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25 pages, 13391 KiB

Open AccessArticle

Lactobacillus plantarum CCFM405 against Rotenone-Induced Parkinson’s Disease Mice via Regulating Gut Microbiota and Branched-Chain Amino Acids Biosynthesis

by Chuanqi Chu, Leilei Yu, Yiwen Li, Hang Guo, Qixiao Zhai, Wei Chen and Fengwei Tian

Nutrients 2023, 15(7), 1737; https://doi.org/10.3390/nu15071737 - 01 Apr 2023

Cited by 9 | Viewed by 2648

Abstract

Recent studies have demonstrated that disturbances in the gut microbiota and microbiota -derived metabolites contribute to the pathogenesis of Parkinson’s disease (PD), suggesting that probiotic treatments that restore them may delay disease progression. This study aimed to examine the attenuating efficacy of L. [...] Read more.

Recent studies have demonstrated that disturbances in the gut microbiota and microbiota -derived metabolites contribute to the pathogenesis of Parkinson’s disease (PD), suggesting that probiotic treatments that restore them may delay disease progression. This study aimed to examine the attenuating efficacy of L. plantarum CCFM405 and the potential mechanisms in mice with rotenone-induced PD. Our results indicate that L. plantarum CCFM405 ameliorated rotenone-induced motor deficits and constipation, decreased dopaminergic neuronal death, reduced intestinal inflammation and neuroinflammation, and raised dopamine levels, 5-HT, and associated metabolites in the striatal region of the brain in mice with PD. Sequencing of 16S rRNA from fecal microbiota revealed that L. plantarum CCFM405 normalized the gut bacterial composition in mice with PD, as evidenced by the increased relative abundance of the following genus, Bifidobacterium, Turicibacter, and Faecalibaculum, and decreased relative abundance of Alistipes, Bilophila, Akkermansia, and Escherichia-Shigella. The PICRUSt-predicted gut microbiota function revealed that L. plantarum CCFM405 enhanced the biosynthesis of amino acid pathways, particularly valine, leucine, and isoleucine (branched-chain amino acids, BCAAs). A non-metabolomic analysis of the serum and feces showed that L. plantarum CCFM405 markedly increased the levels of BCAAs. Pathway enrichment analysis based on the KEGG database further suggested that L. plantarum CCFM405 supplementation can promote BCAAs biosynthesis. Collectively, L. plantarum CCFM405 can help to prevent rotenone-induced PD by modulating the gut microbiota–metabolite axis. BCAAs may play a dominant role in L. plantarum CCFM405-associated neuroprotection in PD mice. This probiotic could be utilized as a potential food supplement in the management of PD. Full article

(This article belongs to the Special Issue Nutritional Strategies to Assist in Alleviating Psychiatric and Neurological Disorders through the Gut-Brain Axis)

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22 pages, 4699 KiB

Open AccessArticle

Effects of a Synbiotic on Plasma Immune Activity Markers and Short-Chain Fatty Acids in Children and Adults with ADHD—A Randomized Controlled Trial

by Liu L. Yang, Miranda Stiernborg, Elin Skott, Jingjing Xu, Yujiao Wu, Rikard Landberg, Samsul Arefin, Karolina Kublickiene, Vincent Millischer, Ida A. K. Nilsson, Martin Schalling, MaiBritt Giacobini and Catharina Lavebratt

Nutrients 2023, 15(5), 1293; https://doi.org/10.3390/nu15051293 - 06 Mar 2023

Cited by 4 | Viewed by 3271

Abstract

Synbiotic 2000, a pre + probiotic, reduced comorbid autistic traits and emotion dysregulation in attention deficit hyperactivity disorder (ADHD) patients. Immune activity and bacteria-derived short-chain fatty acids (SCFAs) are microbiota–gut–brain axis mediators. The aim was to investigate Synbiotic 2000 effects on plasma levels [...] Read more.

Synbiotic 2000, a pre + probiotic, reduced comorbid autistic traits and emotion dysregulation in attention deficit hyperactivity disorder (ADHD) patients. Immune activity and bacteria-derived short-chain fatty acids (SCFAs) are microbiota–gut–brain axis mediators. The aim was to investigate Synbiotic 2000 effects on plasma levels of immune activity markers and SCFAs in children and adults with ADHD. ADHD patients (n = 182) completed the 9-week intervention with Synbiotic 2000 or placebo and 156 provided blood samples. Healthy adult controls (n = 57) provided baseline samples. At baseline, adults with ADHD had higher pro-inflammatory sICAM-1 and sVCAM-1 and lower SCFA levels than controls. Children with ADHD had higher baseline sICAM-1, sVCAM-1, IL-12/IL-23p40, IL-2Rα, and lower formic, acetic, and propionic acid levels than adults with ADHD. sICAM-1, sVCAM-1, and propionic acid levels were more abnormal in children on medication. Synbiotic 2000, compared to placebo, reduced IL-12/IL-23p40 and sICAM-1 and increased propionic acid levels in children on medication. SCFAs correlated negatively with sICAM-1 and sVCAM-1. Preliminary human aortic smooth-muscle-cell experiments indicated that SCFAs protected against IL-1β-induced ICAM-1 expression. These findings suggest that treatment with Synbiotic 2000 reduces IL12/IL-23p40 and sICAM-1 and increases propionic acid levels in children with ADHD. Propionic acid, together with formic and acetic acid, may contribute to the lowering of the higher-than-normal sICAM-1 levels. Full article

