• Fisheries and Aquatic Sciences
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• 제25권3호
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• pp.117-139
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• 2022

Synucleinopathies such as Parkinson's disease (PD) are incurable neurodegenerative conditions characterised by the abnormal aggregation of α-synuclein protein in neuronal cells. In PD, fibrillary synuclein aggregation forms Lewy bodies and Lewy neurites in the substantia nigra and cortex on the brain. Dementia with Lewy bodies and multiple system atrophy are also associated with α-synuclein protein abnormalities. α-synuclein is one of three synuclein proteins, and while its precise function is still unknown, one hypothesis posits that α-synuclein propagates from the enteric nervous system through the vagus nerve and into the brain, resulting in synucleinopathy. Studies on synucleinopathies should thus encompass not only the central nervous system but must necessarily include the gut and microbiome. The zebrafish (Danio rerio) is a well-established model for human neuronal pathologies and have been used in studies ranging from genetic models of hereditary disorders to neurotoxin-induced neurodegeneration as well as gut-brain-axis studies. There is significant genetic homology between zebrafish and mammalian vertebrates which is what makes the zebrafish so amenable to modelling human conditions but in the case of synucleinopathies, the zebrafish notably does not possess an α-synuclein homolog. Synuclein orthologs are present in the zebrafish however, and transgenic zebrafish that carry human α-synuclein have been generated. In addition, the zebrafish is a highly advantageous model and ideal replacement for reducing the use of mammalian models. This review discusses the application of the zebrafish as a model for synucleinopathies in efforts to further understand synuclein function and explore therapeutic strategies.

• IMMUNE NETWORK
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• 제24권3호
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• pp.20.1-20.21
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• 2024

The brain and lungs, vital organs in the body, play essential roles in maintaining overall well-being and survival. These organs interact through complex and sophisticated bi-directional pathways known as the 'lung-brain axis', facilitated by their close proximity and neural connections. Numerous studies have underscored the mediation of the lung-brain axis by inflammatory responses and hypoxia-induced damage, which are pivotal to the progression of both pulmonary and neurological diseases. This review aims to delve into how pulmonary diseases, including acute/chronic airway diseases and pulmonary conditions, can instigate neurological disorders such as stroke, Alzheimer's disease, and Parkinson's disease. Additionally, we highlight the emerging research on the lung microbiome which, drawing parallels between the gut and lungs in terms of microbiome contents, may play a significant role in modulating brain health. Ultimately, this review paves the way for exciting avenues of future research and therapeutics in addressing respiratory and neurological diseases.

• 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.

• Journal of Dairy Science and Biotechnology
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• 제36권3호
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• pp.133-145
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• 2018

Breastfeeding is highly recommended due to its benefits for both the infant and mother; however, most mothers predominantly use formula feed. Breastfeeding affords protection against a wide variety of medical conditions that may emerge at different time points over the lifespan, including hospital admissions for respiratory infections and neonatal fever, offspring childhood obesity, and cancer as well as cardiovascular disease, hyperlipidemia, hypertension, and diabetes. Moreover, breastfeeding is expected to decrease the risk of adolescent depression and other psychopathologies. It is also important for the development of the gut, gut-brain axis, and immune system, and night-time breast milk is likely to have higher antioxidant, anti-inflammatory, and immune regulatory effects due to the impact of breast milk melatonin on the infant's developing microbiome and gut permeability. Melatonin can be added to a night-time-specific formula feed; however, it is not included in the Korean Food Additive Codex.

