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Journal of Sport and Health Science 2023年第1期12卷 36-44页

作者： Kate M.Sales Raylene A.Reimer Faculty of Kinesiology University of CalgaryCalgaryAB T2N 1N4Canada Department of Biochemistry&Molecular Biology Cumming School of MedicineUniversity of CalgaryCalgaryAB T2N 4N1Canada

The gut microbiota refers to the collection of trillions of intestinal microorganisms that modulate central aspects of health and disease through influential effects on host physiology.Recently,a connection has been made between the gut microbiota and exercise.Initial investigations demonstrated the beneficial effects of exercise on the gut microbiota,with cross-sectional studies revealing positive correlations between exerciseassociated states,and healthy gut microbiota and exercise interventions showed post-intervention increases in the abundance of beneficial bacterial taxa.More recent investigations have focused on exploring the reverse relationship:the influence of the gut microbiota on exercise performance.Murine investigations have revealed that certain bacterial taxa may enhance endurance exercise performance by augmenting various aspects of lactate metabolism.Further,Short-chain fatty acids—which modulate metabolism at various organ sites,including within skeletal muscle—have been shown to enhance endurance exercise capacity in mice.This review highlights what is currently known about the connection between the gut microbiota and exercise,with a particular focus on the ergogenic potential of the gut microbiota and how it may be leveraged to enhance endurance exercise performance.

关键词： Exercise performance Gut microbiota Short-chain fatty acids

Relationship Between Short-chain fatty acids and Parkinson's Disease: A Review from Pathology to Clinic

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NEUROSCIENCE BULLETIN 2024年第4期40卷 500-516页

作者： Duan, Wen-Xiang Wang, Fen Liu, Jun-Yi Liu, Chun-Feng Soochow Univ Affiliated Hosp 2 Dept Neurol Suzhou 215004 Peoples R China Soochow Univ Affiliated Hosp 2 Clin Res Ctr Neurol Dis Suzhou 215004 Peoples R China Soochow Univ Jiangsu Key Lab Neuropsychiat Dis Suzhou 215123 Peoples R China Soochow Univ Inst Neurosci Suzhou 215123 Peoples R China Soochow Univ Dushu Lake Hosp Dept Neurol Suzhou 215125 Peoples R China

Parkinson's disease (PD) is a complicated neurodegenerative disease, characterized by the accumulation of & alpha;-synuclein (& alpha;-syn) in Lewy bodies and neurites, and massive loss of midbrain dopamine neurons. Increasing evidence suggests that gut microbiota and microbial metabolites are involved in the development of PD. Among these, Short-chain fatty acids (SCFAs), the most abundant microbial metabolites, have been proven to play a key role in brain-gut communication. In this review, we analyze the role of SCFAs in the pathology of PD from multiple dimensions and summarize the alterations of SCFAs in PD patients as well as their correlation with motor and non-motor symptoms. Future research should focus on further elucidating the role of SCFAs in neuroinflammation, as well as developing novel strategies employing SCFAs and their derivatives to treat PD.

关键词： Parkinson's disease Short-chain fatty acids Microbial metabolites Brain-gut-microbiota axis PROTECTS DOPAMINERGIC-NEURONS BRAIN-BARRIER PERMEABILITY GLUCAGON-LIKE PEPTIDE-1 SODIUM-BUTYRATE ALPHA-SYNUCLEIN GUT MICROBIOTA MONOCARBOXYLATE TRANSPORTERS INDUCED NEUROTOXICITY COLONIC INFLAMMATION METABOLITE BUTYRATE

Supplementing the early diet of broilers with soy protein concentrate can improve intestinal development and enhance short-chain fatty acid-producing microbes and Short-chain fatty acids,especially butyric acid

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Journal of Animal Science and Biotechnology 2023年第1期14卷 278-294页

作者： Qianyun Zhang Shan Zhang Shu Wu Marianne Hjollund Madsen Shourong Shi Poultry Institute Chinese Academy of Agriculture ScienceYangzhou 225125China. TripleA a/s Bjoernkaervej 16DK‑8783 HornsyldDenmark.

