This thesis explores how gut microbes adapt to host immune signals, focusing on transcriptional and metabolic changes in bacteria during inflammation. Using dual RNA-sequencing and targeted metabolomics, the study identifies unsaturated long-chain fatty acids (uLCFAs) as key host-derived molecules that modulate microbial gene expression, mimicking immune-driven adaptations. These lipid-mediated signals appear to shape bacterial functions across diverse taxa and immune conditions, underscoring their broad physiological importance. The work also refines microbial genome annotations, revealing previously unknown non-coding RNAs linked to stress tolerance and immune adaptation. Overall, the findings provide a mechanistic framework for how immune signals reshape gut microbial functions, highlighting potential microbiome-targeted strategies to influence immune responses with implications for therapeutic interventions in immune-related diseases.