muco, porém, sem repercussões nos desfechos clínicos.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorUniversidade Federal de Minas GeraisBrasilFARMACIA - FACULDADE DE FARMACIAPrograma de Pós-Graduação em Ciência de AlimentosUFMGSimone de Vasconcelos Generosohttp://lattes.cnpq.br/5553688290821141Rodrigo Gomes da SilvaEnio FerreiraSilvia Fernandes MauricioMaria Isabel Toulson Davisson CorreiaEliane Lopes RosadoLuísa Martins Trindade2023-10-17T13:41:11Z2023-10-17T13:41:11Z2023-05-29info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://hdl.handle.net/1843/59524porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMG2023-10-17T13:41:11Zoai:repositorio.ufmg.br:1843/59524Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oairepositorio@ufmg.bropendoar:2023-10-17T13:41:11Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
dc.title.none.fl_str_mv Impacto do uso de simbióticos na microbiota intestinal de pacientes com neoplasia colorretal submetidos a tratamento cirúrgico: ensaio clínico randomizado.
title Impacto do uso de simbióticos na microbiota intestinal de pacientes com neoplasia colorretal submetidos a tratamento cirúrgico: ensaio clínico randomizado.
spellingShingle Impacto do uso de simbióticos na microbiota intestinal de pacientes com neoplasia colorretal submetidos a tratamento cirúrgico: ensaio clínico randomizado.
Luísa Martins Trindade
Câncer colorretal
Simbiótico
Complicações pós operatórias
Microbiota intestinal
AGCC
Ki67
title_short Impacto do uso de simbióticos na microbiota intestinal de pacientes com neoplasia colorretal submetidos a tratamento cirúrgico: ensaio clínico randomizado.
title_full Impacto do uso de simbióticos na microbiota intestinal de pacientes com neoplasia colorretal submetidos a tratamento cirúrgico: ensaio clínico randomizado.
title_fullStr Impacto do uso de simbióticos na microbiota intestinal de pacientes com neoplasia colorretal submetidos a tratamento cirúrgico: ensaio clínico randomizado.
title_full_unstemmed Impacto do uso de simbióticos na microbiota intestinal de pacientes com neoplasia colorretal submetidos a tratamento cirúrgico: ensaio clínico randomizado.
title_sort Impacto do uso de simbióticos na microbiota intestinal de pacientes com neoplasia colorretal submetidos a tratamento cirúrgico: ensaio clínico randomizado.
author Luísa Martins Trindade
author_facet Luísa Martins Trindade
author_role author
dc.contributor.none.fl_str_mv Simone de Vasconcelos Generoso
http://lattes.cnpq.br/5553688290821141
Rodrigo Gomes da Silva
Enio Ferreira
Silvia Fernandes Mauricio
Maria Isabel Toulson Davisson Correia
Eliane Lopes Rosado
dc.contributor.author.fl_str_mv Luísa Martins Trindade
dc.subject.por.fl_str_mv Câncer colorretal
Simbiótico
Complicações pós operatórias
Microbiota intestinal
AGCC
Ki67
topic Câncer colorretal
Simbiótico
Complicações pós operatórias
Microbiota intestinal
AGCC
Ki67
description Surgery is often used to treat colorectal cancer (CRC). Patients undergoing major operations, such as intestinal resections, demonstrate an increased risk for the development of intestinal dysbiosis. The administration of biotherapeutic agents, such as the symbiotic, can maintain intestinal homeostasis, modulate the immune system, and, consequently, reduce the risk of complications. Thus, the present study aimed to evaluate the impact of preoperative symbiotic supplementation on the intestinal microbiota of patients with colorectal cancer undergoing surgical treatment. Methods: This is a unicentric parallel triple masked randomized clinical trial, carried out at the Hospital das Clínicas of the Federal University of Minas Gerais. The study included patients diagnosed with CRC, candidates for tumor resection surgery, of both sexes, aged ≥ 18 years, who agreed to participate and signed the Informed Consent Form. The study was approved by the Research Ethics Committee of the Federal University of Minas Gerais (CEP/UFMG), under process number CAAE 24375713.0.0000.5149 and registered in Clinical Trials under number NCT04874883. Patients were randomized to receive supplementation with symbiotic or maltodextrin (control), twice a day, for a minimum