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Gut microbiome and serum metabolome analyses identify Bacteroides fragilis as regulators of serotonin content and PRL secretion in broody geese

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Journal of Integrative Agriculture 2024年第6期23卷 2033-2051页

作者： Yu Zhang Ning Zhou Jia Wu Lina Song Qiang Bao Kaiqi Weng Yang Zhang Wanwipa Vongsangnak Guohong Chen Qi Xu College of Animal Science and Technology Yangzhou UniversityYangzhou 225009China Joint International Research Laboratory of Agriculture&Agri-Product Safety of Ministry of Education Yangzhou UniversityYangzhou 225009China Department of Zoology Faculty of ScienceKasetsart UniversityBangkok 10900Thailand

Broody behavior is regulated by hypothalamic prolactin secretion,which seriously affects egg production in poulty production.Numerous studies have provided evidence that animal behavior is governed by dynamic bidirectional communication between specific gut bacteria and their host via the brain-gut-microbiome axis.However,little research focused on how the gut microbiota influence broody behavior in poultry.In this study,Zhedong white geese in laying and brooding phases were selected.Ten differentially abundant bacteria in cecum were detected between brooding and laying geese through metagenomic analyses and 16S rRNA sequencing(Pserotonin,etc.)in broody geese,which hinted that those tryptophan metabolites might be produced or driven by B.fragilis.Finally,the serum hormone levels were also measured.We found there was a positive correlation between B.fragilis abundance and content of serotonin.Besides,prolactin secreted by the pituitary gland was greater in brooding geese than that in laying geese,which was also highly correlated with B.fragilis abundance.This result implied that B.fragilis could promote the secretion of prolactin by the pituitary gland.Together,the current study findings provided the information on gut microbiota influencing broody behavior,B.fragilis produced or driven more serum serotonin,and stimulated the pituitary gland to secret more prolactin,which potentially offered a new enlightenment for the intervention of broody behavior in poultry.

关键词： geese broody behavior gut microbiota serotonin prolactin

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serotonin syndrome controversies:A need for consensus

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World Journal of Critical Care Medicine 2024年第2期13卷 150-158页

作者： Sanjay Prakash Chetsi S Shah Anurag Prakash Department of Neurology Smt.B.K.Shah Medical Institute and Research CentreSumandeep VidyapeethVadodara 391760GujarātIndia Medicine Parul Institute of Medical Sciences and Research CentreParul University WaghodiaVadodara 391760India

serotonin syndrome(SS)is a drug-induced clinical syndrome resulting from increased serotonergic activity in the central nervous system.Although more than seven decades have passed since the first description of SS,it is still an enigma in terms of terminology,clinical features,etiology,pathophysiology,diagnostic criteria,and therapeutic measures.The majority of SS cases have previously been reported by toxicology or psychiatry centers,particularly in people with mental illness.However,serotonergic medications are used for a variety of conditions other than mental illness.Serotonergic properties have been discovered in several new drugs,including over-the-counter medications.These days,cases are reported in non-toxicology centers,such as perioperative settings,neurology clinics,cardiology settings,gynecology settings,and pediatric clinics.Overdoses or poisonings of serotonergic agents constituted the majority of the cases observed in toxicology or psychiatry centers.Overdose or poisoning of serotonergic drugs is uncommon in other clinical settings.Patients may develop SS at therapeutic dosages.Moreover,these patients may continue to use serotonergic medications even if they develop mild to moderate SS due to several reasons.Thus,the clinical presentation(onset,severity,and clinical features)in such instances may not exactly match what toxicologists or psychiatrists observe in their respective settings.They produce considerable diversity in many aspects of SS.However,other experts discount these new developments in SS.Since SS is a potentially lethal illness,consensus is required on several concerns related to SS.

