RESUMO
The precise etiology of Inflammatory Bowel Disease (IDB) remains unclear and several factors are believed to play a role in its development and progression, including the composition of microbial communities resident in the gastrointestinal tract. Human intestinal microbiota are extensive with at least 15,000-36,000 bacterial species. However, thanks to the new development in sequencing and molecular taxonomic methodologies, our understanding of the microbiota population composition, dynamics, and ecology has greatly increased. Intestinal microbiota play a critical role in the maintenance of the host intestinal barrier homeostasis, while dysbiosis, which involves reduction in the microbiome diversity, can lead to progression of inflammatory disorders, such as IBD and colorectal cancer. It is hypothesized that fingerprinting characterization of the microbiota community composition is the first step in the study of this complex bacterial ecosystem and a crucial step in the targeted therapy. Molecular fingerprinting of human gastrointestinal tract microbiota could be performed by different techniques including the semi quantitation, 16SrRNA, the DNA- microarray as well as other relatively new methods which were developed to study many complex bacterial ecosystems. These techniques provide individual data and profiles, using fast and sensitive tools for the high taxonomic level fingerprint of the human intestinal microbiota and provide estimation of the relative presence of the microbial target groups within each individual. Such personalized information serves as a remarkable and unprecedented opportunity to improve targeted medical treatment and probably develop strategies to prevent disease.
Assuntos
Código de Barras de DNA Taxonômico/métodos , Impressões Digitais de DNA/métodos , Disbiose/microbiologia , Microbioma Gastrointestinal/genética , Trato Gastrointestinal/microbiologia , Doenças Inflamatórias Intestinais/microbiologia , Antibacterianos/uso terapêutico , Técnicas de Tipagem Bacteriana , Disbiose/diagnóstico , Disbiose/tratamento farmacológico , Disbiose/patologia , Trato Gastrointestinal/patologia , Homeostase , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Terapia de Alvo Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Medicina de Precisão , RNA Ribossômico 16S/genéticaRESUMO
It is well documented that nutraceuticals, in general, and Green tea catechins, in particular, possess a potential therapeutic value in inflammatory bowel diseases (IBD) due to their anti-oxidative and anti-inflammatory effects. This study aimed to investigate the possible mechanism of action of catechins in a rat model of colitis induced by 2.4.6 trinitrobenzene sulfonic acid (TNBS). Thirty-five young adult Sprague-Dawley rats were divided into four groups: normal control (n=5), catechins (n=9), TNBS (n=9) and TNBS plus catechins (n=12) treated. Catechin in the form of Epigallocatechin-3-gallate (EGCG) was administered daily by intraperitoneal injection, 1 week before the induction date of UC. Biopsies of the descending colon were collected on days 3, 10 and 17, and partly frozen for molecular studies or fixed for light microscopy. The status of intestinal tissue alterations and mast cells number were also assessed, as well as the mRNA expressions of IL-6, TNF-a and NF-kB, and determination of ROS expression. Histological data depicted a significant amelioration in the TNBS- and EGCG-treated rats compared to the non-treated animals. Catechin expressed strong anti-inflammatory and anti-oxidant effects, ameliorated ulcerative colitis and stabilized mast cells. The mechanism of action occurred basically through the NF-kB pathway and possibly through a crosstalk with other pathways.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Catequina/análogos & derivados , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Chá/química , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Catequina/isolamento & purificação , Catequina/farmacologia , Colite/induzido quimicamente , Colite/imunologia , Colite/patologia , Colo/imunologia , Colo/patologia , Regulação da Expressão Gênica , Interleucina-6/genética , Interleucina-6/imunologia , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/patologia , NF-kappa B/genética , NF-kappa B/imunologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/imunologia , Espécies Reativas de Oxigênio/metabolismo , Ácido Trinitrobenzenossulfônico , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Probiotics (PB) are living microorganisms that act as a commensal population in normal intestines and confer numerous beneficial effects on the host. The introduction of probiotics in the treatment of inflammatory bowel disease (IBD) prolongs remission. The aim of this study was to investigate the intestinal and hepatic effects of PB supplementation in an experimental IBD model in mice induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). In the first step of the experimental procedure, CD-1 male mice, 5 to 6 weeks old, were randomly divided into 3 groups and inoculated intrarectally with, respectively, saline, alcohol, or TNBS to assess the experimental IBD model. In the second step, mice treated, or not, with TNBS inoculation, were treated with PB (Lactobacillus Casei, Bifidobacterum Lactis) for 1, 2 or 3 weeks, on a daily basis. Large bowel (colon and rectum) and liver were processed for histological alterations, according to a scoring system. Large bowel was also assessed for apoptosis by TUNEL assay. TNBS induced, as expected, severe damage and inflammation in the large bowel, including nuclear alterations and apoptosis, and, to a lesser extent, to the liver. Administration of PB determined significant reduction of both histological alterations and apoptosis. PB administration in advance protects from inflammation. In conclusion, supplementation with Lactobacillus casei, Bifidobacterum lactis PB is able to ameliorate the colitis by reversing the histological changes caused by TNBS in mice. Experimentation in human subjects in needed to prove their efficacy in reducing histological alterations that may be present in subjects with IBD.
Assuntos
Bifidobacterium , Suplementos Nutricionais , Doenças Inflamatórias Intestinais , Mucosa Intestinal , Lacticaseibacillus casei , Fígado , Probióticos , Ácido Trinitrobenzenossulfônico/toxicidade , Animais , Humanos , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , CamundongosRESUMO
Inflammatory bowel disease (IBD) consists of two distinct clinical forms, ulcerative colitis (UC) and Crohn's disease (CD), with unknown aetiology, which nevertheless are considered to share almost identical pathophysiological backgrounds. Up to date, a full coherent mechanistic explanation for IBD is still lacking, but people start to realize that the pathogenesis of IBD involves four fundamental components: the environment, gut microbiota, the immune system and the genome. As a consequence, IBD development might be due to an altered immune response and a disrupted mechanism of host tolerance to the non-pathogenic resident microbiota, leading to an elevated inflammatory response. Considering the available data arising from the scientific literature, here reviewed, in CD, a benefit of probiotics remains unproven; in UC, a benefit of probiotics remains unproven, even if E. coli Nissle 1917 seems promising in maintaining remission and it could be considered an alternative in patients intolerant or resistant to 5-ASA preparations; in pouchitis, small controlled trials suggest a benefit from VSL no. 3 in the primary and secondary prevention of pouchitis; in IBD-associated conditions, a benefit of probiotics remains unproven. However, well-designed randomized control clinical trials are necessary to understand the undoubted role of these agents in the management of gut physiology in health and disease.