scholarly journals Melatonin Regulates the Neurotransmitter Secretion Disorder Induced by Caffeine Through the Microbiota-Gut-Brain Axis in Zebrafish (Danio rerio)

Author(s):  
Zeng Zhang ◽  
Qiannan Peng ◽  
Dongxue Huo ◽  
Shuaiming Jiang ◽  
Chenchen Ma ◽  
...  

Melatonin has been widely used as a “probiotic agent” capable of producing strong neurotransmitter secretion regulatory effects, and the microbiota-gut-brain axis-related studies have also highlighted the role of the gut microbiota in neuromodulation. In the present study, a zebrafish neural hyperactivity model was established using caffeine induction to explore the regulatory effects of melatonin and probiotic on neurotransmitter secretion disorder in zebrafish. Disorders of brain neurotransmitter secretion (dopamine, γ-aminobutyric acid, and 5-hydroxytryptamine) caused by caffeine were improved after interference treatment with melatonin or probiotic. Shotgun metagenomic sequencing demonstrated that the melatonin-treated zebrafish gradually restored their normal intestinal microbiota and metabolic pathways. Germ-free (GF) zebrafish were used to verify the essential role of intestinal microbes in the regulation of neurotransmitter secretion. The results of the neurotransmitter and short-chain fatty acid determination revealed that the effect on the zebrafish in the GF group could not achieve that on the zebrafish in the melatonin group after adding the same dose of melatonin. The present research revealed the potential mode of action of melatonin through the microbiota-gut-brain axis to regulate the disruption of neurotransmitter secretion, supporting the future development of psychotropic drugs targeting the intestinal microbiota.

2019 ◽  
Author(s):  
Qiannan Peng ◽  
Zeng Zhang ◽  
Dongxue Huo ◽  
Shuaiming Jiang ◽  
Chenchen Ma ◽  
...  

Abstract Background : Melatonin has been widely used as a "probiotic agent" capable of producing strong neurotransmitter secretion regulatory effects. In the present study, a zebrafish neural hyperactivity model was established using caffeine induction, and the regulation and mechanism of melatonin and probiotic on zebrafish neurotransmitter secretion disorder were explored. Results : Disorders of brain neurotransmitter secretion caused by caffeine, including that of dopamine (DA), γ-aminobutyric acid (γ-GABA), and 5-hydroxytryptamine (5-HT), were improved after interference treatment with melatonin or the probiotic. Metagenomic sequencing demonstrated that the melatonin-treated zebrafish gradually restored their normal intestinal microbial structure, while probiotic supplementation may restructure a new microbiome. Additionally, supplementation with melatonin significantly regulated intestinal microbial functional features. Based on this activity, we supposed that gut microbes play an essential role in the regulation of neurotransmitter secretion disorder via a process that involves melatonin. Germ-free (GF) zebrafish were used to verify the hypotheses. Validation experiment results revealed that the effect on the zebrafish in the GF group could not achieve that on the zebrafish in the melatonin group after adding the same dose of melatonin, and subsequent real-time PCR and metabolic pathway analysis confirmed the conclusion. Meanwhile, the content of acetic acid and propionic acid in the zebrafish gut decreased after caffeine induction and increased significantly after melatonin treatment. Conclusions : In the present research, we identified the potential mechanism of melatonin regulation of neurotransmitter secretion disorder through the gut-brain axis, laying a foundation for exploring the prevention and treatment of some neuropsychiatric disorders by improving the intestinal microbiota.


Blood ◽  
2015 ◽  
Vol 126 (3) ◽  
pp. 311-318 ◽  
Author(s):  
Veronica E. Manzo ◽  
Ami S. Bhatt

AbstractHumans are now understood to be in complex symbiosis with a diverse ecosystem of microbial organisms, including bacteria, viruses, and fungi. Efforts to characterize the role of these microorganisms, commonly referred as the microbiota, in human health have sought to answer the fundamental questions of what organisms are present, how are they functioning to interact with human cells, and by what mechanism are these interactions occurring. In this review, we describe recent efforts to describe the microbiota in healthy and diseased individuals, summarize the role of various molecular technologies (ranging from 16S ribosomal RNA to shotgun metagenomic sequencing) in enumerating the community structure of the microbiota, and explore known interactions between the microbiota and humans, with a focus on the microbiota’s role in hematopoiesis and hematologic diseases.


2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S160-S161
Author(s):  
D Khusnutdinova ◽  
M Markelova ◽  
M Siniagina ◽  
E Boulygina ◽  
S Abdulkhakov ◽  
...  