关键词： serotonin serotonin syndrome serotonin toxicity Selective serotonin reuptake inhibitors Antidepressants Cyproheptadine

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Hemostatic mechanism of Jianpi Yiqi Shexue decoction(健脾益气摄血方) in treatment of immune thrombocytopenia

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Journal of Traditional Chinese Medicine 2024年第3期44卷 537-544页

作者： LI Ruibai CHEN Ke MA Wei ZHANG Yayue HOU Li CHEN Xinyi Department of Oncology and Hemotology Dongzhimen HospitalBeijing University of Chinese Medicine Department of Hemotology Xiyuan HospitalChina Academy of Chinese Medical Sciences

OBJECTIVE: To explore the early hemostatic mechanism of Jianpi Yiqi Shexue decoction(健脾益气摄血方, JYSD) in treating immune thrombocytopathy(ITP), based on the functional homeostasis of brain-intestine axis and blood neurotransmitter METHODS: Non-drug treatment cases: Healthy volunteers were selected as normal control group and compared with patients with dysfunctional uterine bleeding, gastrointestinal tumors with bleeding and ITP, to detect the changes of blood 5-hydroxytryptamine(5-HT), β-endorphin(β-EP), vasoactive intestinal peptide(VIP) and compare the changes of blood neurotransmitters in patients with different disease symptoms. Drug treatment cases: According to the randomized controlled multicenter clinical trial, 272 ITP patients were randomly divided into three groups: treatment group(JYSD) combined group(JYSD + Prednisone) control group(Prednisone). The changes of blood neurotransmitter(5-HT, β-EP, VIP) before and after treatment were detected on the basis of peripheral blood platelet(PLT) and grade score. RESULTS: Non-drug treatment cases: compared with the normal control group, the 5-HT level was higher, and the VIP and β-EP levels were both lower in the ITP group(P < 0.001), and the 5-HT, VIP and β-EP levels in the Gastrointestinal tumors with bleeding group were also lower compared with the normal control group(P < 0.05, 0.001). Drug treatment cases: The PLT grading scores of the combination group and the control group after treatment were lower than that before treatment(P < 0.05, 0.001). The PLT grading score of the 3 groups were compared in pairs after treatment: the combination group was the lowest among the 3 groups, which was better than the treatment group, but no better than the control group(vs the treatment group, P = 0.005, vs the control group, P = 0.709). The statistical results of full analysis set(FAS) and per protocol set(PPS) were consistent. The bleeding symptom scores of the treatment and combination groups began to drop 7 d after treatment, and kept dropping 14 d after treatment un

关键词： beta-endorphin brain-gut axis immune thrombocytopenic purpura serotonin vasoactive intestinal peptide

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Exploring a novel class tryptophan hydroxylase 1 inhibitor derived from Sambucus williamsii Hance for the osteoporosis treatment

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Acupuncture and Herbal Medicine 2024年第1期4卷 102-112页

作者： Yu-Xin Zhu Zi-Ling Tang Lu Lu Zuo-Cheng Qiu Dabo Pan Yang Yu Hui-Hui Xiao Man-Sau Wong State Key Laboratory of Chinese Medicine and Molecular Pharmacology(Incubation) The Hong Kong Polytechnic University Shenzhen Research InstituteShenzhenChina Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine School of Traditional Chinese MedicineJinan UniversityGuangzhouChina Guangdong Provincial Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research College of PharmacyJinan UniversityGuangzhouChina Department of Food Science and Nutrition The Hong Kong Polytechnic UniversityHong KongChina Research Center for Chinese Medicine Innovation The Hong Kong Polytechnic UniversityHong KongChina

Objective:Gut-derived serotonin strongly inhibits bone formation by inhibiting osteoblast proliferation.Our previous study demonstrated that the lignan-rich fraction prepared from Sambucus willimasii Hance,a folk herbal medicine used to treat bone fractures and joint diseases in China,exerted bone-protective effects,and its actions were modulated by suppressing the synthesis of gut-derived serotonin via the inhibition of intestinal tryptophan hydroxylase 1(TPH-1).However,there is no direct evidence for the action of lignans on TPH-1.This study aimed to verify the direct action of lignans on the TPH-1 and its influence on serotonin synthesis and bone properties.Methods:Molecular docking and surface plasmon resonance were performed to determine the affinities of lignans to TPH-1.The cell viability and the protein activity and expression of TPH-1 were measured in RBL2H3 cells.The serum serotonin level and bone mineral density upon lignan treatment in ovariectomized mice were determined.Result:The lignans showed high binding scores and binding affinities to TPH-1,inhibited the activity and protein expression of TPH-1,suppressed the serum serotonin levels in ovariectomized mice as well as promoted bone mineral density.Conclusion:This is the first study to report that lignans are novel TPH-1 inhibitors and that these lignans could be potential agents for the management of serotonin-related diseases,including osteoporosis.

