The gut microbiota plays a crucial role in the development of inflammatory depression, a treatment-resistant form of depression associated with low-grade inflammation. This study investigated the gut microbiota composition, inflammatory factors, and short-chain fatty acids (SCFAs) in patients with inflammatory depression and found that they had higher levels of pro-inflammatory bacteria such as Bacteroides and lower levels of SCFA-producing bacteria such as Clostridium. Fecal microbiota transplantation (FMT) and probiotic supplementation in animal experiments showed that disturbed gut microbiota can induce inflammatory depression by activating inflammatory pathways, while probiotic administration with Clostridium butyricum normalized gut microbiota, reduced inflammation, and exhibited antidepressant-like effects. Inflammatory depression is linked to increased pro-inflammatory cytokines such as IL-6, TNF-α, and CRP, and is associated with poor response to antidepressants. The gut microbiota can modulate the immune system and contribute to immune tolerance. Microbial-associated molecular patterns (MAMPs) can activate pattern recognition receptors (PRRs) such as TLRs and NLRs, leading to inflammation and neuroinflammation. SCFAs produced by the gut microbiota can affect immune and inflammatory responses and cross the blood-brain barrier to modulate brain function. The gut microbiota may influence depressive symptoms by regulating the peripheral and central immune systems. The study found that patients with inflammatory depression had altered gut microbiota composition, with increased pro-inflammatory bacteria and decreased SCFA-producing bacteria. The gut microbiota of patients with inflammatory depression showed increased inflammatory factors and intestinal mucosal permeability. Probiotic administration with Clostridium butyricum normalized gut microbiota, reduced inflammation, and improved depressive symptoms in a mouse model of inflammatory depression. The study highlights the importance of the gut microbiota in the pathogenesis of inflammatory depression and suggests that targeting the gut microbiota may be a potential therapeutic approach. However, the study has limitations, including a small sample size and the need for further clinical trials to confirm the efficacy of probiotics in treating inflammatory depression.The gut microbiota plays a crucial role in the development of inflammatory depression, a treatment-resistant form of depression associated with low-grade inflammation. This study investigated the gut microbiota composition, inflammatory factors, and short-chain fatty acids (SCFAs) in patients with inflammatory depression and found that they had higher levels of pro-inflammatory bacteria such as Bacteroides and lower levels of SCFA-producing bacteria such as Clostridium. Fecal microbiota transplantation (FMT) and probiotic supplementation in animal experiments showed that disturbed gut microbiota can induce inflammatory depression by activating inflammatory pathways, while probiotic administration with Clostridium butyricum normalized gut microbiota, reduced inflammation, and exhibited antidepressant-like effects. Inflammatory depression is linked to increased pro-inflammatory cytokines such as IL-6, TNF-α, and CRP, and is associated with poor response to antidepressants. The gut microbiota can modulate the immune system and contribute to immune tolerance. Microbial-associated molecular patterns (MAMPs) can activate pattern recognition receptors (PRRs) such as TLRs and NLRs, leading to inflammation and neuroinflammation. SCFAs produced by the gut microbiota can affect immune and inflammatory responses and cross the blood-brain barrier to modulate brain function. The gut microbiota may influence depressive symptoms by regulating the peripheral and central immune systems. The study found that patients with inflammatory depression had altered gut microbiota composition, with increased pro-inflammatory bacteria and decreased SCFA-producing bacteria. The gut microbiota of patients with inflammatory depression showed increased inflammatory factors and intestinal mucosal permeability. Probiotic administration with Clostridium butyricum normalized gut microbiota, reduced inflammation, and improved depressive symptoms in a mouse model of inflammatory depression. The study highlights the importance of the gut microbiota in the pathogenesis of inflammatory depression and suggests that targeting the gut microbiota may be a potential therapeutic approach. However, the study has limitations, including a small sample size and the need for further clinical trials to confirm the efficacy of probiotics in treating inflammatory depression.