Review
Food Science & Technology
Meng Ye, Juping Yu, Xuexia Shi, Jingyi Zhu, Xiangdong Gao, Wei Liu
Summary: The degradation processes of polysaccharides by human gut microbiota, with a focus on the role ofBacteroides thetaiotaomicron as a potential probiotic, have garnered attention in recent years. Researchers have summarized the degradation system and pathways of different polysaccharides byB. thetaiotaomicron, and provided insights into future developments in drug development, precision microbiology medicine, and personalized nutrition.
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
(2021)
Article
Multidisciplinary Sciences
Jennifer L. Modesto, Victoria H. Pearce, Guy E. Townsend
Summary: The presence of distinct glycans in heterogeneous mixtures is challenging to detect due to structural complexity and diversity. In this study, the authors exploit the sensing abilities of gut microbes to develop quantitative glycan biosensors. They couple the bacterial detection machinery with an optimized luciferase reporter to indicate the presence and abundance of compositionally similar, yet structurally distinct glycans. These tools can greatly enhance our understanding of the mammalian gut environment and identify host-microbial interactions critical for human health.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Declan A. Gray, Joshua B. R. White, Abraham O. Oluwole, Parthasarathi Rath, Amy J. Glenwright, Adam Mazur, Michael Zahn, Arnaud Basle, Carl Morland, Sasha L. Evans, Alan Cartmell, Carol Robinson, Sebastian Hiller, Neil A. Ranson, David N. Bolam, Bert van den Berg
Summary: This study characterized the role of the SusCD protein complex in glycan uptake in Bacteroidetes, shedding light on its function. The findings revealed key structural features and provided insights into substrate transport mechanisms.
NATURE COMMUNICATIONS
(2021)
Article
Infectious Diseases
Miad Elahi, Haruyuki Nakayama-Imaohji, Masahito Hashimoto, Ayano Tada, Hisashi Yamasaki, Tamiko Nagao, Tomomi Kuwahara
Summary: The gut symbiont Bacteroides thetaiotaomicron (BT) suppresses Clostridium difficile (CD) toxin production by inhibiting polysaccharide metabolism pathways. Polysaccharide fractions derived from BT can suppress CD toxin production, with cell wall-associated glycans playing a key role in this inhibitory effect.
Article
Biochemistry & Molecular Biology
Hiromi Shimokawa, Mikiyasu Sakanaka, Yuki Fujisawa, Hirokazu Ohta, Yuta Sugiyama, Shin Kurihara
Summary: This study investigated the polyamine biosynthetic enzyme N-carbamoylputrescine amidohydrolase (NCPAH) in Bacteroides thetaiotaomicron. The results showed that NCPAH converts N-carbamoylputrescine to putrescine, a precursor of spermidine. Furthermore, NCPAH activity is strongly inhibited by agmatine and spermidine, and moderately inhibited by putrescine, suggesting a role in intracellular polyamine homeostasis.
Article
Biochemistry & Molecular Biology
Weiwei Han, Bee-Zen Peng, Chunyan Wang, Guy E. Townsend II, Natasha A. Barry, Frank Peske, Andrew L. Goodman, Jun Liu, Marina Rodnina, Eduardo A. Groisman
Summary: Protein synthesis is a vital cellular process that requires a significant amount of energy. However, cells can sustain protein synthesis under starvation conditions through the use of a bacterial elongation factor called EF-C2, which promotes translocation without hydrolyzing GTP. EF-G2, a variant of EF-C2, is crucial for bacterial gut colonization and can sustain protein synthesis at slower rates. EF-G2 is more abundant than canonical EF-C1 and specifically accumulates during carbon starvation. A unique 26-residue region in EF-G2 is essential for protein synthesis, dissociation from the ribosome, and the absence of GTPase activity. These findings provide insights into how cells minimize energy consumption while maintaining protein synthesis in fluctuating nutrient environments.