关键词： Lignan Osteoporosis Sambucus williamsii Hance serotonin TPH-1 inhibitor

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serotonin Signaling Modulates Sexual Receptivity of Virgin Female Drosophila

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Neuroscience Bulletin 2022年第11期38卷 1277-1291页

作者： Baoxu Ma Rencong Wang Yaohua Liu Bowen Deng Tao Wang Fengming Wu Chuan Zhou State Key Laboratory of Integrated Management of Pest Insects and Rodents Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100101China Department of Plant Protection Shanxi Agricultural UniversityJinzhong 30801China Chinese Institute for Brain Research Zhongguancun Life Sciences ParkBeijing 102206China Institute of Molecular Physiology Shenzhen Bay LaboratoryShenzhen 518132China

The choice of females to accept or reject male courtship is a critical decision for animal reproduction.serotonin(5-hydroxytryptamine;5-HT)has been found to regulate sexual behavior in many species,but it is unclear how 5-HT and its receptors function to regulate different aspects of sexual behavior.Here we used Drosophila melanogaster as the model animal to investigate how 5-HT and its receptors modulate female sexual receptivity.We found that knockout of tryptophan hydroxylase(Trh),which is involved in the biosynthesis of 5-HT,severely reduced virgin female receptivity without affecting post-mating behaviors.We identified a subset of sexually dimorphic Trh neurons that co-expressed fruitless(fru),in which the activity was correlated with sexual receptivity in females.We also found that 5-HT1A and 5-HT7 receptors regulate virgin female receptivity.Our findings demonstrate how 5-HT functions in sexually dimorphic neurons to promote virgin female receptivity through two of its receptors.

关键词： Female sexual receptivity serotonin 5-HT Fruitless Neurochemical 5-HT receptors Drosophila

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serotonin enrichment of rice endosperm by metabolic engineering

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The Crop Journal 2023年第6期11卷 1943-1948页

作者： Qingqing Yang Yan Tan Ying Ye Dongsheng Zhao Qiaoquan Liu Key Laboratory of Crop Genomics and Molecular Breeding of Jiangsu Province/Zhongshan Biological Breeding Laboratory/Key Laboratory of Plant Functional Genomics of the Ministry of Education College of AgricultureYangzhou UniversityYangzhou 225009JiangsuChina Jiangsu Co-Innovation Center for Modern Production Technology of Grain Crops/Jiangsu Key Laboratory of Crop Genetics and Physiology Yangzhou UniversityYangzhou 225009JiangsuChina

In animals,serotonin is a neurotransmitter and mood regulator.In plants,serotonin functions in energy acquisition,tissue maintenance,delay of senescence,and response to biotic and abiotic stresses.In this study,we examined the effect of serotonin enrichment of rice endosperm on plant growth,endosperm development,and grain quality.To do so,TDCs and T5H were selected as targets for serotonin fortification.Overexpression of TDC1 or TDC3 increased serotonin accumulation relative to overexpression of T5H in rice grain.Transgenic lines of target genes driven by the Gt1 promoter showed better field performance than those driven by the Ubi promoter.Overexpression of T5H showed little effect on plant growth or grain physicochemical quality.In neuronal cell culture assays,serotonin induced neuroprotective action against apoptosis.Breeding of rice cultivars with high serotonin content may be beneficial for health and nutrition.

