APC Microbiome Ireland - Journal Articles
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Item T lymphocyte plasticity in chronic inflammatory diseases: The emerging role of the Ikaros family as a key Th17-Treg switch(Elsevier B.V., 2024-12-30) Ramón-Vázquez, Ana; Flood, Peter; Cashman, Thuy Linh; P. Patil; Ghosh, Subrata; Science Foundation IrelandT helper (Th) 17 and regulatory T (Treg) cells are highly plastic CD4+ Th cell subsets, being able not only to actively adapt to their microenvironment, but also to interconvert, acquiring mixed identity markers. These phenotypic changes are underpinned by transcriptional control mechanisms, chromatin reorganization events and epigenetic modifications, that can be hereditable and stable over time. The Ikaros family of transcription factors have a predominant role in T cell subset specification through mechanisms of transcriptional program regulation that enable phenotypical diversification. They are crucial factors in maintaining Th17/Treg balance and therefore, homeostatic conditions in the tissues. However, they are also implicated in pathogenic processes, where their transcriptional repression contributes to the control of autoimmune processes. In this review, we discuss how T cell fate, specifically in humans, is regulated by the Ikaros family and its interplay with additional factors like the Notch signaling pathway, gut microbiota and myeloid-T cell interactions. Further, we highlight how the transcriptional activity of the Ikaros family impacts the course of T cell mediated chronic inflammatory diseases like rheumatoid and psoriatic arthritis, inflammatory bowel disease, systemic lupus erythematosus and multiple sclerosis. We conclude by discussing recently developed therapeutics designed to target Ikaros family members.Item Differential cortical aspartate uptake across the oestrous cycle is associated with changes in gut microbiota in Wistar-Kyoto rats(Elsevier B.V., 2024-12-26) Sajjad, Jahangir; Morael, Jennifer; Melo, Thieza G.; Foley, Tara; Murphy, Amy; Keane, James; Popov, Jelena; Stanton, Catherine; Dinan, Timothy G.; Clarke, Gerard; Cryan, John F.; Collins, James M.; O’Mahony, Siobhain M.; Science Foundation IrelandPain and psychological stress are intricately linked, with sex differences evident in disorders associated with both systems. Glutamatergic signalling in the central nervous system is influenced by gonadal hormones via the hypothalamic–pituitary–adrenal axis and is central in pain research. Emerging evidence supports an important role for the gut microbiota in influencing pain signalling. Here, the functional activity of excitatory amino acid transporters (EAATs) in the anterior cingulate cortex (ACC) and lumbosacral spinal cord of male and female Wistar-Kyoto rats, an animal model of comorbid visceral hypersensitivity and enhanced stress responsivity, was investigated across the oestrous cycle. Correlations between the gut microbiota and changes in the functional activity of the central glutamatergic system were also investigated. EAAT function in the lumbosacral spinal cord was similar between males and females across the oestrous cycle. EAAT function was higher in the ACC of dioestrus females compared to proestrus and oestrus females. In males, aspartate uptake in the ACC positively correlated with Bacteroides, while aspartate uptake in the spinal cord positively correlated with the relative abundance of Lachnospiraceae NK4A136. Positive associations with aspartate uptake in the spinal cord were also observed for Alistipes and Bifidobacterium during oestrus, and Eubacterium coprostanoligenes during proestrus. Clostridium sensu stricto1 was negatively associated with aspartate uptake in the ACC in males and dioestrus females. These data indicate that glutamate metabolism in the ACC is oestrous stage-dependent and that short-chain fatty acid-producing