(This article belongs to the Special Issue Nutritional Strategies to Assist in Alleviating Psychiatric and Neurological Disorders through the Gut-Brain Axis)

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14 pages, 3459 KiB

Open AccessArticle

Indole Acetic Acid Exerts Anti-Depressive Effects on an Animal Model of Chronic Mild Stress

by Ying Chen, Peijun Tian, Zheng Wang, Ruili Pan, Kexin Shang, Gang Wang, Jianxin Zhao and Wei Chen

Nutrients 2022, 14(23), 5019; https://doi.org/10.3390/nu14235019 - 25 Nov 2022

Cited by 14 | Viewed by 2604

Abstract

Indole acetic acid (IAA), an intestinal bacteria-derived tryptophan metabolite, has been detected at abnormal concentrations in the cerebrospinal fluid and urine of depressed individuals. The effects of such altered IAA concentrations on mood regulation are not known. A mouse model of unpredictable chronic [...] Read more.

Indole acetic acid (IAA), an intestinal bacteria-derived tryptophan metabolite, has been detected at abnormal concentrations in the cerebrospinal fluid and urine of depressed individuals. The effects of such altered IAA concentrations on mood regulation are not known. A mouse model of unpredictable chronic mild stress (UCMS) was used to assess the effects of IAA administration (50 mg/kg). Treatment with IAA for 5 weeks attenuated depression and anxiety-like behaviours, improved hypothalamus–pituitary–adrenal axis dysfunction and increased brain-derived neurotrophic factor expression. IAA supplementation also enhanced the serotonin pathway in the brain and gut. UCMS caused an imbalance of microbial indole metabolites in the colon, whereas IAA treatment reversed this. However, IAA intake did not affect the concentrations of indoles in the brain. Intestinal bacteria in different sections of the gut were altered by IAA treatment, with the colon showing more changes than other segments. The gut microbiome in the colon had increased proportions of Ruminococcaceae UCG013, Ruminiclostridium 6, Prevotella, Alloprevotella and Bacteroides species, which can produce short-chain fatty acids and indole derivatives. Cumulatively, our study highlights the potential of IAA treatment to alleviate mood disorders and offers a theoretical basis for understanding the antidepressant effects of IAA. Full article

(This article belongs to the Special Issue Nutritional Strategies to Assist in Alleviating Psychiatric and Neurological Disorders through the Gut-Brain Axis)

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17 pages, 5024 KiB

Open AccessArticle

Neurotrophic Role of the Next-Generation Probiotic Strain L. lactis MG1363-pMG36e-GLP-1 on Parkinson’s Disease via Inhibiting Ferroptosis

by Mengyun Yue, Jing Wei, Wenjie Chen, Daojun Hong, Tingtao Chen and Xin Fang

Nutrients 2022, 14(22), 4886; https://doi.org/10.3390/nu14224886 - 18 Nov 2022

Cited by 14 | Viewed by 2259

Abstract

Parkinson’s disease (PD) is a neurodegenerative disease (NDD) with high and ongoing morbidity, bringing heavy burdens to PD patients seriously. Finding neurotrophic drugs still remains vital due to the limited drug spectrum available currently. Substantial evidence suggests that glucagon-like peptide 1 (GLP-1) exerts [...] Read more.

Parkinson’s disease (PD) is a neurodegenerative disease (NDD) with high and ongoing morbidity, bringing heavy burdens to PD patients seriously. Finding neurotrophic drugs still remains vital due to the limited drug spectrum available currently. Substantial evidence suggests that glucagon-like peptide 1 (GLP-1) exerts neuroprotection on PD, yet the short-lived biological activity markedly hindered its application. Herein, we investigated the neurotrophic role of the next-generation probiotic strain L. lactis MG1363-pMG36e-GLP-1 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice and elucidated the mechanisms. Our data suggested that L. lactis MG1363-pMG36e-GLP-1 markedly enhanced motor deficits induced by MPTP via rescuing dopaminergic (DAergic) neurodegeneration in substantia nigra (SN). We found that L. lactis MG1363-pMG36e-GLP-1 exerts neurotrophic effects via activating the Keap1/Nrf2/GPX4 signalling pathway to down-regulate ACSL4 and up-regulate FSP1 to suppress ferroptosis. Additionally, the decreased oxidative stress levels via suppressing generations of ROS and MDA supported our findings. Lastly, we identified that the L. lactis MG1363-pMG36e-GLP-1 administration reversed dysbiosis in PD mice by increasing Akkermansia, Oscillospira, and Sutterella at the genus level. These results indicated that the neurotrophic effects of the next-generation probiotics L. lactis MG1363-pMG36e-GLP-1 against MPTP-induced Parkinsonism are mediated by modulating oxidative stress, inhibiting ferroptosis, and redressing dysbiosis. Full article

