Innate immune system signaling and intestinal dendritic cells migration to the brain underlie behavioral changes after microbial colonization in adult mice

作者：Vivek M. Philip, Narjis Kraïmi, Hailong Zhang, Jun Lü, Giada De Palma, Chiko Shimbori, Kathy D. McCoy, Siegfried Hapfelmeier, Olivier P. Schären, Andrew J. Macpherson, Fernando G. Chirdo, Michael G. Surette, Elena F. Verdú, Fang Liu, Stephen M. Collins, Přemysl Berčík · 发表于：Brain Behavior and Immunity · 年份：2025 · DOI：10.1016/j.bbi.2025.03.012 · 被引用次数：6 · 研究领域：Gut microbiota and health、Vagus Nerve Stimulation Research、Neuroinflammation and Neurodegeneration Mechanisms

• Altered microbiota is a key factor in disorders of gut-brain interaction (DGBI) • Microbial colonization induces changes in behavior and brain via innate immunity. • Microbial colonization activates multiple neuro-immune networks in gut and brain. • Behavioral change is mediated by CD11b + CD11c + CD103 + dendritic cell migration to the brain. Accumulating evidence suggests the microbiota is a key factor in Disorders of Gut-Brain Interaction (DGBI), by affecting host immune and neural systems. However, the underlying mechanisms remain elusive due to their complexity and clinical heterogeneity of patients with DGBIs. We aimed to identify neuroimmune pathways that are critical in microbiota-gut-brain communication during de novo gut colonization. We employed a combination of gnotobiotic and state-of-the-art microbial tools, behavioral analysis, immune and pharmacological approaches. Germ-free wild type, TLR signaling-deficient MyD88 -/- Ticam1 -/- and lymphocyte-deficient SCID mice were studied before and after colonization with specific pathogen-free microbiota, Altered Schaedler Flora, E. coli or S. typhimurium (permanent or transient colonizers) . TLR agonists and antagonists, CCR7 antagonist or immunomodulators were used to study immune pathways. We assessed brain c-Fos, brain-derived neurotrophic factor, and dendritic and glial cells by immunofluorescence, expression of neuroimmune genes by NanoString and performed brain proteomics. Bacterial monocolonization, convention...