Abstract Background Changes in the composition of gut microbiota, and their metabolic pathways, are important factors in the pathogenesis of inflammatory bowel disease (IBD). Many clinical trials have shown that taking probiotics based on Lactobacillus has a positive effect on patients with IBD. However, Lactobacillus should be used more carefully during the active phase of IBD, since some strains can negatively affect the pathogenesis of the disease1,2. The aim of this study was to assess the diversity of Lactobacillus species in the gut microbiome of IBD patients and healthy volunteers. Methods In the study, 62 stool samples from healthy people, 31 from patients with Crohn’s disease (CD), and 34 - ulcerative colitis (UC) in active phase were analyzed. DNA was isolated using the QIAamp Fast DNA Stool Mini Kit (Qiagen, USA) following with shotgun metagenomic sequencing the NextSeq 500 (project #0671-2020-0058). Bioinformatic analysis was performed with the MetaPhlAn2 package. Results An increased relative abundance of Lactobacillus was found in patients with IBD (3.2% ± 6.6% in CD and 1.6% ± 2.8 in UC) compared to healthy individuals (0.3% ± 1.2%, p<0.05). In the control group, Lactobacillus were absent in 41% of samples and 1–5 species were found in 58% of samples. Most CD and UC patients are characterized by the presence of 3 to 5 species of Lactobacillus (38% and 31%, respectively). For 23% of CD patients and 26% of UC patients, 6 to 9 types of Lactobacillus were found. Some patients with IBD have more than 10 different types of Lactobacillus in the gut microbiota (Fig.1). The intestinal microbiota in IBD patients is characterized by an increased abundance of several species: L. salivarius, L. gasseri, L. mucosae, as well as L. casei paracasei in patients with CD and L. vaginalis in patients with UC (Fig.2). Conclusion The composition of the intestinal microbiota of IBD patients differs significantly in terms of Lactobacillus proportion and species diversity. Overabundance of five Lactobacillus species could be associated with the active phase of IBD. References


2019 ◽  
Author(s):  
Alessia Visconti ◽  
Caroline I. Le Roy ◽  
Fabio Rosa ◽  
Niccolo Rossi ◽  
Tiphaine C. Martin ◽  
...  

AbstractThe human gut is inhabited by a complex and metabolically active microbial ecosystem regulating host health. While many studies have focused on the effect of individual microbial taxa, the metabolic potential of the entire gut microbial ecosystem has been largely under-explored. We characterised the gut microbiome of 1,004 twins via whole shotgun metagenomic sequencing (average 39M reads per sample). We observed greater similarity, across unrelated individuals, for functional metabolic pathways (82%) than for taxonomic composition (43%). We conducted a microbiota-wide association study linking both taxonomic information and microbial metabolic pathways with 673 blood and 713 faecal metabolites (Metabolon, Inc.). Metabolic pathways associated with 34% of blood and 95% of faecal metabolites, with over 18,000 significant associations, while species-level results identified less than 3,000 associations, suggesting that coordinated action of multiple taxa is required to affect the metabolome. Finally, we estimated that the microbiome mediated a crosstalk between 71% of faecal and 15% of blood metabolites, highlighting six key species (unclassified Subdoligranulum spp., Faecalibacterium prausnitzii, Roseburia inulinivorans, Methanobrevibacter smithii, Eubacterium rectale, and Akkermansia muciniphila). Because of the large inter-person variability in microbiome composition, our results underline the importance of studying gut microbial metabolic pathways rather than focusing purely on taxonomy to find therapeutic and diagnostic targets.


2020 ◽  
pp. 135-144
Author(s):  
E. Yu. Plotnikova ◽  
Yu. V. Zakharova

Today, there is an explosion of discoveries related to a growing understanding of the role of microbial communities, key species of bacteria, products or metabolites derived from commensals, and in particular the relationship between some of these components and painful conditions in humans. Microbiota plays a fundamental role in the induction, training and functioning of the host’s immune system. In turn, the immune system has evolved significantly as a means of maintaining the host’s symbiotic relations with these very diverse and developing microbes. At optimal performance, this alliance of the immune system and microbiota allows to induce protective reactions to pathogens and maintain regulatory pathways involved in maintaining tolerance to harmless antigens. In this review, we outline the role of the intestinal microbiota in the immune system, starting with initial information supporting further insights into the effects of intestinal microbiota dysbacteriosis on the host’s susceptibility to infection. Probiotics are considered a good form of therapy to control harmful intestinal microorganisms, improve digestion and the absorption of nutrients. The beneficial effects of probiotics have been demonstrated in many diseases. One of the main mechanisms of probiotics is the regulation of the immune response of the host. The article reviews and discusses the regulatory role of probiotics in the “intestine-lungs” system and the immune system of mucous membranes for potential antiviral mechanisms. The unique role of probiotics in modulation of intestinal microbes and establishment of intestinal homeostasis and production of interferon as antiviral mechanism is described. In addition, the regulatory role of probiotics in the system «intestine-lungs» and the immune system of the mucous membranes for potential antiviral mechanisms, including in COVID-19 is considered and discussed. Symbiotic products Bac-Set® Forte and Bac-Set® Cold/Flu are described.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Shengli Ma ◽  
Fan Zhang ◽  
Fengxia Zhou ◽  
Hui Li ◽  
Wenyu Ge ◽  
...  