Article
Microbiology
Nathan T. Porter, Johan Larsbrink
Summary: Members of the Bacteroides genus in the gut have remarkable abilities in degrading fiber polysaccharides and producing organic acids. However, little is known about the genes involved in downstream metabolic pathways. This study focused on several organic acid synthesis pathways in Bacteroides thetaiotaomicron and identified potential genes involved in each pathway. A plasmid system was also developed to alter gene expression levels. Understanding these pathways is important for improving human health and utilizing the bacteria.
MICROBIOLOGY SPECTRUM
(2022)
Article
Biology
Daniel Hoces, Giorgia Greter, Markus Arnoldini, Melanie L. Staubli, Claudia Moresi, Anna Sintsova, Sara Berent, Isabel Kolinko, Florence Bansept, Aurore Woller, Janine Hafliger, Eric Martens, Wolf-Dietrich Hardt, Shinichi Sunagawa, Claude Loverdo, Emma Slack
Summary: This study used genetically barcoded Bacteroides thetaiotaomicron strains to quantify population bottlenecks during colonization of the mouse gut. The results showed an inverse relationship between microbiota complexity and the colonization probability of wildtype B. theta clones. The polysaccharide capsule of B. theta is important for resistance against attacks, and the acapsular strain loses in competitive colonization.
Article
Multidisciplinary Sciences
Nathalie Bechon, Jovana Mihajlovic, Anne-Aurelie Lopes, Sol Vendrell-Fernandez, Julien Deschamps, Romain Briandet, Odile Sismeiro, Isabelle Martin-Verstraete, Bruno Dupuy, Jean-Marc Ghigo
Summary: This study found that bile triggers biofilm formation in B. thetaiotaomicron and other gut Bacteroidales species. Unlike many Firmicutes and Proteobacteria that rely on eDNA for biofilm formation, B. thetaiotaomicron requires BT3563-mediated eDNA degradation to form biofilms in the presence of bile.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Samuel Kwain, Brian N. Dominy, Kristi J. Whitehead, Brock A. Miller, Daniel C. Whitehead
Summary: In this study, a computational approach was used to explore the interactive mechanism between acarbose and SusG, and it was found that acarbose binds to SusG and inhibits its catalytic activity through a double-displacement catalytic mechanism. This computational strategy could be used for structure-based drug design to discover small molecules capable of inhibiting Bt Sus, providing a holistic approach for selective modulation of the GI microbiota.
CHEMICAL BIOLOGY & DRUG DESIGN
(2023)
Review
Biochemistry & Molecular Biology
Yong Lai, Naoki Hayashi, Timothy K. Lu
Summary: Recent progress in synthetic biology has opened up possibilities for engineering microbiomes. This review focuses on expanding the genetic toolkit for Bacteroides thetaiotaomicron and its potential applications in microbiome engineering. The authors also provide their perspective on the challenges and future opportunities for using gut-associated bacteria as living therapeutic agents.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Regis Stentz, Emily Jones, Rokas Juodeikis, Udo Wegmann, Maria Guirro, Andrew J. Goldson, Arlaine Brion, Catherine Booth, Padhmanand Sudhakar, Ian R. Brown, Tamas Korcsmaros, Simon R. Carding
Summary: The microbiota in the GIT plays a significant role in maintaining the host's health, and the interplay between microbes and host cells in the GIT is still not fully understood. This study investigates the proteins in bacterial extracellular vesicles (BEVs) produced by Bacteroides thetaiotaomicron in the GIT and their impact on host cell interactions. The researchers identified specific proteins enriched in BEVs produced in vivo, including dipeptidyl peptidases, an asparaginase, and a bile salt hydrolase, which can influence host cell biosynthetic pathways.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Xiaohong Yang, Xiaoxiao Yang, Hai Yu, Lan Na, Tamashree Ghosh, John B. McArthur, Tsui-Fen Chou, Patricia Dickson, Xi Chen
Summary: A study found a bacterial α-N-acetylglucosaminidase from gut symbiotic bacterium Bacteroides thetaiotaomicron, capable of efficiently cleaving N-acetylglucosamine from heparosan disaccharide. This enzyme could potentially serve as a useful catalyst for heparan sulfate analysis.
