Disordered gut microbiota and changes in short-chain fatty acids and inflammatory processes in stress-vulnerable mice

• Published in: Journal of neuroimmunology Vol. 383; p. 578172
• Main Authors: Han, Wenjuan, Zheng, Yaxin, Wang, Lan, An, Cuixia
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15-10-2023
• Subjects: Chronic stress; Depression; Gut microbiota; Inflammation; Short-chain fatty acids; Gut microbiota; Short-chain fatty acids; Depression; Chronic stress; Inflammation
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2023.578172

Long-term exposure to chronic stress increases the incidence of depression. However, chronic stress is an associated risk factor in only a subset of individuals. Inflammation has been identified as a putative mechanism promoting stress vulnerability. Because of the gut microbiota's potential role as a source of inflammatory substances, short-chain fatty acids (SCFAs) may exert their influence on inflammation, emotional states, and cognition via the gut-brain axis. In this study, Classic behavioral tests were used to categorize C57BL/6 J mice into a CUMS-vulnerable and a CUMS-resilient group after they were exposed to chronic unpredictable mild stress (CUMS). We compared the 16S ribosomal RNA (rRNA) gene sequences retrieved from fecal samples between control, CUMS-vulnerable, and CUMS-resilient mice. SCFAs in fecal samples were detected by liquid chromatography and gas chromatography–mass spectrometry. Hippocampal cytokine production and TLR4/MYD88/NF-κB inflammatory pathway activation were evaluated using enzyme-linked immunosorbent assays (ELISAs) and western blotting. Then, we supplemented SCFAs in CUMS mice. we observed depression-like behavior and the expression of TLR4/MYD88/NF-κB inflammatory pathway in hippocampus of SCFAs supplementation mice. Susceptible mice to CUMS showed more severe symptoms of depression and anxiety, α diversity was significantly different, as well as higher expression of interleukin (IL)-1β and TLR4/MYD88/NF-κB inflammatory pathway components in the hippocampus. SCFA levels in the feces were significantly higher in CUMS-resilient mice than in control mice. Depressive behavior was reversed in CUMS-SCFAs group, and the protein level of TLR4/MYD88/NF-κB in hippocampus was decreased. Overall, these results provide new light on the possible involvement of the microbiome in the gut-brain axis development in depressive disorder and provide a theoretical basis for identifying novel therapeutic targets.
•Mice exposed to CUMS stress don't always exhibit symptoms of depression and anxiety.•The gut microbiota and SCFA levels changed in mice under chronic stress.•CUMS-vulnerable showed more intestinal microbiota diversity.•UMS-vulnerable showed higher MYD88, NF-κB, and TLR4 protein levels.•The CUMS-resilient group had considerably greater SCFA levels.