• 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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• 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.

• Biomolecules & Therapeutics
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• 제32권4호
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• pp.403-423
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• 2024

The human gastrointestinal (GI) tract houses a diverse microbial community, known as the gut microbiome comprising bacteria, viruses, fungi, and protozoa. The gut microbiome plays a crucial role in maintaining the body's equilibrium and has recently been discovered to influence the functioning of the central nervous system (CNS). The communication between the nervous system and the GI tract occurs through a two-way network called the gut-brain axis. The nervous system and the GI tract can modulate each other through activated neuronal cells, the immune system, and metabolites produced by the gut microbiome. Extensive research both in preclinical and clinical realms, has highlighted the complex relationship between the gut and diseases associated with the CNS, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review aims to delineate receptor and target enzymes linked with gut microbiota metabolites and explore their specific roles within the brain, particularly their impact on CNS-related diseases.

• 운동영양학회지
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• 제24권1호
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• pp.14-18
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• 2020

[Purpose] Functional foods are thought to strongly influence the structure and function of the brain. Previous studies have reported that brain-boosting diets may enhance neuroprotective functions. Certain foods are particularly rich in nutrients like phytochemicals that are known to support brain plasticity; such foods are commonly referred to as brain foods. [Methods] In this review, we briefly explore the scientific evidence supporting the neuroprotective activity of a number of phytochemicals with a focus on phenols and polyunsaturated fatty acids such as flavonoid, olive oil, and omega-3 fatty acid. [Results] The aim of this study was to systematically examine the primary issues related to phytochemicals in the brain. These include (a) the brain-gut-microbiome axis; (b) the effects of phytochemicals on gut microbiome and their potential role in brain plasticity; (c) the role of polyunsaturated fatty acids in brain health; and (d) the effects of nutrition and exercise on brain function. [Conclusion] This review provides evidence supporting the view that phytochemicals from medicinal plants play a vital role in maintaining brain plasticity by influencing the brain-gut-microbiome axis. The consumption of brain foods may have neuroprotective effects, thus protecting against neurodegenerative disorders and promoting brain health.

• 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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• 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.

• 정신신체의학
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• 제20권2호
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• pp.135-138
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• 2012

기능성 위장관 장애(functional gastrointestinal disorder, FGID)의 생물학적 병태생리는 아직 명확하지 않은 실정이나 최근에 뇌-장관 축(brain-gut axis, BGA) 모델이 각광받고 있다. BGA 모델은 중추신경계(CNS)와 장관신경계(ENS)가 신경계, 신경내분비계, 신경면역계 등으로 밀접하게 연계되어 양방향성으로 항상성을 유지한다는 이론이다. 또한 BGA는 FGID에 대한 항우울제 효과의 이론적 근거를 제공한다. 저자들은 세로토닌 노르에프네프린 재흡수 차단제인 duloxetine이 목 이물감, 우울감을 보이는 환자와 상부 위장관 팽만감, 건강염려증적 불안을 보이는 환자에서 위장관 증상 및 정신의학적 증상에 효과적이었음을 경험하였다. 이에 두 증례보고를 통하여 BGA에 대해서 간략히 검토하고 duloxetine의 효과를 BGA의 측면에서 고찰하였다. 이 두 증례에서 duloxetine의 장관에서 뇌로의 영향(bottom-up regulation)으로는 세로토닌 수용체, 노르에피네프린 수용체 그리고 부신피질자극호르몬방출인자(CRF) 길항효과를 통해서 내장과민성(visceral hypersensitivity) 및 정신의학적 증상을 호전시키고, 뇌에서 장관으로의 영향(top-down regulation)으로는 우울과 불안을 호전시킴으로 위장관 증상에 영향을 미친 것으로 추정해 볼 수 있다.

• 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.

• 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.