(This article belongs to the Special Issue Nutritional Strategies to Assist in Alleviating Psychiatric and Neurological Disorders through the Gut-Brain Axis)

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21 pages, 12003 KiB

Open AccessArticle

Neuroprotective Effects of Bifidobacterium breve CCFM1067 in MPTP-Induced Mouse Models of Parkinson’s Disease

by Tiantian Li, Chuanqi Chu, Leilei Yu, Qixiao Zhai, Shunhe Wang, Jianxin Zhao, Hao Zhang, Wei Chen and Fengwei Tian

Nutrients 2022, 14(21), 4678; https://doi.org/10.3390/nu14214678 - 04 Nov 2022

Cited by 20 | Viewed by 3097

Abstract

There is mounting evidence that the microbiota–gut–brain axis (MGBA) is critical in the pathogenesis and progression of Parkinson’s disease (PD), suggesting that probiotic therapy restoring gut microecology may slow down disease progression. In this study, we examined the disease-alleviating effects of Bifidobacterium breve [...] Read more.

There is mounting evidence that the microbiota–gut–brain axis (MGBA) is critical in the pathogenesis and progression of Parkinson’s disease (PD), suggesting that probiotic therapy restoring gut microecology may slow down disease progression. In this study, we examined the disease-alleviating effects of Bifidobacterium breve CCFM1067, orally administered for 5 weeks in a PD mouse model. Our study shows that supplementation with the probiotic B. breve CCFM1067 protected dopaminergic neurons and suppressed glial cell hyperactivation and neuroinflammation in PD mice. In addition, the antioxidant capacity of the central nervous system was enhanced and oxidative stress was alleviated. Moreover, B. breve CCFM1067 protected the blood–brain and intestinal barriers from damage in the MPTP-induced mouse model. The results of fecal microbiota analysis showed that B. breve CCFM1067 intervention could act on the MPTP-induced microecological imbalance in the intestinal microbiota, suppressing the number of pathogenic bacteria (Escherichia-Shigella) while increasing the number of beneficial bacteria (Bifidobacterium and Akkermansia) in PD mice. In addition, the increase in short chain fatty acids (acetic and butyric acids) may explain the anti-inflammatory action of B. breve CCFM1067 in the gut or brain of the MPTP-induced PD mouse model. In conclusion, we demonstrated that the probiotic B. breve CCFM1067, which can prevent or treat PD by modulating the gut–brain axis, can be utilized as a possible new oral supplement for PD therapy. Full article

(This article belongs to the Special Issue Nutritional Strategies to Assist in Alleviating Psychiatric and Neurological Disorders through the Gut-Brain Axis)

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15 pages, 1980 KiB

Open AccessArticle

Bifidobacterium longum CCFM1077 Ameliorated Neurotransmitter Disorder and Neuroinflammation Closely Linked to Regulation in the Kynurenine Pathway of Autistic-like Rats

by Qingmin Kong, Qian Chen, Xuhua Mao, Gang Wang, Jianxin Zhao, Hao Zhang and Wei Chen

Nutrients 2022, 14(8), 1615; https://doi.org/10.3390/nu14081615 - 13 Apr 2022

Cited by 14 | Viewed by 3011

Abstract

The kynurenine pathway (KP) is abnormal in autistic patients and model animals. According to studies on the brain–gut axis, probiotics can help ameliorate the metabolic abnormalities of the KP in patients and model animals with neurological diseases. This study was aimed at evaluating [...] Read more.

