Browsing by Author "Thomas, Andrew M."
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- Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent MechanismFachi, Jose Luis; Felipe, Jaqueline de Souza; Pral, Lais Passariello; da Silva, Bruna Karadi; Correa, Renan Oliveira; Pereira de Andrade, Mirella Cristiny; da Fonseca, Denise Morais; Basso, Paulo Jose; Saraiva Camara, Niels Olsen; de Sales e Souza, Ericka Lorenna; Martins, Flaviano dos Santos; Sato Guima, Suzana Eiko; Thomas, Andrew M.; Setubal, Joao Carlos; Magalhaes, Yuli Thamires; Forti, Fabio Luis; Candreva, Thamiris; Rodrigues, Hosana Gomes; de Jesus, Marcelo Bispo; Consonni, Silvio Roberto; Farias, Alessandro dos Santos; Varga-Weisz, Patrick; Ramirez Vinolo, Marco Aurelio (Cell Press, 2019-04-16)Antibiotic-induced dysbiosis is a key factor predisposing intestinal infection by Clostridium difficile. Here, we show that interventions that restore butyrate intestinal levels mitigate clinical and pathological features of C. difficile-induced colitis. Butyrate has no effect on C. difficile colonization or toxin production. However, it attenuates intestinal inflammation and improves intestinal barrier function in infected mice, as shown by reduced intestinal epithelial permeability and bacterial translocation, effects associated with the increased expression of components of intestinal epithelial cell tight junctions. Activation of the transcription factor HIF-1 in intestinal epithelial cells exerts a protective effect in C. difficile-induced colitis, and it is required for butyrate effects. We conclude that butyrate protects intestinal epithelial cells from damage caused by C. difficile toxins via the stabilization of HIF-1, mitigating local inflammatory response and systemic consequences of the infection.
- Gut Microbiota Profile of Obese Diabetic Women Submitted to Roux-en-Y Gastric Bypass and Its Association with Food Intake and Postoperative Diabetes RemissionAl Assal, Karina; Prifti, Edi; Belda, Eugeni; Sala, Priscila; Clement, Karine; Dao, Maria-Carlota; Dore, Joel; Levenez, Florence; Taddei, Carla R.; Fonseca, Danielle Cristina; Rocha, Ilanna Marques; Balmant, Bianca Depieri; Thomas, Andrew M.; Santo, Marco A.; Dias-Neto, Emmanuel; Setubal, Joao Carlos; Zucker, Jean-Daniel; Belarmino, Giliane; Torrinhas, Raquel Susana; Waitzberg, Dan L. (2020-02)Gut microbiota composition is influenced by environmental factors and has been shown to impact body metabolism. Objective: To assess the gut microbiota profile before and after Roux-en-Y gastric bypass (RYGB) and the correlation with food intake and postoperative type 2 diabetes remission (T2Dr). Design: Gut microbiota profile from obese diabetic women was evaluated before (n = 25) and 3 (n = 20) and 12 months (n = 14) after RYGB, using MiSeq Illumina-based V4 bacterial 16S rRNA gene profiling. Data on food intake (7-day record) and T2Dr (American Diabetes Association (ADA) criteria) were recorded. Results: Preoperatively, the abundance of five bacteria genera differed between patients with (57%) and without T2Dr (p < 0.050). Preoperative gut bacteria genus signature was able to predict the T2Dr status with 0.94 accuracy ROC curve (receiver operating characteristic curve). Postoperatively (vs. preoperative), the relative abundance of some gut bacteria genera changed, the gut microbial richness increased, and the Firmicutes to Bacteroidetes ratio (rFB) decreased (p < 0.05) regardless of T2Dr. Richness levels was correlated with dietary profile pre and postoperatively, mainly displaying positive and inverse correlations with fiber and lipid intakes, respectively (p < 0.05). Conclusions: Gut microbiota profile was influenced by RYGB and correlated with diet and T2Dr preoperatively, suggesting the possibility to assess its composition to predict postoperative T2Dr.
- Tissue-Associated Bacterial Alterations in Rectal Carcinoma Patients Revealed by 16S rRNA Community ProfilingThomas, Andrew M.; Jesus, Eliane C.; Lopes, Ademar; Aguiar, Samuel, Jr.; Begnami, Maria D.; Rocha, Rafael M.; Carpinetti, Paola Avelar; Camargo, Anamaria A.; Hoffmann, Christian; Freitas, Helano C.; Silva, Israel T.; Nunes, Diana N.; Setubal, Joao C.; Dias-Neto, Emmanuel (Frontiers, 2016-12-09)Sporadic and inflammatory forms of colorectal cancer (CRC) account for more than 80% of cases. Recent publications have shown mechanistic evidence for the involvement of gut bacteria in the development of both CRC-forms. Whereas, colon and rectal cancer have been routinely studied together as CRC, increasing evidence show these to be distinct diseases. Also, the common use of fecal samples to study microbial communities may reflect disease state but possibly not the tumor microenvironment. We performed this study to evaluate differences in bacterial communities found in tissue samples of 18 rectal-cancer subjects when compared to 18 non-cancer controls. Samples were collected during exploratory colonoscopy (non-cancer group) or during surgery for tumor excision (rectal-cancer group). High throughput 16S rRNA amplicon sequencing of the V4V5 region was conducted on the Ion PGM platform, reads were filtered using Qiime and clustered using UPARSE. We observed significant increases in species richness and diversity in rectal cancer samples, evidenced by the total number of OTUs and the Shannon and Simpson indexes. Enterotyping analysis divided our cohort into two groups, with the majority of rectal cancer samples clustering into one enterotype, characterized by a greater abundance of Bacteroides and Dorea. At the phylum level, rectal-cancer samples had increased abundance of candidate phylum OD1 (also known as Parcubacteria) whilst non-cancer samples had increased abundance of Planctomycetes. At the genera level, rectal-cancer samples had higher abundances of Bacteroides, Phascolarctobacterium, Parabacteroides, Desulfovibrio, and Odoribacter whereas non-cancer samples had higher abundances of Pseudomonas, Escherichia, Acinetobacter, Lactobacillus, and Bacillus. Two Bacteroides fragilis OTUs were more abundant among rectal-cancer patients seen through 16S rRNA amplicon sequencing, whose presence was confirmed by immunohistochemistry and enrichment verified by digital droplet PCR. Our findings point to increased bacterial richness and diversity in rectal cancer, along with several differences in microbial community composition. Our work is the first to present evidence for a possible role of bacteria such as B. fragilis and the phylum Parcubacteria in rectal cancer, emphasizing the need to study tissue-associated bacteria and specific regions of the gastrointestinal tract in order to better understand the possible links between the microbiota and rectal cancer.