Browsing by Author "Costa, Diogo Alpuim"
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- Gut microbiota profile of COVID-19 patients: prognosis and risk stratification (microCOVID-19 study)Publication . Nobre, José Guilherme; Delgadinho, Mariana; Silva, Carina; Mendes, Joana; Mateus, Vanessa; Ribeiro, Edna; Costa, Diogo Alpuim; Lopes, Miguel; Pedroso, Ana Isabel; Trigueiros, Frederico; Rodrigues, Maria Inês; Sousa, Cristina Lino de; Brito, MiguelBackground: Gut microbiota is intrinsically associated with the immune system and can promote or suppress infectious diseases, especially viral infections. This study aims to characterize and compare the microbiota profile of infected patients with SARS-CoV-2 (milder or more severe symptoms), non-infected people, and recovered patients. This is a national, transversal, observational, multicenter, and case-control study that analyzed the microbiota of COVID-19 patients with mild or severe symptoms at home, at the hospital, or in the intensive care unit, patients already recovered, and healthy volunteers cohabiting with COVID-19 patients. DNA was isolated from stool samples and sequenced in a NGS platform. A demographic questionnaire was also applied. Statistical analysis was performed in SPSS. Results: Firmicutes/Bacteroidetes ratios were found to be significantly lower in infected patients (1.61 and 2.57) compared to healthy volunteers (3.23) and recovered patients (3.89). Furthermore, the microbiota composition differed significantly between healthy volunteers, mild and severe COVID-19 patients, and recovered patients. Furthermore, Escherichia coli, Actinomyces naeslundii, and Dorea longicatena were shown to be more frequent in severe cases. The most common COVID-19 symptoms were linked to certain microbiome groups. Conclusion: We can conclude that microbiota composition is significantly affected by SARS-CoV-2 infection and may be used to predict COVID-19 clinical evolution. Therefore, it will be possible to better allocate healthcare resources and better tackle future pandemics.
- Human microbiota and breast cancer: is there any relevant link? A literature review and new horizons toward personalised medicinePublication . Costa, Diogo Alpuim; Nobre, José Guilherme; Batista, Marta Vaz; Ribeiro, Catarina; Calle, Catarina; Cortes, Alfonso; Marhold, Maximilian; Negreiros, Ida; Borralho, Paula; Brito, Miguel; Cortes, Javier; Braga, Sofia Azambuja; Costa, LuísBreast cancer (BC) is the most common malignancy and the second cause of cancer-specific death in women from high-income countries. Recently, gut microbiota dysbiosis emerged as a key player that may directly and/or indirectly influence the development, treatment, and prognosis of BC through diverse biological processes: host cell proliferation and death, immune system function, chronic inflammation, oncogenic signaling, hormonal and detoxification pathways. Gut colonization occurs during the prenatal period and is later diversified over distinct phases throughout life. In newly diagnosed postmenopausal BC patients, an altered fecal microbiota composition has been observed compared with healthy controls. Particularly, β-glucuronidase bacteria seem to modulate the enterohepatic circulation of estrogens and their resorption, increasing the risk of hormone-dependent BC. Moreover, active phytoestrogens, short-chain fatty acids, lithocholic acid, and cadaverine have been identified as bacterial metabolites influencing the risk and prognosis of BC. As in the gut, links are also being made with local microbiota of tumoural and healthy breast tissues. In breast microbiota, different microbial signatures have been reported, with distinct patterns per stage and biological subtype. Total bacterial DNA load was lower in tumor tissue and advanced-stage BC when compared with healthy tissue and early-stage BC, respectively. Hypothetically, these findings reflect local dysbiosis, potentially creating an environment that favors breast tumor carcinogenesis (oncogenic trigger), or the natural selection of microorganisms adapted to a specific microenvironment. In this review, we discuss the origin, composition, and dynamic evolution of human microbiota, the links between gut/breast microbiota and BC, and explore the potential implications of metabolomics and pharmacomicrobiomics that might impact BC development and treatment choices toward more personalized medicine. Finally, we put in perspective the potential limitations and biases regarding the current microbiota research and provide new horizons for stronger accurate translational and clinical studies that are needed to better elucidate the complex network of interactions between host, microorganisms, and drugs in the field of BC.
- Using Portuguese BRCA pathogenic variation as a model to study the impact of human admixture on human healthPublication . Andaluz, Stephanie; Zhao, Bojin; Sinha, Siddharth; Lagniton, Philip Naderev Panuringan; Costa, Diogo Alpuim; Ding, Xiaofan; Brito, Miguel; Wang, San MingBackground: Admixture occurs between different ethnic human populations. The global colonization in recent centuries by Europeans led to the most significant admixture in human history. While admixture may enhance genetic diversity for better fitness, it may also impact on human health by transmitting genetic variants for disease susceptibility in the admixture population. The admixture by Portuguese global exploration initiated in the 15th century has reached over 20 million of Portuguese-heritage population worldwide. It provides a valuable model to study the impact of admixture on human health. BRCA1 and BRCA2 (BRCA) are two of the important tumor suppressor genes. The pathogenic variation (PV) in BRCA is well determined to cause a high risk of hereditary breast and ovarian cancer. Tracing the distribution of Portuguese BRCA PV in the Portuguese-heritage population will help to understand the impact of admixture on cancer susceptibility in modern humans. In this study, we analyzed the distribution of the Portuguese-originated BRCA variation in the Brazilian population, which has a high degree of Portuguese heritage. Methods: By comprehensive data mining, standardization, and annotation, we generated a Portuguese-derived BRCA variation dataset and a Brazilian-derived BRCA variation dataset. We compared the two BRCA variation datasets to identify the BRCA variants shared between the two populations. Results: The Portuguese-derived BRCA variation dataset consists of 220 BRCA variants including 78 PVs from 11,482 Portuguese cancer patients, 93 (42.2%) in BRCA1 and 127 (57.7%) in BRCA2. Of the 556 Portuguese BRCA PV carriers carrying the 78 PVs, 331 (59.5%) carried the three Portuguese-BRCA founder PVs of BRCA1 c.2037delinsCC, BRCA1 c.3331_3334del and BRCA2 c.156_157insAlu. The Brazilian-derived BRCA variation dataset consists of 255 BRCA PVs from 7,711 cancer patients, 136 (53.3%) in BRCA1 and 119 (46.6%) in BRCA2. We developed an open database named dbBRCA-Portuguese (https://genemutation.fhs.um.edu.mo/dbbrca-portuguese/) and an open database named dbBRCA-Brazilian (https://genemutation.fhs.um.edu.mo/dbbrca-brazilian) to host the BRCA variation data from Portuguese and Brazilian populations. We compared the BRCA PV datasets between Portuguese and Brazilian populations and identified 29 Portuguese-specific BRCA PVs shared between Portuguese and Brazilian populations, 14 in BRCA1 including the Portuguese founder BRCA1 c.3331_3334del and BRCA1 c.2037delinsCC, and 15 in BRCA2 including the Portuguese founder BRCA2 c.156_157insAlu. Searching the 78 Portuguese BRCA PVs in over 5,000 ancient human genomes identified evolution origin for only 8 PVs in Europeans dated between 37,470 and 3,818 years before the present, confirming the Portuguese-specificity of Portuguese BRCA PVs; comparing the 78 Portuguese BRCA PVs Portuguese, 255 Brazilian BRCA PVs, and 134 African BRCA PVs showed little overlapping, ruling out the possibility that the BRCA PVs shared between Portuguese and Brazilian may also be contributed by African. Conclusion: Our study provides evidence that the admixture in recent human history contributed to cancer susceptibility in modern humans.