• Biomolecules & Therapeutics
• /
• v.31 no.4
• /
• pp.417-424
• /
• 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
• /
• v.36 no.3
• /
• pp.133-145
• /
• 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
• /
• v.32 no.7
• /
• pp.927-937
• /
• 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
• /
• v.24 no.4
• /
• pp.512-527
• /
• 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
• /
• v.34 no.3
• /
• pp.487-494
• /
• 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.

• Food Science of Animal Resources
• /
• v.43 no.6
• /
• pp.1044-1054
• /
• 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.

• Journal of Life Science
• /
• v.28 no.11
• /
• pp.1386-1395
• /
• 2018

Over recent years, it has become evident that the central nervous system bidirectionally interacts with the gastrointestinal tract along the gut-brain axis. A series of preclinical studies indicate that the gut microbiota can modulate central nervous system function through a multitude of physiological functions. Polyphenols are ubiquitous plant chemicals included in foods such as fruits, vegetables, tea, coffee and wine, and their consumption is directly responsible for beneficial health effects due to antioxidant, anti-inflammatory, antimicrobial, immunomodulatory, anticancer, vasodilating, and prebiotic-like effects. There is increasing evidence that dietary polyphenol can contribute to beneficial effects in neuronal protection acting against oxidative stress and inflammatory injury as well as in cognitive functions. In this paper, we overview the neuroprotective role of dietary polyphenols especially focusing on the neuroinflammation and neurovascular function by interaction with the gut microbiome. Polyphenol metabolites could directly act as neurotransmitters crossing the blood-brain barrier and modulating the cerebrovascular system or indirectly modulating gut microbiota. In addition, evidence suggests that dietary polyphenols are effective in preventing and managing neurological disorders, such as age-related cognitive decline and neurodegeneration, through a multitude of physiological functions. Dietary polyphenols are increasingly envisaged as a potential nutraceuticals in the prevention and treatment of neurological disorders, because they possess the ability to reduce neuroinflammation, to improve memory and cognitive function and to modulate the gut microbiota.

• Clinical Psychopharmacology and Neuroscience
• /
• v.16 no.4
• /
• pp.422-433
• /
• 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.

• Journal of Ginseng Research
• /
• v.47 no.2
• /
• pp.255-264
• /
• 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
• /
• v.33 no.9
• /
• pp.1189-1196
• /
• 2023

This study proposed to demonstrate the neuroprotective effects of heat-killed Levilactobacillus brevis KU15152. Heat-killed L. brevis KU15152 showed antioxidant activity similar to that of Lacticaseibacillus rhamnosus GG, in terms of radical scavenging activity. To evaluate the neuroprotective effects, conditioned medium (CM) obtained by incubating heat-killed bacteria in intestinal cells (HT-29) was used through gut-brain axis. CM from L. brevis KU15152 protected neuroblastoma cells (SH-SY5Y) against H₂O₂-induced oxidative stress. Pretreatment with CM significantly alleviated the morphological changes induced by H₂O₂. Heat-killed L. brevis KU15152 showed an increased brain-derived neurotrophic factor (BDNF) expression in HT-29 cells. L. brevis KU15152-CM remarkably downregulated the Bax/Bcl-2 ratio, while upregulating the expression of BDNF and tyrosine hydroxylase (TH) in SH-SY5Y cells. Furthermore, L. brevis KU15152-CM reduced caspase-3 activity following H₂O₂ treatment. In conclusion, L. brevis KU15152 can be potentially used as food materials to avoid neurodegenerative diseases.