• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제31권3호
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• pp.131-145
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• 2020

The microbiota-gut-brain axis, which refers to the bidirectional communication pathway between gut bacteria and the central nervous system, has a profound effect on important brain processes, from the synthesis of neurotransmitters to the modulation of complex behaviors such as sociability and anxiety. Previous studies have revealed that the gut microbiota is potentially related to not only gastrointestinal disturbances, but also social impairment and repetitive behavior-core symptoms of autism spectrum disorder (ASD). Although studies have been conducted to characterize the microbial composition in patients with ASD, the results are heterogeneous. Nevertheless, it is clear that there is a difference in the composition of the gut microbiota between ASD and typically developed individuals, and animal studies have repeatedly suggested that the gut microbiota plays an important role in ASD pathophysiology. This possibility is supported by abnormalities in metabolites produced by the gut microbiota and the association between altered immune responses and the gut microbiota observed in ASD patients. Based on these findings, various attempts have been made to use the microbiota in ASD treatment. The results reported to date suggest that microbiota-based therapies may be effective for ASD, but largescale, well-designed studies are needed to confirm this.

• Journal of Ginseng Research
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• 제46권3호
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• pp.464-472
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• 2022

Background: Gut microbiota influence the central nervous system through gut-brain-axis. They also affect the neurological disorders. Gut microbiota differs in patients with Alzheimer's disease (AD), as a potential factor that leads to progression of AD. Oral intake of Korean Red Ginseng (KRG) improves the cognitive functions. Therefore, it can be proposed that KRG affect the microbiota on the gut-brain-axis to the brain. Methods: Tg2576 were used for the experimental model of AD. They were divided into four groups: wild type (n = 6), AD mice (n = 6), AD mice with 30 mg/kg/day (n = 6) or 100 mg/kg/day (n = 6) of KRG. Following two weeks, changes in gut microbiota were analyzed by Illumina HiSeq4000 platform 16S gene sequencing. Microglial activation were evaluated by quantitative Western blot analyses of Iba-1 protein. Claudin-5, occludin, laminin and CD13 assay were conducted for Blood-brain barrier (BBB) integrity. Amyloid beta (Aβ) accumulation demonstrated through Aβ 42/40 ratio was accessed by ELISA, and cognition were monitored by Novel object location test. Results: KRG improved the cognitive behavior of mice (30 mg/kg/day p < 0.05; 100 mg/kg/day p < 0.01), and decreased Aβ 42/40 ratio (p < 0.01) indicating reduced Aβ accumulation. Increased Iba-1 (p < 0.001) for reduced microglial activation, and upregulation of Claudin-5 (p < 0.05) for decreased BBB permeability were shown. In particular, diversity of gut microbiota was altered (30 mg/kg/day q-value<0.05), showing increased population of Lactobacillus species. (30 mg/kg/day 411%; 100 mg/kg/day 1040%). Conclusions: KRG administration showed the Lactobacillus dominance in the gut microbiota. Improvement of AD pathology by KRG can be medicated through gut-brain axis in mice model of AD.

• IMMUNE NETWORK
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• 제21권3호
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• pp.20.1-20.18
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• 2021

The gut is an important organ with digestive and immune regulatory function which consistently harbors microbiome ecosystem. The gut microbiome cooperates with the host to regulate the development and function of the immune, metabolic, and nervous systems. It can influence disease processes in the gut as well as extra-intestinal organs, including the brain. The gut closely connects with the central nervous system through dynamic bidirectional communication along the gut-brain axis. The connection between gut environment and brain may affect host mood and behaviors. Disruptions in microbial communities have been implicated in several neurological disorders. A link between the gut microbiota and the brain has long been described, but recent studies have started to reveal the underlying mechanism of the impact of the gut microbiota and gut barrier integrity on the brain and behavior. Here, we summarized the gut barrier environment and the 4 main gut-brain axis pathways. We focused on the important function of gut barrier on neurological diseases such as stress responses and ischemic stroke. Finally, we described the impact of representative environmental sensors generated by gut bacteria on acute neurological disease via the gut-brain axis.

• Journal of Ginseng Research
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• 제45권6호
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• pp.706-716
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• 2021

Background: Irritable bowel syndrome (IBS), the most common functional gastrointestinal disorder, is characterized by chronic abdominal pain and bowel habit changes. Although diverse complicated etiologies are involved in its pathogenesis, a dysregulated gut-brain axis may be an important factor. Red ginseng (RG), a traditional herbal medicine, is proven to have anti-inflammatory effects and improve brain function; however, these effects have not been investigated in IBS. Methods: Three-day intracolonic zymosan injections were used to induce post-infectious human IBS-like symptoms in mice. The animals were randomized to receive either phosphate-buffered saline (CG) or RG (30/100/300 mg/kg) for 10 days. Amitriptyline and sulfasalazine were used as positive controls. Macroscopic scoring was performed on day 4. Visceral pain and anxiety-like behaviors were assessed by colorectal distension and elevated plus maze and open field tests, respectively, on day 10. Next-generation sequencing of gut microbiota was performed, and biomarkers involved in gut-brain axis responses were analyzed. Results: Compared to CG, RG significantly decreased the macroscopic score, frequency of visceral pain, and anxiety-like behavior in the IBS mice. These effects were comparable to those after sulfasalazine and amitriptyline treatments. Moreover, RG significantly increased the proliferation of beneficial microbes, including Lactobacillus johnsonii, Lactobacillus reuteri, and Parabacteroides goldsteinii. RG significantly suppressed expression of IL-1β and c-fos in the gut and prefrontal cortex, respectively. Further, it restored the plasma levels of corticosterone to within the normal range, accompanied by an increase in adrenocorticotropic hormone. Conclusion: RG may be a potential therapeutic option for the management of human IBS.

