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Lactobacillus reuteri ATG-F4 Alleviates Chronic Stress-induced Anhedonia by Modulating the Prefrontal Serotonergic System

Authors
Lee, JiyunKim, Eum-JiPark, Gun-SeokKim, Jeong seopKim, Tae-EunLee, Yoo JinPark, JuyiKang, JiheeKoo, Ja WookChoi, Tae Yong
Issue Date
Oct-2023
Publisher
한국뇌신경과학회
Keywords
Lactobacillus reuteri; Anhedonia; Prefrontal cortex; Serotonin
Citation
Experimental Neurobiology, v.32, no.5, pp 313 - 327
Pages
15
Journal Title
Experimental Neurobiology
Volume
32
Number
5
Start Page
313
End Page
327
URI
http://scholarworks.bwise.kr/kbri/handle/2023.sw.kbri/1075
DOI
10.5607/en23028
ISSN
1226-2560
2093-8144
Abstract
Mental health is influenced by the gut-brain axis; for example, gut dysbiosis has been observed in patients with major depressive disorder (MDD). Gut microbial changes by fecal microbiota transplantation or probiotics treatment reportedly modulates depressive symptoms. However, it remains unclear how gut dysbiosis contributes to mental dysfunction, and how correction of the gut microbiota alleviates neuropsychiatric disorders. Our previous study showed that chronic consumption of Lactobacillus reuteri ATG-F4 (F4) induced neurometabolic alterations in healthy mice. Here, we investigated whether F4 exerted therapeutic effects on depressive-like behavior by influencing the central nervous system. Using chronic unpredictable stress (CUS) to induce anhedonia, a key symptom of MDD, we found that chronic F4 consumption alleviated CUS-induced anhedonic behaviors, accompanied by biochemical changes in the gut, serum, and brain. Serum and brain metabolite concentrations involved in tryptophan metabolism were regulated by CUS and F4. F4 consumption reduced the elevated levels of serotonin (5-HT) in the brain observed in the CUS group. Additionally, the increased expression of Htr1a, a subtype of the 5-HT receptor, in the medial prefrontal cortex (mPFC) of stressed mice was restored to levels observed in stress-naïve mice following F4 supplementation. We further demonstrated the role of Htr1a using AAV-shRNA to downregulate Htr1a in the mPFC of CUS mice, effectively reversing CUS-induced anhedonic behavior. Together, our findings suggest F4 as a potential therapeutic approach for relieving some depressive symptoms and highlight the involvement of the tryptophan metabolism in mitigating CUS-induced depressive-like behaviors through the action of this bacterium.
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