The kynurenine pathway (KP) is abnormal in autistic patients and model animals. According to studies on the brain–gut axis, probiotics can help ameliorate the metabolic abnormalities of the KP in patients and model animals with neurological diseases. This study was aimed at evaluating the ability of Bifidobacterium longum (B. longum) CCFM077 to enhance the gut microbiome and KP metabolism and regulate the neurotransmitter levels and neuroinflammation of autistic rats. The KP metabolism of autistic rats was significantly disordered and significantly related to the regulation of neurotransmitter (excitation and inhibition) and neuroglia states. B. longum CCFM1077 could effectively alleviate autistic-like behaviours (repetitive stereotyped behaviour, learning and memory ability, and despair mood) and regulate the KP metabolism in the periphery system (gut and blood) and brain. In particular, B. longum CCFM1077 could significant regulate the quinolinic acid (QUIN) level in the brain and markedly regulate glutamic acid (Glu) and Glu/γ-aminobutyric acid (GABA) levels in the brain while alleviating microglia activity in the cerebellum. Through a correlation analysis, the QUIN level in the brain was strongly related with autistic-like behaviours and neurotransmitter levels (GABA and Glu). The QUIN level may thus be a potential therapeutic marker for treating autism through the intestinal and neural pathways. Full article

(This article belongs to the Special Issue Nutritional Strategies to Assist in Alleviating Psychiatric and Neurological Disorders through the Gut-Brain Axis)

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Review

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16 pages, 2566 KiB

Open AccessEditor’s ChoiceReview

Gut-Microbiota, and Multiple Sclerosis: Background, Evidence, and Perspectives

by Clelia Altieri, Barbara Speranza, Maria Rosaria Corbo, Milena Sinigaglia and Antonio Bevilacqua

Nutrients 2023, 15(4), 942; https://doi.org/10.3390/nu15040942 - 14 Feb 2023

Cited by 9 | Viewed by 3187

Abstract

Many scientific studies reveal a significant connection between human intestinal microbiota, eating habits, and the development of chronic-degenerative diseases; therefore, alterations in the composition and function of the microbiota may be accompanied by different chronic inflammatory mechanisms. Multiple sclerosis (MS) is an inflammatory [...] Read more.

Many scientific studies reveal a significant connection between human intestinal microbiota, eating habits, and the development of chronic-degenerative diseases; therefore, alterations in the composition and function of the microbiota may be accompanied by different chronic inflammatory mechanisms. Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS), in which autoreactive immune cells attack the myelin sheaths of the neurons. The purpose of this paper was to describe the main changes that occur in the gut microbiota of MS patients, with a focus on both microbiota and its implications for health and disease, as well as the variables that influence it. Another point stressed by this paper is the role of microbiota as a triggering factor to modulate the responses of the innate and adaptive immune systems, both in the intestine and in the brain. In addition, a comprehensive overview of the taxa modified by the disease is presented, with some points on microbiota modulation as a therapeutic approach for MS. Finally, the significance of gastro-intestinal pains (indirectly related to dysbiosis) was assessed using a case study (questionnaire for MS patients), as was the willingness of MS patients to modulate gut microbiota with probiotics. Full article

(This article belongs to the Special Issue Nutritional Strategies to Assist in Alleviating Psychiatric and Neurological Disorders through the Gut-Brain Axis)

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26 pages, 687 KiB

Open AccessReview

Role of Short Chain Fatty Acids in Epilepsy and Potential Benefits of Probiotics and Prebiotics: Targeting “Health” of Epileptic Patients

by Soomin Kim, Siyeon Park, Tae Gyu Choi and Sung Soo Kim

Nutrients 2022, 14(14), 2982; https://doi.org/10.3390/nu14142982 - 21 Jul 2022

Cited by 9 | Viewed by 4513

Abstract

The WHO’s definition of health transcends the mere absence of disease, emphasizing physical, mental, and social well-being. As this perspective is being increasingly applied to the management of chronic diseases, research on gut microbiota (GM) is surging, with a focus on its potential [...] Read more.

The WHO’s definition of health transcends the mere absence of disease, emphasizing physical, mental, and social well-being. As this perspective is being increasingly applied to the management of chronic diseases, research on gut microbiota (GM) is surging, with a focus on its potential for persistent and noninvasive dietary therapeutics. In patients with epilepsy (PWE), a chronic lack of seizure control along with often neglected psychiatric comorbidities greatly disrupt the quality of life. Evidence shows that GM-derived short chain fatty acids (SCFAs) may impact seizure susceptibility through modulating (1) excitatory/inhibitory neurotransmitters, (2) oxidative stress and neuroinflammation, and (3) psychosocial stress. These functions are also connected to shared pathologies of epilepsy and its two most common psychiatric consequences: depression and anxiety. As the enhancement of SCFA production is enabled through direct administration, as well as probiotics and prebiotics, related dietary treatments may exert antiseizure effects. This paper explores the potential roles of SCFAs in the context of seizure control and its mental comorbidities, while analyzing existing studies on the effects of pro/prebiotics on epilepsy. Based on currently available data, this study aims to interpret the role of SCFAs in epileptic treatment, extending beyond the absence of seizures to target the health of PWE. Full article

(This article belongs to the Special Issue Nutritional Strategies to Assist in Alleviating Psychiatric and Neurological Disorders through the Gut-Brain Axis)

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