• Journal of Ginseng Research
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• 제47권2호
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• pp.255-264
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• 2023

Background: Red ginseng (RG) alleviates psychiatric disorders. Fermented red ginseng (fRG) alleviates stress-induced gut inflammation. Gut dysbiosis causes psychiatric disorders with gut inflammation. To understand the gut microbiota-mediated action mechanism of RG and fRG against anxiety/depression (AD), we investigated the effects of RG, fRG, ginsenoside Rd, and 20(S)-β-D-glucopyranosyl protopanaxadiol (CK) on gut microbiota dysbiosis-induced AD and colitis in mice. Methods: Mice with AD and colitis were prepared by exposing to immobilization stress (IS) or transplanting the feces of patients with ulcerative colitis and depression (UCDF). AD-like behaviors were measured in the elevated plus maze, light/dark transition, forced swimming, and tail suspension tests. Results: Oral gavage of UCDF increased AD-like behaviors and induced neuroinflammation, gastrointestinal inflammation, and gut microbiota fluctuation in mice. Oral administration of fRG or RG treatment reduced UCDF-induced AD-like behaviors, hippocampal and hypothalamic IL-6 expression, and blood corticosterone level, whereas UCDF-suppressed hippocampal BDNF⁺NeuN⁺ cell population and dopamine and hypothalamic serotonin levels increased. Furthermore, their treatments suppressed UCDF-induced colonic inflammation and partially restored UCDF-induced gut microbiota fluctuation. Oral administration of fRG, RG, Rd, or CK also decreased IS-induced AD-like behaviors, blood IL-6 and corticosterone and colonic IL-6 and TNF-α levels, and gut dysbiosis, while IS-suppressed hypothalamic dopamine and serotonin levels increased. Conclusion: Oral gavage of UCDF caused AD, neuroinflammation, and gastrointestinal inflammation in mice. fRG mitigated AD and colitis in UCDF-exposed mice by the regulation of the microbiota-gut-brain axis and IS-exposed mice by the regulation of the hypothalamic-pituitary-adrenal axis.

• Journal of Microbiology and Biotechnology
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• 제32권7호
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• pp.927-937
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• 2022

To confirm the therapeutic effect of the water extract from Ecklonia cava (WEE) against PM_2.5 induced systemic health damage, we evaluated gut health with a focus on the microbiota and metabolites. Systemic damage in mice was induced through PM_2.5 exposure for 12 weeks in a whole-body chamber. After exposure for 12 weeks, body weight and food intake decreased, and WEE at 200 mg/kg body weight (mpk) alleviated these metabolic efficiency changes. In addition, PM_2.5 induced changes in the length of the colon and fecal water content. The administration of the WEE at 200 mpk oral dose effectively reduced changes in the colon caused by PM_2.5 exposure. We also attempted to confirm whether the effect of the WEE is mediated via regulation of the microbiota-gut-brain axis in mice with PM_2.5 induced systemic damage. We examined changes in the fecal microbiota and gut metabolites such as short-chain fatty acids (SCFAs) and kynurenine metabolites. In the PM_2.5 exposed group, a decrease in the abundance of Lactobacillus (Family: Lactobacillaceae) and an increase in the abundance of Alistipes (Family: Rikenellaceae) were observed, and the administration of the WEE showed a beneficial effect on the gut microbiota. In addition, the WEE effectively increased the levels of SCFAs (acetate, propionate, and butyrate). Furthermore, kynurenic acid (KYNA), which is a critical neuroprotective metabolite in the gut-brain axis, was increased by the administration of the WEE. Our findings suggest that the WEE could be used as a potential therapeutic against PM_2.5 induced health damage by regulating gut function.

• Journal of Microbiology and Biotechnology
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• 제33권10호
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• pp.1376-1383
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• 2023

Recent studies have confirmed that gut microbiota differs according to race or country in many diseases, including mild cognitive impairment (MCI) and Alzheimer's disease. However, no study has analyzed the characteristics of Korean MCI patients. This study was performed to observe the association between gut microbiota and MCI in the Korean elderly and to identify potential markers for Korean MCI patients. For this purpose, we collected fecal samples from Korean subjects who were divided into an MCI group (n = 40) and control group (n = 40) for 16S rRNA gene amplicon sequencing. Although no significant difference was observed in the overall microbial community profile, the relative abundance of several genera, including Bacteroides, Prevotella, and Akkermansia, showed significant differences between the two groups. In addition, the relative abundance of Prevotella was negatively correlated with that of Bacteroides (r = 0.733). This study may provide Korean-specific basic data for comparing the characteristics of the gut microbiota between Korean and non-Korean MCI patients.