AbstractCOVID-19 remains a serious emerging global health problem, and little is known about the role of oropharynx commensal microbes in infection susceptibility and severity. Here, we present the oropharyngeal microbiota characteristics identified by shotgun metagenomic sequencing analyses of oropharynx swab specimens from 31 COVID-19 patients, 29 influenza B patients, and 28 healthy controls. Our results revealed a distinct oropharyngeal microbiota composition in the COVID-19 patients, characterized by enrichment of opportunistic pathogens such as Veillonella and Megasphaera and depletion of Pseudopropionibacterium, Rothia, and Streptococcus. Based on the relative abundance of the oropharyngeal microbiome, we built a microbial classifier to distinguish COVID-19 patients from flu patients and healthy controls with an AUC of 0.889, in which Veillonella was identified as the most prominent biomarker for COVID-19 group. Several members of the genus Veillonella, especially Veillonella parvula which was highly enriched in the oropharynx of our COVID-19 patients, were also overrepresented in the BALF of COVID-19 patients, indicating that the oral cavity acts as a natural reservoir for pathogens to induce co-infections in the lungs of COVID-19 patients. We also found the increased ratios of Klebsiella sp., Acinetobacter sp., and Serratia sp. were correlated with both disease severity and elevated systemic inflammation markers (neutrophil–lymphocyte ratio, NLR), suggesting that these oropharynx microbiota alterations may impact COVID-19 severity by influencing the inflammatory response. Moreover, the oropharyngeal microbiome of COVID-19 patients exhibited a significant enrichment in amino acid metabolism and xenobiotic biodegradation and metabolism. In addition, all 26 drug classes of antimicrobial resistance genes were detected in the COVID-19 group, and were significantly enriched in critical cases. In conclusion, we found that oropharyngeal microbiota alterations and functional differences were associated with COVID-19 severity.


2019 ◽  
Vol 110 (6) ◽  
pp. 1404-1415 ◽  
Author(s):  
Angela McCann ◽  
Ian B Jeffery ◽  
Bouchra Ouliass ◽  
Guylaine Ferland ◽  
Xueyen Fu ◽  
...  

ABSTRACT Background Vitamin K has multiple important physiological roles, including blood coagulation and beneficial effects on myelin integrity in the brain. Some intestinal microbes possess the genes to produce vitamin K in the form of menaquinone (MK). MK appears in higher concentration in tissues, such as the brain, particularly MK4, than the dietary form of phylloquinone (PK). Lower PK concentrations have been reported in patients with Alzheimer disease while higher serum PK concentrations have been positively associated with verbal episodic memory. Despite knowledge of the importance of vitamin K for various health parameters, few studies have measured MK concentration and biosynthesis by gut commensals. Objective The aim of the current study was to investigate the relation between genes involved in gut-microbiota derived MK, concentrations of MK isoforms, and cognitive function. Methods Shotgun metagenomic sequencing of the gut microbiome of 74 elderly individuals with different cognitive ability levels was performed. From this, gene counts for microbial MK biosynthesis were determined. Associations between clusters of individuals, grouped based on a similar presence and prevalence of MK biosynthesis genes, and cognitive ability were investigated. Fecal MK concentrations were quantified by HPLC to investigate correlations with subject clusters. Results Separation of subject groups defined by banded quantification of the genetic potential of their microbiome to biosynthesize MK was associated with significant differences in cognitive ability [assessed using the Mini-Mental State Examination (MMSE)]. Three MK isoforms were found to be positively associated with MMSE, along with the identification of key components of the MK pathway that drive this association. Although the causality and direction of these associations remain unknown, these findings justify further studies. Conclusions This study provides evidence that although total concentrations of MK did not covary with cognition, certain MK isoforms synthesized by the gut microbiome, particularly the longer chains, are positively associated with cognition.


2020 ◽  
Author(s):  
Qiannan Peng ◽  
Zeng Zhang ◽  
Dongxue Huo ◽  
Shuaiming Jiang ◽  
Chenchen Ma ◽  
...  