• 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 Neurogastroenterology and Motility
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• 제24권4호
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• pp.512-527
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• 2018

This review provides a comprehensive overview of brain imaging studies of the brain-gut interaction in functional gastrointestinal disorders (FGIDs). Functional neuroimaging studies during gut stimulation have shown enhanced brain responses in regions related to sensory processing of the homeostatic condition of the gut (homeostatic afferent) and responses to salience stimuli (salience network), as well as increased and decreased brain activity in the emotional response areas and reduced activation in areas associated with the top-down modulation of visceral afferent signals. Altered central regulation of the endocrine and autonomic nervous responses, the key mediators of the brain-gut axis, has been demonstrated. Studies using resting-state functional magnetic resonance imaging reported abnormal local and global connectivity in the areas related to pain processing and the default mode network (a physiological baseline of brain activity at rest associated with self-awareness and memory) in FGIDs. Structural imaging with brain morphometry and diffusion imaging demonstrated altered gray- and white-matter structures in areas that also showed changes in functional imaging studies, although this requires replication. Molecular imaging by magnetic resonance spectroscopy and positron emission tomography in FGIDs remains relatively sparse. Progress using analytical methods such as machine learning algorithms may shift neuroimaging studies from brain mapping to predicting clinical outcomes. Because several factors contribute to the pathophysiology of FGIDs and because its population is quite heterogeneous, a new model is needed in future studies to assess the importance of the factors and brain functions that are responsible for an optimal homeostatic state.

• Journal of Microbiology and Biotechnology
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• 제34권3호
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• pp.487-494
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• 2024

Recently, the term metabiotics has emerged as a new concept of probiotics. This concept entails combining existing probiotic components with metabolic by-products improve specific physiological functionalities. Representative ingredients of these metabiotics include short-chain fatty acids (SCFAs), bacteriocins, polysaccharides, and peptides. The new concept is highly regarded as it complements the side effects of existing probiotics and is safe and easy to administer. Known health functions of metabiotics are mainly immune regulation, anti-inflammatory, anticancer, and brain-neurological health. Research has been actively conducted on the health benefits related to the composition of intestinal microorganisms. Among them, the focus has been on brain neurological health, which requires extensive research. This study showed that neurological disorders, such as depression, anxiety, autism spectrum disorder, Alzheimer's disease, and Parkinson's disease, can be treated and prevented according to the gut-brain axis theory by changing the intestinal microflora. In addition, various studies are being conducted on the immunomodulatory and anticancer effects of substances related to metabiotics of the microbiome. In particular, its efficacy is expected to be confirmed through human studies on various cancers. Therefore, developing various health functional effects of the next-generation probiotics such as metabiotics to prevent or treatment of various diseases is anticipated.

• 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.

• 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.

• Clinical Psychopharmacology and Neuroscience
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• 제16권4호
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• pp.422-433
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• 2018

Objective: Neuropsychiatric manifestations like depression and cognitive dysfunction commonly occur in inflammatory bowel disease (IBD). In the context of the brain-gut axis model, colitis can lead to alteration of brain function in a bottom-up manner. Here, the changes in the response of the hypothalamic-pituitary-adrenal axis and inflammation-related markers in the brain in colitis were studied. Methods: Dextran sodium sulfate (DSS) was used to generate a mouse model of colitis. Mice were treated with DSS for 3 or 7 days and sacrificed. We analyzed the gene expression of brain-derived neurotrophic factor (BDNF), cyclooxygenase 2 (COX-2), and glial fibrillary acidic protein (GFAP), and the expression of GFAP, in the hippocampus, hypothalamus, and amygdala. Additionally, the levels of C-reactive protein (CRP) and serum cortisol/corticosterone were measured. Results: Alteration of inflammatory-related markers varied depending on the brain region and exposure time. In the hippocampus, COX-2 mRNA, GFAP mRNA, and GFAP expression were upregulated during exposure to DSS. However, in the hypothalamus, COX-2 mRNA was upregulated only 3 days after treatment. In the amygdala, BDNF and COX-2 mRNAs were downregulated. CRP and corticosterone expression increased with DSS treatment at day 7. Conclusion: IBD could lead to neuroinflammation in a bottom-up manner, and this effect varied according to brain region. Stress-related hormones and serum inflammatory markers, such as CRP, were upregulated from the third day of DSS treatment. Therefore, early and active intervention is required to prevent psychological and behavioral changes caused by IBD, and region-specific studies can help understand the precise mechanisms by which IBD affects the brain.