Article
Microbiology
Melissa C. Kordahi, Ian B. Stanaway, Marion Avril, Denise Chac, Marie-Pierre Blanc, Benjamin Ross, Christian Diener, Sumita Jain, Paul McCleary, Ana Parker, Vincent Friedman, Jennifer Huang, Wynn Burke, Sean M. Gibbons, Amy D. Willis, Richard P. Darveau, William M. Grady, Cynthia W. Ko, R. William DePaolo
Summary: This study provides fundamental insight into the microbial microenvironment of the pre-neoplastic polyp by highlighting strain-specific genomic and proteomic differences, as well as more broad compositional differences in the microbiome.
CELL HOST & MICROBE
(2021)
Article
Microbiology
Ju-Hyung Lee, Soo-Jeong Kwon, Ji-Yoon Han, Sang-Hyun Cho, Yong-Joon Cho, Joo-Hong Park
Summary: The study identifies a genetic determinant, BT2391, for Bacteroides thetaiotaomicron colonization in the gut. The BT2391 mutant shows increased competitive fitness and adherence ability, but it may promote colitis under specific dietary conditions.
JOURNAL OF MICROBIOLOGY
(2022)
Article
Chemistry, Applied
Molly Dorothy Pither, Anna Illiano, Chiara Pagliuca, Amy Jacobson, Giuseppe Mantova, Alessia Stornaiuolo, Roberta Colicchio, Mariateresa Vitiello, Gabriella Pinto, Alba Silipo, Michael A. Fischbach, Paola Salvatore, Angela Amoresano, Antonio Molinaro, Flaviana Di Lorenzo
Summary: Bacteroides thetaiotaomicron, a symbiont of the human gut, is extensively studied, but little is known about its cell envelope's interaction with the immune system. This research investigates the structure and immunostimulatory properties of its lipopolysaccharide (LPS). The study reveals that the rough-type LPS produced by B. thetaiotaomicron promotes TLR2-mediated immune response but has a weak ability to engage the MD-2/TLR4 pathway.
CARBOHYDRATE POLYMERS
(2022)
Article
Microbiology
Yijun Zhu, Mohammed Dwidar, Ina Nemet, Jennifer A. Buffa, Naseer Sangwan, Xinmin S. Li, James T. Anderson, Kymberleigh A. Romano, Xiaoming Fu, Masanori Funabashi, Zeneng Wang, Pooja Keranahalli, Shawna Battle, Aaron N. Tittle, Adeline M. Hajjar, Valentin Gogonea, Michael A. Fischbach, Joseph A. DiDonato, Stanley L. Hazen
Summary: Recent studies have shown the critical role of gut microbiota in metabolizing dietary phenylalanine into phenylacetic acid (PAA), which is important for the production of phenylacetylglutamine (PAGln) linked to atherosclerotic cardio-vascular disease (ASCVD). Researchers have identified two different microbial pathways, involving phenylpyruvate:ferre-doxin oxidoreductase (PPFOR) and phenylpyruvate decarboxylase (PPDC), for PAA formation in the gut. The abundance of these pathways is significantly higher in ASCVD patients compared to controls. These findings provide insights into the therapeutic targeting of PAGln formation in vivo.
CELL HOST & MICROBE
(2023)
Editorial Material
Urology & Nephrology
Leah Guthrie, Justin. L. L. Sonnenburg, Michael. A. A. Fischbach, Timothy. W. W. Meyer
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Virology
Jessica Spring, Vera Beilinson, Brian C. DeFelice, Juan M. Sanchez, Michael Fischbach, Alexander Chervonsky, Tatyana Golovkina
Summary: Both viruses and bacteria can produce molecular patterns that affect microbial pathogenesis and anti-microbial responses. In addition, bacteria produce metabolites, while viruses can change the metabolic profiles of infected cells. Using an unbiased metabolomics approach, this study found that viral infection significantly alters the metabolite profile of mice monocolonized with Lactobacillus murinus. These findings suggest that the changes in metabolites could play a role in viral pathogenesis or the host response against the virus, providing a new avenue for future investigations.
