LIVIA SAMARA DOS REIS RODRIGUES OKADA
Projetos de Pesquisa
Unidades Organizacionais
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
7 resultados
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- Gut microbiome composition in lean patients with NASH is associated with liver damage independent of caloric intake: A prospective pilot study(2018) DUARTE, S. M. B.; STEFANO, J. T.; MIELE, L.; PONZIANI, F. R.; SOUZA-BASQUEIRA, M.; OKADA, L. S. R. R.; COSTA, F. G. de Barros; TODA, A. K.; MAZO, D. F. C.; SABINO, E. C.; CARRILHO, F. J.; GASBARRINI, A.; OLIVEIRA, C. P.Background and Aim: The aim of the study was to compare the gut microbiomes from obese and lean patients with or without NASH to outline phenotypic differences. Methods and Results: We performed a cross-sectional pilot study comprising biopsy-proven NASH patients grouped according to BMI. Microbiome DNA was extracted from stool samples, and PCR amplification was performed using primers for the V4 region of the 16S rRNA gene. The amplicons were sequenced using the Ion PGM Torrent platform, and data were analyzed using QIIME software. Macronutrient consumption was analyzed by a 7-day food record. Liver fibrosis >= F2 was associated with increased abundance of Lactobacilli (p = 0.0007). NASH patients showed differences in Faecalibacterium, Ruminococcus, Lactobacillus and Bifidobacterium abundance compared with the control group. Lean NASH patients had a 3-fold lower abundance of Faecalibacterium and Ruminococcus (p = 0.004), obese NASH patients were enriched in Lactobacilli (p = 0.002), and overweight NASH patients had reduced Bifidobacterium (p = 0.018). Moreover, lean NASH patients showed a deficiency in Lactobacillus compared with overweight and obese NASH patients. This group also appeared similar to the control group with regard to gut microbiome alpha diversity. Although there were qualitative differences between lean NASH and overweight/obese NASH, they were not statistically significant (p = 0.618). The study limitations included a small sample size, a food questionnaire that collected only qualitative and semi-quantitative data, and variations in group gender composition that may influence differences in FXR signaling, bile acids metabolism and the composition of gut microbiota. Conclusion: Our preliminary finding of a different pathogenetic process in lean NASH patients needs to be confirmed by larger studies, including those with patient populations stratified by sex and dietary habits.
conferenceObject Molecular Characterization of the Fecal Microbiome in Brazilian Obese NASH patients compared to lean healthy controls.(2015) OLIVEIRA, Claudia P.; STEFANO, Jose Tadeu; RIBEIRO, Roberto M.; DUARTE, Sebastiao M.; RODRIGUES, Livia; CAMPOS, Priscila B.; COSTA, Fernando G.; MAZO, Daniel F.; CARRILHO, Flair J.; SABINO, Ester C.conferenceObject Plasma Proteomic Signature in Patients with Nash Treated with OMEGA-3: Perspectives of Knowing Mechanism of Action.(2018) OKADA, Livia Samara Reis Rodrigues; OLIVEIRA, Claudia P. M. S.; STEFANO, Jose Tadeu; NOGUEIRA, Monize Aydar; CORDEIRO, Fernanda Bertucce; ALVES, Venancio A. F.; TORRINHAS, Raquel Suzana; CARRILHO, Flair Jose; WAITZBERG, Dan Linetzky- Omega-3 PUFA modulate lipogenesis, ER stress, and mitochondrial dysfunction markers in NASH - Proteomic and lipidomic insight(2018) OKADA, Livia Samara dos Reis Rodrigues; OLIVEIRA, Claudia P.; STEFANO, Jose Tadeu; NOGUEIRA, Monize Aydar; SILVA, Ismael Dale Cotrim Guerreiro da; CORDEIRO, Fernanda Bertucce; ALVES, Venancio Avancini Ferreira; TORRINHAS, Raquel Susana; CARRILHO, Flair Jose; PURI, Puneet; WAITZBERG, Dan L.Background & aims: Currently there is no FDA-approved therapy for nonalcoholic steatohepatitis (NASH). Increased n-6/n-3 polyunsaturated fatty acids (PUFA) ratio can induce endoplasmic reticulum (ER) stress and mitochondrial dysfunction that characterize NASH. Our recent study with n-3 PUFA showed improvement in individual histologic parameters like steatosis, ballooning and lobular inflammation. We hypothesized that n-3 PUFA therapy mediated improvement in histologic parameters is modulated by lipidomic and proteomic changes. Methods: We therefore evaluated hepatic proteomic and plasma lipidomic profiles before and after n-3 PUFA therapy in subjects with NASH. In a double-blind, randomized, placebo-controlled trial, patients with NASH received 6-month treatment with n-3 PUFA (0.945 g/day [64% alpha-linolenic (ALA), 21% eicosapentaenoic (EPA), and 16% docosahexaenoic (DHA) acids]). Paired liver biopsy and plasma collected before and after-n-3 PUFA therapy were assessed using mass spectrometry and gas chromatography for hepatic proteomics and plasma lipidomics. Data were matched to UniProt and LIPID MAPS database, respectively. Cytoscape software was used to analyze functional pathways. Twenty-seven NASH patients with paired liver histology and plasma before and after n-3 PUFA treatment were studied. Results: Treatment with n-3 PUFA significantly increased ALA, EPA, and glycerophospholipids, and decreased arachidonic acid (p < 0.05 for all). Further, proteomic markers of cell matrix, lipid metabolism, ER stress and cellular respiratory pathways were also modulated. Interestingly, these alterations reflected functional changes highly suggestive of decreased cellular lipotoxicity potential; reduced ER proteasome degradation of proteins and induction of chaperones; and a shift in cell energy homeostasis towards mitochondrial beta-oxidation. Conclusion: Six-month treatment with omega-3 PUFAs significantly improved hepatic proteomic and plasma lipidomic markers of lipogenesis, endoplasmic reticulum stress and mitochondrial functions in patients with NASH.
