Immunoregulatory role of the gut microbiota in inflammatory depression

Penghong Liu, Zhifen Liu, Jizhi Wang, Junyan Wang, Mingxue Gao, Yanyan Zhang, Chunxia Yang, Aixia Zhang, Gaizhi Li, Xinrong Li, Sha Liu, Lixin Liu, Ning Sun () and Kerang Zhang ()
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Penghong Liu: First Hospital of Shanxi Medical University
Zhifen Liu: First Hospital of Shanxi Medical University
Jizhi Wang: First Hospital of Shanxi Medical University
Junyan Wang: First Hospital of Shanxi Medical University
Mingxue Gao: First Hospital of Shanxi Medical University
Yanyan Zhang: First Hospital of Shanxi Medical University
Chunxia Yang: First Hospital of Shanxi Medical University
Aixia Zhang: First Hospital of Shanxi Medical University
Gaizhi Li: First Hospital of Shanxi Medical University
Xinrong Li: First Hospital of Shanxi Medical University
Sha Liu: First Hospital of Shanxi Medical University
Lixin Liu: First Hospital of Shanxi Medical University
Ning Sun: First Hospital of Shanxi Medical University
Kerang Zhang: First Hospital of Shanxi Medical University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Inflammatory depression is a treatment-resistant subtype of depression. A causal role of the gut microbiota as a source of low-grade inflammation remains unclear. Here, as part of an observational trial, we first analyze the gut microbiota composition in the stool, inflammatory factors and short-chain fatty acids (SCFAs) in plasma, and inflammatory and permeability markers in the intestinal mucosa of patients with inflammatory depression (ChiCTR1900025175). Gut microbiota of patients with inflammatory depression exhibits higher Bacteroides and lower Clostridium, with an increase in SCFA-producing species with abnormal butanoate metabolism. We then perform fecal microbiota transplantation (FMT) and probiotic supplementation in animal experiments to determine the causal role of the gut microbiota in inflammatory depression. After FMT, the gut microbiota of the inflammatory depression group shows increased peripheral and central inflammatory factors and intestinal mucosal permeability in recipient mice with depressive and anxiety-like behaviors. Clostridium butyricum administration normalizes the gut microbiota, decreases inflammatory factors, and displays antidepressant-like effects in a mouse model of inflammatory depression. These findings suggest that inflammatory processes derived from the gut microbiota can be involved in neuroinflammation of inflammatory depression.

Date: 2024
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DOI: 10.1038/s41467-024-47273-w

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