关键词： Rice endosperm serotonin Metabolic engineering TDCs T5H

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Fecal transplantation can alleviate tic severity in a Tourette syndrome mouse model by modulating intestinal flora and promoting serotonin secretion

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Chinese Medical Journal 2022年第6期135卷 707-713页

作者： Hua Li Yong Wang Changying Zhao Jian Liu Lei Zhang Anyuan Li Department of Gastroenterology Cheeloo Children's HospitalShandong UniversityJinanShandong 250022China Department of Laboratory Medicine School of Stomatology and MedicineFoshan UniversityChancheng DistrictFoshanGuangdong 528000China Jinan Institute of Paediatric Medicine Cheeloo Children's HospitalShandong UniversityJinanShandong 250022China Microbiome-X National Institute of Health Data Science of ChinaCheeloo College of MedicineShandong UniversityJinanShandong 250002China Department of Traditional Chinese Medicine Shandong Provincial HospitalShandong UniversityJinanShandong 250021China

Background:Tourette syndrome(TS)is a neuropsychiatric disorder with onset in childhood that warrants effective therapies.Gut microbiota can affect central physiology and function via the microbiota-gut-brain axis.Therefore,the gut microbiota plays an important role in some mental illnesses.A small clinical trial showed that fecal microbiota transplantation(FMT)may alleviate TS symptoms in children.Herein,FMT effects and mechanisms were explored in a TS mouse model.Methods:TS mice model(TSMO)(n=80)were established with 3,3'-iminodipropionitrile,and 80 mice were used as controls.Mice were grouped into eight groups and were subjected to FMT with feces from children or mice with or without TS,or were given probiotics.Fecal specimens were collected 3 weeks after FMT.16S rRNA sequencing,behavioral observation,and serum serotonin(5-HT)assay were performed.Differences between groups were analyzed using Mann-Whitney U test and Kolmogorov-Smirnov(KS)tests.Results:A total of 18 discriminative microbial signatures(linear discriminant analysis score>3)that varied significantly between TS and healthy mice(CONH)were identified.A significant increase in Turicibacteraceae and Ruminococcaceae in TSMO after FMT was observed(P<0.05).Compared with non-transplanted TSMO,the symptoms of those transplanted with feces from CONH were alleviated(W=336,P=0.046).In the probiotic and FMT experiments,the serum 5-HT levels significantly increased in TSMO that received probiotics(KS=1.423,P=0.035)and in those transplanted with feces from CONH(W=336.5,P=0.046)compared with TSMO without transplantation.Conclusions:This study suggests that FMT may ameliorate TS by promoting 5-HT secretion,and it provides new insights into the underlying mechanisms of FMT as a treatment for TS.

关键词： Tourette syndrome Fecal transplantation Microbiota serotonin

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Regulation of serotonin production by specific microbes from piglet gut

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Journal of Animal Science and Biotechnology 2023年第6期14卷 2539-2553页

作者： Ziyu Liu Yidan Ling Yu Peng Shuibing Han Yuting Ren Yujia Jing Wenlu Fan Yong Su Chunlong Mu Weiyun Zhu Laboratory of Gastrointestinal Microbiology College of Animal Science and TechnologyNanjing Agricultural UniversityNanjingChina. National Center for International Research on Animal Gut Nutrition National Experimental Teaching Demonstration Center of Animal ScienceNanjing Agricultural UniversityNanjingChina. Hubei CAT Biological Technology Co. Ltd.WuhanChina. Department of Biochemistry and Molecular Biology Cumming School of MedicineUniversity of CalgaryCalgaryCanada

Background serotonin is an important signaling molecule that regulates secretory and sensory functions in the gut.Gut microbiota has been demonstrated to affect serotonin synthesis in rodent models.However,how gut microbes regulate intestinal serotonin production in piglets remains vague.To investigate the relationship between microbiota and serotonin specifically in the colon,microbial composition and serotonin concentration were analyzed in ileum-cannulated piglets subjected to antibiotic infusion from the ileum when comparing with saline infusion.Microbes that correlated positively with serotonin production were isolated from piglet colon and were further used to investi-gate the regulation mechanisms on serotonin production in IPEC-J2 and a putative enterochromaffin cell line RIN-14B cells.Results Antibiotic infusion increased quantities of Lactobacillus amylovorus(LA)that positively correlated with increased serotonin concentrations in the colon,while no effects observed for Limosilactobacillus reuteri(LR).To understand how microbes regulate serotonin,representative strains of LA,LR,and Streptococcus alactolyticus(SA,enriched in feces from prior observation)were selected for cell culture studies.Compared to the control group,LA,LR and SA supernatants significantly up-regulated tryptophan hydroxylase 1(TPH1)expression and promoted serotonin production in IPEC-J2 cells,while in RIN-14B cells only LA exerted similar action.To investigate potential mechanisms mediated by microbe-derived molecules,microbial metabolites including lactate,acetate,glutamine,andγ-aminobutyric acid were selected for cell treatment based on computational and metabolite profiling in bacte-rial supernatant.Among these metabolites,acetate upregulated the expression of free fatty acid receptor 3 and TPH1 while downregulated indoleamine 2,3-dioxygenase 1.Similar effects were also recapitulated when treating the cells with AR420626,an agonist targeting free fatty acid receptor 3.Conclusions Overall,these results suggest that Lactobacillus am