Abstract Background: Melatonin has been widely used as a "probiotic agent" capable of producing strong neurotransmitter secretion regulatory effects. The probiotics related researches also provide the evidence of microbial interactions with the gut-brain axis for mental health. In the present study, a zebrafish neural hyperactivity model was established using caffeine induction, and the regulation and mechanism of melatonin and probiotic on zebrafish neurotransmitter secretion disorder were explored. To further address the challenge that if the gut microbes play an essential role in the regulation of neurotransmitter secretion disorder via a process that involves melatonin, the Germ-free (GF) zebrafish model was used to verify the hypothesis. Results: Disorders of brain neurotransmitter secretion caused by caffeine, including that of dopamine (DA), γ-aminobutyric acid (γ-GABA), and 5-hydroxytryptamine (5-HT), were improved after interference treatment with melatonin or the probiotic. Metagenomic sequencing demonstrated that the melatonin-treated zebrafish gradually restored their normal intestinal microbial structure, while probiotic supplementation may restructure a new microbiome. Additionally, supplementation with melatonin significantly regulated intestinal microbial functional features, which indicated the gut microbiota plays the key role in the function of melatonin. Based on this activity, a Germ-free zebrafish model was applied to verified our hypothesis in the following validation experiment. Validation experiment results revealed that the effect on the zebrafish in the GF group could not achieve that on the zebrafish in the melatonin group after adding the same dose of melatonin, and subsequent real-time PCR and metabolic pathway analysis confirmed the conclusion. Meanwhile, the content of acetic acid and propionic acid in the gut of not-germ-free zebrafish decreased after caffeine induction and increased significantly after melatonin treatment. However, no acetic or propionic acids were found, detected, changed as there are germ-free zebrafish. Conclusions: In the present research, we identified the potential mechanism of melatonin regulation of neurotransmitter secretion disorder through the gut-brain axis, laying a foundation for exploring the prevention and treatment of some neuropsychiatric disorders by improving the intestinal microbiota.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xin Wang ◽  
Gengan Du ◽  
Hong Chen ◽  
Xuejun Zeng ◽  
Bin Liu ◽  
...  

Fuzhuan brick tea (FBT) is a unique post-fermented tea product, naturally co-fermented by microorganisms, and has gained global popularity due to its potential health benefits for humans. Considerable efforts have been made toward elucidating the microbial diversity within FBT, but an understanding of the underlying FBT community interactions and functions remains poorly studied. Consequently, the microbial communities of two types of FBT, originating from Hunan and Shaanxi provinces, were investigated using comparative shotgun metagenomic sequencing and functional annotations. Metagenomic analysis indicated that two communities shared similar taxonomic and functional attributes. Two samples shared 486 genera, in which Pseudomonas contributed most to the abundant functions within the two samples. The carbohydrate active enzyme functions of the communities primarily comprised GH (32.92%), GT (26.8%), CEs (20.43%), and AAs (18.04%). Furthermore, the overall metabolic pathways encoded by the metagenomes were largely associated with carbohydrate and amino acid metabolism, with nine metabolic pathways that were differential between two groups including penicillin and cephalosporin biosynthesis. Significantly, a total of 35 potential probiotics were inferred, with Pseudomonas putida being the most abundant inferred probiotic (80%) within the FBT communities. This study provides new insights into FBT microbial communities on their potential functions and roles in FBT characteristics.


2019 ◽  
Vol 89 (1-2) ◽  
pp. 80-88 ◽  
Author(s):  
Juliana Soares Severo ◽  
Jennifer Beatriz Silva Morais ◽  
Taynáh Emannuelle Coelho de Freitas ◽  
Ana Letícia Pereira Andrade ◽  
Mayara Monte Feitosa ◽  
...  

Abstract. Thyroid hormones play an important role in body homeostasis by facilitating metabolism of lipids and glucose, regulating metabolic adaptations, responding to changes in energy intake, and controlling thermogenesis. Proper metabolism and action of these hormones requires the participation of various nutrients. Among them is zinc, whose interaction with thyroid hormones is complex. It is known to regulate both the synthesis and mechanism of action of these hormones. In the present review, we aim to shed light on the regulatory effects of zinc on thyroid hormones. Scientific evidence shows that zinc plays a key role in the metabolism of thyroid hormones, specifically by regulating deiodinases enzymes activity, thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH) synthesis, as well as by modulating the structures of essential transcription factors involved in the synthesis of thyroid hormones. Serum concentrations of zinc also appear to influence the levels of serum T3, T4 and TSH. In addition, studies have shown that Zinc transporters (ZnTs) are present in the hypothalamus, pituitary and thyroid, but their functions remain unknown. Therefore, it is important to further investigate the roles of zinc in regulation of thyroid hormones metabolism, and their importance in the treatment of several diseases associated with thyroid gland dysfunction.


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