Article
Multidisciplinary Sciences
Kali M. Pruss, Haoqing Chen, Yuanyuan Liu, William Van Treuren, Steven K. Higginbottom, John B. Jarman, Curt R. Fischer, Justin Mak, Beverly Wong, Tina M. Cowan, Michael A. Fischbach, Justin L. Sonnenburg, Dylan Dodd
Summary: The human gut microbiota produces various small molecules that have significant effects on host physiology. However, little is known about the origin and fate of these metabolites. In this study, researchers identified a co-metabolic pathway between the host and gut bacteria for the production of hippuric acid, a major organic acid in mammalian urine. They found that gut bacteria convert phenylalanine to phenylpropionic acid, which is then re-oxidized by the host using medium-chain acyl-CoA dehydrogenase (MCAD). Through experiments with germ-free mice, the researchers also identified other microbial metabolites processed by MCAD in the host circulation. This study reveals a novel mechanism by which mammals metabolize microbiota-derived metabolites and highlights the importance of host-microbe co-metabolism in the generation and processing of these metabolites.
NATURE COMMUNICATIONS
(2023)
Review
Hematology
Christina Lamers, Daniel Ricklin, John D. Lambris
Summary: The number of complement inhibitors approved for therapeutic use or in late-stage clinical trials has expanded rapidly in recent years. The sudden emergence of this area in biotech start-ups and pharmaceutical companies is surprising considering the well-established involvement of the complement system in various clinical conditions. However, the complement system has unique characteristics that have delayed its recognition as a traditional drug target, such as concerns about safety and the complexity of its involvement in biological processes.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Min Wang, Lucas J. Osborn, Sunit Jain, Xiandong Meng, Allison Weakley, Jia Yan, William J. Massey, Venkateshwari Varadharajan, Anthony Horak, Rakhee Banerjee, Daniela S. Allende, E. Ricky Chan, Adeline M. Hajjar, Zeneng Wang, Alejandra Dimas, Aishan Zhao, Kazuki Nagashima, Alice G. Cheng, Steven Higginbottom, Stanley L. Hazen, J. Mark Brown, Michael A. Fischbach
Summary: By constructing variant communities of a complex defined microbial community, we found that removing specific strains occupying the bile acid 7a-dehydroxylation niche resulted in significant changes in the community composition and function. Strains that are functionally redundant within a niche can have differential impacts outside the niche, leading to unpredictable effects on unrelated community-level phenotypes. This study highlights the complexity of the gut microbiome and the importance of understanding individual strain dynamics in the context of the entire community.
Article
Biotechnology & Applied Microbiology
Victoria Pascal Andreu, Hannah E. E. Augustijn, Lianmin Chen, Alexandra Zhernakova, Jingyuan Fu, Michael A. A. Fischbach, Dylan Dodd, Marnix H. H. Medema
Summary: Profile hidden Markov models are used to identify taxon-specific primary metabolic pathways. The gut microbiota produce various small molecules that modulate host physiology. The gutSMASH algorithm is introduced to identify primary metabolic gene clusters in high-quality microbial genomes, revealing marked differences in pathway distribution among phyla and indicating a characteristic metabolic niche for each taxon. The study also highlights the crucial role of pathway-specific gene regulation and metabolite flux in microbiome-derived metabolites.