关键词： Colon Lactobacillus Microbial metabolites serotonin

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Morinda officinalis oligosaccharides increase serotonin in the brain and ameliorate depression via promoting 5-hydroxytryptophan production in the gut microbiota

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Acta Pharmaceutica Sinica B 2022年第8期12卷 3298-3312页

作者： Zheng-Wei Zhang Chun-Sheng Gao Heng Zhang Jian Yang Ya-Ping Wang Li-Bin Pan Hang Yu Chi-Yu He Hai-Bin Luo Zhen-Xiong Zhao Xin-Bo Zhou Yu-Li Wang Jie Fu Pei Han Yu-Hui Dong Gang Wang Song Li Yan Wang Jian-Dong Jiang Wu Zhong State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences/Peking Union Medical CollegeBeijing 100050China Beijing Institute of Pharmacology and Toxicology Beijing 100000China Beijing Synchrotron Radiation Facility Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China The National Clinical Research Center for Mental Disorders&Beijing Key Laboratory of Mental Disorders Beijing Anding HospitalCapital Medical UniversityBeijing 100088China Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijing 100069China School of Pharmaceutical Sciences Hainan UniversityHainan 570228China National Engineering Research Center for the Emergence Drugs Beijing 100000China

Morinda officinalis oligosaccharides(MOO) are an oral drug approved in China for the treatment of depression in China. However, MOO is hardly absorbed so that their anti-depressant mechanism has not been elucidated. Here, we show that oral MOO acted on tryptophan → 5-hydroxytryptophan(5-HTP) → serotonin(5-HT) metabolic pathway in the gut microbiota. MOO could increase tryptophan hydroxylase levels in the gut microbiota which accelerated 5-HTP production from tryptophan;meanwhile, MOO inhibited 5-hydroxytryptophan decarboxylase activity, thus reduced 5-HT generation,and accumulated 5-HTP. The raised 5-HTP from the gut microbiota was absorbed to the blood, and then passed across the blood-brain barrier to improve 5-HT levels in the brain. Additionally, pentasaccharide,as one of the main components in MOO, exerted the significant anti-depressant effect through a mechanism identical to that of MOO. This study reveals for the first time that MOO can alleviate depression via increasing 5-HTP in the gut microbiota.

关键词： Depression Morinda oficinalis oligosaccharides Gut microbiota Tryptophan hydroxylase 5-Hydroxytryptophan decarboxylase 5-Hydroxytryptophan serotonin Drug metabolism

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Role of serotonin in modulating the development and function of adult-born neurons in the olfactory bulb

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Neural Regeneration Research 2022年第6期17卷 1253-1254页

作者： Natalie Fomin-Thunemann Olga Garaschuk Department of Biomedical Engineering Boston UniversityBostonMAUSA Institute of Physiology Department NeurophysiologyEberhard Karls University of TübingenTübingenGermany

The neuromodulatory transmitter serotonin(5-hydroxytryptamine,5-HT)is synthesized by neurons located in the brainstem,which project more or less densely to the entire central nervous system(Charnay and Leger,2010).serotonin regulates a variety of physiological functions,including food intake,reward,reproduction,sleep-wake cycle,memory,cognition,emotion,and mood(Charnay and Leger,2010).

关键词： serotonin intake modulator

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