bacteria are positively correlated with aspartate uptake in males and during specific oestrous stages in females.Item Examining the healthy human microbiome concept(Springer Nature, 2024-10-23) Joos, Raphaela; Boucher, Katy; Lavelle, Aonghus; Arumugam, Manimozhiyan; Blaser, Martin J.; Claesson, Marcus J.; Clarke, Gerard; Cotter, Paul D.; De Sordi, Luisa; Dominguez-Bello, Maria G.; Dutilh, Bas E.; Ehrlich, Stanislav D.; Ghosh, Tarini Shankar; Hill, Colin; Junot, Christophe; Lahti, Leo; Lawley, Trevor D.; Licht, Tine R.; Maguin, Emmanuelle; Makhalanyane, Thulani P.; Marchesi, Julian R.; Matthijnssens, Jelle; Raes, Jeroen; Ravel, Jacques; Salonen, Anne; Scanlan, Pauline D.; Shkoporov, Andrey; Stanton, Catherine; Thiele, Ines; Tolstoy, Igor; Walter, Jens; Yang, Bo; Yutin, Natalia; Zhernakova, Alexandra; Zwart, Hub; Asnicar, Francesco; Typas, Athanasios; Betsou, Fay; Blottière, Hervé; Bork, Peer; Boutron, Isabelle; Carraturo, Federica; Claesson, Marcus; Cordaillat-Simmons, Magali; Druart, Celine; Fasano, Alessio; Godoy, Yolanda; Haller, Dirk; Hassani, Zahra; Hazenbrink, Diënty H. M. J.; Israelsen, Mads; Iyappan, Anandhi; Jarde, Alexander; Kampshoff, Stephan; Krag, Aleksander; Kriaa, Aicha; Lavelle, Aonghus; Metwaly, Amira; Morozova, Vitalina; Pinto, Federica; Pons, Nicolas; Prost, Pierre-Louis; Ravaud, Philippe; Rhimi, Moez; Rodriquez, Julie; Sarati, Arjun; Schierwagen, Robert; Segata, Nicola; Serra, Debora; Trebicka, Jonel; Vecchi, Corrado; Veiga, Patrick; Zitvogel, Laurence; Derosa, Lisa; Doré, Joël; Ross, R. Paul; Horizon 2020Human microbiomes are essential to health throughout the lifespan and are increasingly recognized and studied for their roles in metabolic, immunological and neurological processes. Although the full complexity of these microbial communities is not fully understood, their clinical and industrial exploitation is well advanced and expanding, needing greater oversight guided by a consensus from the research community. One of the most controversial issues in microbiome research is the definition of a ‘healthy’ human microbiome. This concept is complicated by the microbial variability over different spatial and temporal scales along with the challenge of applying a unified definition to the spectrum of healthy microbiome configurations. In this Perspective, we examine the progress made and the key gaps that remain to be addressed to fully harness the benefits of the human microbiome. We propose a road map to expand our knowledge of the microbiome–health relationship, incorporating epidemiological approaches informed by the unique ecological characteristics of these communities.Item Regional and conditional variability of FXR: new lessons on ileal inflammation and gut barrier functions(American Physiological Society, 2024-10-10) Joyce, Susan A.; O’Malley, DervlaItem Symposium: What does the microbiome tell us about prevention and treatment of AD/ADRD?(Society for Neuroscience, 2024-10-09) Capocchi, Joia K.; Figueroa-Romero, Claudia; Dunham, Sage J. B.; Faraci, Gina; Rothman, Jason A.; Whiteson, Katrine L.; Seo, Dong-oh; Holtzman, David M.; Grabrucker, Stefanie; Nolan, Yvonne M.; Kaddurah-Daouk, Rima; Jett, David A.; Good Ventures Foundation; Cure Alzheimer’s Fund; Science Foundation Ireland; National Institute on Aging; Foundation for the National Institutes of HealthAlzheimer's disease (AD) and Alzheimer's disease-related dementias (ADRDs) are broad-impact multifactorial neurodegenerative diseases. Their complexity presents unique challenges for developing effective therapies. This review highlights research presented at the 2024 Society for Neuroscience meeting which emphasized the gut microbiome's role in AD pathogenesis by influencing brain function and neurodegeneration through the microbiota–gut–brain axis. This emerging evidence underscores the potential for targeting the gut microbiota to treat AD/ADRD.