This study investigates the role of gut microbiota in stress resistance by examining the interactions between the gut, brain, and microbiota in mice. The authors found that stress resistance in mice was associated with a more abundant *Lactobacillus* and *Akkermansia* in the gut, while less abundant *Bacteroides*, *Alloprevotella*, *Helicobacter*, *Lachnoclostridium*, *Blautia*, *Roseburia*, *Coliexibacter*, and *Lachnospiraceae_NK4A136*. Stress-sensitive animals showed higher permeability and stronger immune responses in their colon, along with higher levels of pro-inflammatory cytokines in the serum. Their hippocampus also exhibited more extensive microglial activation, abnormal interactions between microglia and neurons, and lower synaptic plasticity. Transplanting fecal microbiota from stress-sensitive mice into naive ones perturbed microglia-neuron interactions and impaired synaptic plasticity, leading to more depression-like behavior after stress exposure. Conversely, transplanting fecal microbiota from stress-resistant mice protected microglia from activation and preserved synaptic plasticity, resulting in less depression-like behavior after stress exposure. These findings suggest that gut microbiota influence stress resilience by regulating microglia-neuron interactions in the hippocampus.This study investigates the role of gut microbiota in stress resistance by examining the interactions between the gut, brain, and microbiota in mice. The authors found that stress resistance in mice was associated with a more abundant *Lactobacillus* and *Akkermansia* in the gut, while less abundant *Bacteroides*, *Alloprevotella*, *Helicobacter*, *Lachnoclostridium*, *Blautia*, *Roseburia*, *Coliexibacter*, and *Lachnospiraceae_NK4A136*. Stress-sensitive animals showed higher permeability and stronger immune responses in their colon, along with higher levels of pro-inflammatory cytokines in the serum. Their hippocampus also exhibited more extensive microglial activation, abnormal interactions between microglia and neurons, and lower synaptic plasticity. Transplanting fecal microbiota from stress-sensitive mice into naive ones perturbed microglia-neuron interactions and impaired synaptic plasticity, leading to more depression-like behavior after stress exposure. Conversely, transplanting fecal microbiota from stress-resistant mice protected microglia from activation and preserved synaptic plasticity, resulting in less depression-like behavior after stress exposure. These findings suggest that gut microbiota influence stress resilience by regulating microglia-neuron interactions in the hippocampus.