NATURE BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Y. Erin Chen, Djenet Bousbaine, Alessandra Veinbachs, Katayoon Atabakhsh, Alex Dimas, Victor K. Yu, Aishan Zhao, Nora J. Enright, Kazuki Nagashima, Yasmine Belkaid, Michael A. Fischbach
Summary: Certain bacterial colonists induce a specific T cell response, even in the absence of infection. By engineering a skin bacterium to express tumor antigens, researchers were able to elicit tumor-specific T cells that infiltrate lesions and possess cytotoxic activity. This reveals the potential for commensal bacteria to be harnessed therapeutically for targeted immune responses.
Article
Cell Biology
Amelie Kuhn, Jana Riegger, Graciosa Q. Teixeira, Markus Huber-Lang, John D. Lambris, Cornelia Neidlinger-Wilke, Rolf E. Brenner
Summary: Terminal complement complex deposition was found in human degenerated discs. The study investigated the mechanisms and effects of terminal complement activation in annulus fibrosus (AF) cells. Complement inhibitors effectively suppressed anaphylatoxin generation and TCC deposition induced by zymosan. Gene expression of ADAMTS4, MMP1, and COX2 was influenced by C3 and C5 blockade. Degenerated endplate tissue secreted soluble factors that enhanced direct C5 cleavage. These findings suggest the functional involvement of terminal complement activation in disc degeneration and the role of degenerated tissue in complement activation.
Article
Cardiac & Cardiovascular Systems
Ina Nemet, Xinmin S. Li, Arash Haghikia, Lin Li, Jennifer Wilcox, Kymberleigh A. Romano, Jennifer A. Buffa, Marco Witkowski, Ilja Demuth, Maximilian Koenig, Elisabeth Steinhagen-Thiessen, Fredrik Backhed, Michael A. Fischbach, W. H. Wilson Tang, Ulf Landmesser, Stanley L. Hazen
Summary: Precision microbiome modulation has the potential to be a new treatment strategy for cardiovascular disease. This study used stable isotope dilution mass spectrometry to measure gut microbial metabolites and found that certain metabolites derived from aromatic amino acids are associated with adverse cardiovascular outcomes.
EUROPEAN HEART JOURNAL
(2023)
Article
Multidisciplinary Sciences
Kazuki Nagashima, Aishan Zhao, Katayoon Atabakhsh, Minwoo Bae, Jamie E. Blum, Allison Weakley, Sunit Jain, Xiandong Meng, Alice G. Cheng, Min Wang, Steven Higginbottom, Alex Dimas, Pallavi Murugkar, Elizabeth S. Sattely, James J. Moon, Emily P. Balskus, Michael A. Fischbach
Summary: Certain bacterial strains from the microbiome induce a potent T cell response, and many T cells in the gut repertoire recognize multiple bacterial strains. 13 T cell clones show a one-to-many TCR-to-strain relationship, recognizing 18 Firmicutes strains.
Article
Microbiology
Ina Nemet, Masanori Funabashi, Xinmin S. Li, Mohammed Dwidar, Naseer Sangwan, Sarah M. Skye, Kymberleigh A. Romano, Tomas Cajka, Brittany D. Needham, Sarkis K. Mazmanian, Adeline M. Hajjar, Federico E. Rey, Oliver Fiehn, W. H. Wilson Tang, Michael A. Fischbach, Stanley L. Hazen
Summary: pCS and IS, gut microbiome-derived metabolites, are associated with cardiovascular disease risks and all-cause mortality. Microbial genes involved in the production of these metabolites can confer pro-thrombotic phenotype in vivo. Therapeutic targeting of gut microbial pathways may be a rational approach for CVD treatment.
Meeting Abstract
Biochemistry & Molecular Biology
Christina Lamers, Martin Smiesko, Xiaoguang Xue, H. Van Son, Bea Wagner, G. Sfyroera, Nadja Berger, Piet Gros, John D. Lambris, Daniel Ricklin
MOLECULAR IMMUNOLOGY
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Richard Pouw, Joyce de Paula Souza, Jonas Kost, Said Rabbani, John Lambris, Daniel Ricklin
MOLECULAR IMMUNOLOGY
(2022)