of four and a maximum of ten days. The patients allocated in the treatment group received the symbiotic Simbioflora® (commercial preparation containing 5.5g of fructooligosaccharides (FOS) added with four species of probiotic (Lactobacillus paracasei LPC-31; Lactobacillus rhamnosus HN001; Lactobacillus acidophilus NCFM; Bifidobacterium lactis HN019, at a concentration of 109 CFU per strain), while the patients in the control group received 6 grams of maltodextrin. In the pre- and postoperative periods, all patients underwent nutritional, anthropometric, food consumption, bowel function and complaints assessment. during hospitalization until discharge to investigate complications. In addition, feces were collected, before treatment (T1) and operation (T2) and, at hospital discharge (T3), to assess the intestinal microbiota and fatty acids of short chain (AGCC) During the operation, fragments of normal (TN) and tumor (TT) tissue were collected for evaluation of cytokine expression, mucus production and proliferation of the tumor marker Ki67. Statistical analyzes were performed using (Statistical Package for the Social Sciences for Windows Student) SPSS and PRISMA programs. The significance level adopted was 5%. Results: In all, 46 patients completed the study, 23 in the symbiotic group and 23 in the control group. Statistical similarity was identified between the groups, in the pre- and postoperative periods, in relation to general and clinical characteristics, as well as nutritional, anthropometric and food consumption status (p>0.05), except for protein consumption, which was higher in the symbiotic group at baseline (p<0.05). No statistical differences were identified between the two groups regarding the first evacuation, flatus elimination, digestive complaints, length of stay, postoperative complications and in-hospital mortality (p>0.05). However, the analysis of the intestinal microbiota of the feces collected in T2 showed a significant increase in the Firmicutes phylum, the Bacillaceae family and the Blautia genus after symbiotic supplementation compared to the control group (p<0.05). In addition, symbiotic supplementation contributed to the modulation of the intestinal microbiota of patients who did not have infectious complications (p<0.05). An increase in the Lachnospiraceae family and in the Faecalibacterium, Lachnospira, Clostridium, Bilophila, Slakia and Selenomomonas genera at T2 was identified in these patients (p<0.05). Greater production of butyrate in T2 and T3, and of acetate and propionate in T2, were demonstrated in the symbiotic group, compared to the control group (p<0.05). No significant differences were identified between groups in cytokine expression, TN mucus production and Ki67 expression (p>0.05). However, increased mucus production in TT was identified in the symbiotic group, compared with the control (p>0.05), as well as increased expression of Ki67 in the TN of both groups (p>0.05). Conclusion: The results of the present study demonstrated that preoperative symbiotic supplementation of patients with RCC undergoing tumor resection was able to modulate the intestinal microbiota, the production of SCFA and mucus, however, without repercussions on clinical outcomes.
publishDate 2023
dc.date.none.fl_str_mv 2023-10-17T13:41:11Z
2023-10-17T13:41:11Z
2023-05-29
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.publisher.none.fl_str_mv Universidade Federal de Minas Gerais
Brasil
FARMACIA - FACULDADE DE FARMACIA
Programa de Pós-Graduação em Ciência de Alimentos
UFMG
publisher.none.fl_str_mv Universidade Federal de Minas Gerais
Brasil
FARMACIA - FACULDADE DE FARMACIA
Programa de Pós-Graduação em Ciência de Alimentos
UFMG
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFMG
instname:Universidade Federal de Minas Gerais (UFMG)
instacron:UFMG
instname_str Universidade Federal de Minas Gerais (UFMG)
instacron_str UFMG
institution UFMG
reponame_str Repositório Institucional da UFMG
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repository.name.fl_str_mv Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)
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