conferenceObject The gut microbiome of lean patients with non-alcoholic steatohepatitis: comparison with overweight/obese counterparts and healthy subjects, correlation with dietary intake and liver histology(2017) DUARTE, S. M.; STEFANO, J. T.; MIELE, L.; PONZIANI, F. R.; SOUZA, M.; RODRIGUES, L.; COSTA, F. G.; TODA, K.; MAZO, D. F.; SABINO, E. C.; CARRILHO, F. J.; GASBARRINI, A.; OLIVEIRA, C. P.conferenceObject Omega-3 fatty acids improve proteomic and lipidomic markers of endoplasmic reticulum (ER) stress and mitochondrial dysfunction in a randomized controlled trial in subjects with Nonalcoholic Steatohepatitis(2015) RODRIGUES, Livia; OLIVEIRA, Claudia P.; STEFANO, Jose Tadeu; NOGUEIRA, Monize A.; SILVA, Ismael D.; TURCO, Edson G. Lo; ALVES, Venancio Avancini F.; CARRILHO, Flair J.; PURI, Puneet; WAITZBERG, Dan- Omega-3 polyunsaturated fatty acids in treating non-alcoholic steatohepatitis: A randomized, double-blind, placebo-controlled trial(2016) NOGUEIRA, Monize Aydar; OLIVEIRA, Claudia Pinto; ALVES, Venancio Avancini Ferreira; STEFANO, Jose Tadeu; RODRIGUES, Livia Samara dos Reis; TORRINHAS, Raquel Susana; COGLIATI, Bruno; BARBEIRO, Hermes; CARRILHO, Flair Jose; WAITZBERG, Dan LinetzkyBackground: & aims: Few clinical trials have addressed the potential benefits of omega-3 polyunsaturated fatty acids (PUFAs) on non-alcoholic steatohepatitis (NASH). We evaluated the effects of supplementation with omega-3 PUFAs from flaxseed and fish oils in patients with biopsy-proven NASH. Methods: Patients received three capsules daily, each containing 0315 g of omega-3 PUFAs (64% alpha-linolenic [ALA], 16% eicosapentaenoic [EPA], and 21% docosahexaenoic [DHA] acids; n-3 group, n = 27) or mineral oil (placebo group, n = 23). Liver biopsies were evaluated histopathologically by the NASH activity score (NAS). Plasma levels of omega-3 PUFAs were assessed as a marker of intake at baseline and after 6 months of treatment. Secondary endpoints included changes in plasma biochemical markers of lipid metabolism, inflammation, and liver function at baseline and after 3 and 6 months of treatment. Results: At baseline, NAS was comparable between the groups (p = 0.98). After intervention with omega 3 PUFAs, plasma ALA and EPA levels increased (p <= 0.05). However in the placebo group, we also observed increased EPA and DHA (p <= 0.05), suggesting an off-protocol intake of PUFAs. NAS improvement/stabilization was correlated with increased ALA in the n-3 group (p = 0.02) and with increased EPA (p = 0.04) and DHA (p = 0.05) in the placebo group. Triglycerides were reduced after 3 months in the n-3 group compared to baseline (p = 0.01). Conclusions: In NASH patients, the supplementation of omega-3 PUFA from flaxseed and fish oils significantly impacts on plasma lipid profile of patients with NASH. Plasma increase of these PUFAs was associated with better liver histology.