리모실락토바실러스 퍼멘텀 균주의 정신생물학적 효과: 제브라피쉬 스트레스 모델을 이용한 비교 연구
Psychobiotic Effects of Limosilactobacillus fermentum Strains: A Comparative Study in Zebrafish Stress Model
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Objectives The gut–brain axis has been implicated in the pathophysiology of depression. Probiotics, particularly those derived from the infant gut, are emerging as promising psychobiotic agents due to their immunomodulatory and neurochemical properties. This study aimed to compare the psychobiotic potential of different Limosilactobacillus fermentum strains isolated from infant feces in a zebrafish model of unpredictable chronic stress (UCS). Methods Adult zebrafish were exposed to UCS for 14 days and orally administered one of three Limosilactobacillus fermentum strains (IR51, IM57, IR62) for two weeks following stress exposure. Behavioral assessments were conducted in week 5 using the novel tank test and social preference test. Gut microbiota were analyzed via 16S rRNA sequencing. Gene expression in the telencephalon, and intestinal tissue was assessed by quantitative polymerase chain reaction. Results Among the tested strains, IR62 most effectively reduced anxiety-like behaviors, evidenced by decreased bottom-dwelling time (IR62=45.55±0.91 sec vs. normal diet [ND]=50.83±0.73 sec, p<0.001) reduced latency to reach the top zone (IR62=38.29±2.00 sec vs. ND=43.25±1.61 sec, p<0.001) and decreased shoal cohesion (IR62=33.82±0.65 sec vs. ND=35.74±1.49 sec, p<0.05). IR62 restored gut microbial β-diversity and selectively increased health-associated genera such as Cetobacterium, while reducing potential pathobionts like Plesiomonas. In the telencephalon, IR62 markedly upregulated bdnf (false discovery rate-adjusted p=0.002), il-10 (p=0.002), and vmat2 (p=0.002). In the intestine, IR62 uniquely enhanced zo1.1 expression (p=0.007), a tight-junction gene critical for barrier integrity. Conclusions L. fermentum IR62 ameliorates anxiety-like behaviors in zebrafish exposed to chronic stress, likely via modulation of gut microbiota and telencephalic neuroimmune pathways. These findings support the therapeutic potential of infant-derived probiotics for gut–brain axis interventions in anxiety disorders.
Abstract
Objectives The gut–brain axis has been implicated in the pathophysiology of depression. Probiotics, particularly those derived from the infant gut, are emerging as promising psychobiotic agents due to their immunomodulatory and neurochemical properties. This study aimed to compare the psychobiotic potential of different Limosilactobacillus fermentum strains isolated from infant feces in a zebrafish model of unpredictable chronic stress (UCS). Methods Adult zebrafish were exposed to UCS for 14 days and orally administered one of three Limosilactobacillus fermentum strains (IR51, IM57, IR62) for two weeks following stress exposure. Behavioral assessments were conducted in week 5 using the novel tank test and social preference test. Gut microbiota were analyzed via 16S rRNA sequencing. Gene expression in the telencephalon, and intestinal tissue was assessed by quantitative polymerase chain reaction. Results Among the tested strains, IR62 most effectively reduced anxiety-like behaviors, evidenced by decreased bottom-dwelling time (IR62=45.55±0.91 sec vs. normal diet [ND]=50.83±0.73 sec, p<0.001) reduced latency to reach the top zone (IR62=38.29±2.00 sec vs. ND=43.25±1.61 sec, p<0.001) and decreased shoal cohesion (IR62=33.82±0.65 sec vs. ND=35.74±1.49 sec, p<0.05). IR62 restored gut microbial β-diversity and selectively increased health-associated genera such as Cetobacterium, while reducing potential pathobionts like Plesiomonas. In the telencephalon, IR62 markedly upregulated bdnf (false discovery rate-adjusted p=0.002), il-10 (p=0.002), and vmat2 (p=0.002). In the intestine, IR62 uniquely enhanced zo1.1 expression (p=0.007), a tight-junction gene critical for barrier integrity. Conclusions L. fermentum IR62 ameliorates anxiety-like behaviors in zebrafish exposed to chronic stress, likely via modulation of gut microbiota and telencephalic neuroimmune pathways. These findings support the therapeutic potential of infant-derived probiotics for gut–brain axis interventions in anxiety disorders.