Chronic stress is a major risk factor for depression and anxiety. However, individuals differ markedly in stress susceptibility and resilience. Accumulating preclinical and clinical evidence indicates that the gut microbiota is closely associated with stress-related phenotypes through the immune, endocrine, and neural pathways. Alterations in microbial diversity, short-chain fatty acid production, and tryptophan metabolism have been associated with stress-related neuroendocrine and immune regulation, whereas emerging preclinical evidence suggests potential links to neural circuits involved in reward processing. By integrating findings from microbiome research and systems neuroscience, this review proposes a microbiology-centered framework for understanding stress resilience and stress-induced anhedonia. Beyond merely summarizing the existing evidence, we critically evaluate the methodological challenges in current human and preclinical studies and highlight the critical need for standardized approaches and multi-omics integration to decipher causality and develop precise psychobiotic interventions.