• 생명과학회지
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• 제28권11호
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• pp.1386-1395
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• 2018

최근의 연구결과를 통해서 중추 신경계와 위장관은 장-뇌 축을 따라서 양방향의 상호작용이 일어나고 있다는 것이 분명해지고 있다. 전임상 연구로부터 장내 마이크로비오타가 다양한 생리적 기능을 통해서 중추 신경계의 기능을 조절할 수 있음이 밝혀지고 있다. 폴리페놀 화합물은 과일, 채소, 차, 커피, 와인과 같은 식품에 존재하는 식물 유래의 물질로, 항산화, 항염증, 항균, 면역 조절, 항암, 혈관 확장 및 프리바이오틱스와 유사한 효과를 보유하고 있어 식이를 통해 섭취할 경우 건강에 직접적인 효과를 나타낸다. 최근 들어 폴리페놀 화합물이 인지 기능뿐만 아니라 산화적 스트레스 및 염증성 손상에 대해 작용하는 신경 보호에 유익한 효과를 줄 수 있다는 증거가 보고되고 있다. 본 총설에서는 신경 세포 신호 전달 경로의 자극, 신경 염증, 혈관 기능 및 장내 마이크로비옴과의 상호작용에 따른 폴리페놀 화합물의 신경 보호 효과와 관련된 작용 메커니즘에 대한 일반적인 개요를 제시한다. 폴리페놀 화합물의 대사 산물은 혈액-뇌 장벽을 가로 지르는 신경 전달 물질을 이용하고 뇌 혈관 시스템을 조절하여 작용하거나, 간접적으로 장내 마이크로비오타에 작용한다. 또한, 폴리페놀 화합물은 노화 관련 인지 기능 저하 및 신경 퇴행과 같은 신경계 질환을 다양한 생리 기능을 통해 효과적으로 관리할수 있다는 사실이 제시되고 있다. 폴리페놀 화합물은 신경 염증을 감소시키고 기억과 인지 기능을 향상 시키며 장내 마이크로비오타를 조절하는 능력을 지니고 있기 때문에 신경계 질환의 예방 및 치료에 있어 잠재적인 기능성 식품으로 주목 받을 것으로 기대된다.

• Biomolecules & Therapeutics
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• 제31권4호
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• pp.417-424
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• 2023

Parkinson's disease (PD) which has various pathological mechanisms, recently, it is attracting attention to the mechanism via microbiome-gut-brain axis. 6-Shogaol, a representative compound of ginger, have been known for improving PD phenotypes by reducing neuroinflammatory responses. In the present study, we investigated whether 6-shogaol and ginger attenuate degeneration induced by Proteus mirabilis (P. mirabilis) on the intestine and brain, simultaneously. C57BL/6J mice received P. mirabilis for 5 days. Ginger (300 mg/kg) and 6-shogaol (10 mg/kg) were treated by gavage feeding for 22 days including the period of P. mirabilis treatment. Results showed that 6-shogaol and ginger improved motor dysfunction and dopaminergic neuronal death induced by P. mirabilis treatment. In addition, they suppressed P. mirabilis-induced intestinal barrier disruption, pro-inflammatory signals such as toll-like receptor and TNF-α, and intestinal α-synuclein aggregation. Moreover, ginger and 6-shogaol significantly inhibited neuroinflammation and α-synuclein in the brain. Taken together, 6-shogaol and ginger have the potential to ameliorate PD-like motor behavior and degeneration of dopaminergic neurons induced by P. mirabilis in mice. Here, these findings are meaningful in that they provide the first experimental evidence that 6-shogaol might attenuate PD via regulating gut-brain axis.

• 한국축산식품학회지
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• 제43권6호
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• pp.1044-1054
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• 2023

Growing evidence indicates a crucial role of the gut microbiota in physiological functions. Gut-brain axis imbalance has also been associated with neuropsychiatric and neurodegenerative disorders. Studies have suggested that probiotics regulate the stress response and alleviate mood-related symptoms. In this study, we investigated the effects of the probiotic Lacticaseibacillus rhamnosus IDCC3201 (L3201) on the behavioral response and fecal metabolite content in an unpredictable chronic mild stress (UCMS) mouse model. Our study shows that chronic stress in mice for three weeks resulted in significant changes in behavior, including lower locomotor activity, higher levels of anxiety, and depressive-like symptoms, compared to the control group. Metabolomic analysis demonstrated that disrupted fecal metabolites associated with aminoacyl-tRNA biosynthesis and valine, leucine, and isoleucine biosynthesis by UCMS were restored with the administration of L3201. Oral administration of the L3201 ameliorated the observed changes and improved the behavioral alterations along with fecal metabolites, suggesting that probiotics play a neuroprotective role.