Background:Research on nutrition in early-life commonly focuses on the maturation of the intestine because the intestinal system is crucial for ensuring continued growth.To explore the importance of early nutrition regulation in animals,soy protein concentrate(SPC)was added to the early diet of broilers to investigate its effects on amino acid digestibility,intestinal development,especially intestinal microorganisms,and broiler metabolites.A total of 192 oneday-old Arbor Acres(AA)male broilers were randomly assigned to two experimental treatments with 8 replicates of 12 birds.The control group was fed a basal diet(control),and the treatment group was fed a basal diet supplemented with 12%SPC(SPC12)during the first 10 d(starter phase).From d 11 to 21(grower phase)and d 22 to 42(finisher phase),a basal diet was fed to both treatment groups.Results:SPC reduced the pH value and acid-binding capacity of the starter diet(PShort-chain fatty acids(SCFAs)were also increased in the SPC12 group(P<0.05,d 10).Conclusions:In summary,the results showed that supplementing the starter diet of broilers with SPC has a significant effect on the early development of the intestine and the microflora.

关键词： Broiler Caecal microbiota Intestinal development Short-chain fatty acids Soy protein concentrate

Gut microbiota-derived Short-chain fatty acids ameliorate methamphetamine-induced depression-and anxiety-like behaviors in a Sigmar-1 receptor-dependent manner

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Acta Pharmaceutica Sinica B 2023年第12期13卷 4801-4822页

作者： Kaikai Zhang Lijian Chen Jianzheng Yang Jiali Liu Jiahao Li Yi Liu Xiuwen Li Long Chen Clare Hsu Jiahao Zeng Xiaoli Xie Qi Wang Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification School of Forensic MedicineSouthern Medical UniversityGuangzhou 510515China Department of Toxicology School of Public HealthSouthern Medical University(Guangdong Provincial Key Laboratory of Tropical Disease Research)Guangzhou 510515China

Methamphetamine(Meth)abuse can cause serious mental disorders,including anxiety and depression.The gut microbiota is a crucial contributor to maintaining host mental health.Here,we aim to investigate if microbiota participate in Meth-induced mental disorders,and the potential mechanisms involved.Here,15 mg/kg Meth resulted in anxiety-and depression-like behaviors of mice successfully and suppressed the Sigma-1 receptor(SIGMAR1)/BDNF/TRKB pathway in the hippocampus.Mean-while,Meth impaired gut homeostasis by arousing the Toll-like receptor 4(TLR4)-related colonic inflammation,disturbing the gut microbiome and reducing the microbiota-derived Short-chain fatty acids(SCFAs).Moreover,fecal microbiota from Meth-administrated mice mediated the colonic inflam-mation and reproduced anxiety-and depression-like behaviors in recipients.Further,SCFAs supple-mentation optimized Meth-induced microbial dysbiosis,ameliorated colonic inflammation,and repressed anxiety-and depression-like behaviors.Finally,Sigmarl knockout(Sigmar1^(-/-))repressed the BDNF/TRKB pathway and produced similar behavioral phenotypes with Meth exposure,and elim-inated the anti-anxiety and-depression effects of SCFAs.The activation of SIGMAR1 with fluvoxamine attenuated Meth-induced anxiety-and depression-like behaviors.Our findings indicated that gut microbiota-derived SCFAs could optimize gut homeostasis,and ameliorate Meth-induced mental disorders in a SIGMAR1-dependent manner.This study confirms the crucial role of microbiota in Methrelated mental disorders and provides a potential preemptive therapy.

关键词： Methamphetamine Gut microbiota Short-chain fatty acids Sigma-1 receptor Mental disorders Colonic inflammation Intestinal barrier Gut-brain axis

The role of gut microbiota and its metabolites Short-chain fatty acids in food allergy

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Food Science and Human Wellness 2023年第3期12卷 702-710页

作者： Chen Chen Chenglong Liu Ke Zhang Wentong Xue College of Food Science and Nutritional Engineering China Agricultural UniversityBeijing 100083China

Emerging evidence indicated that the increase in food allergy(FA)over the past few decades was associated with the abnormal compositional and metabolic changes of gut microbiota.Gut microbiota played a vital role in maintaining the homeostasis of the immune system and the dysbiosis of gut microbiota promoted the occurrence of FA.Recent research suggested that Short-chain fatty acids(SCFAs),the main metabolites derived from gut microbiota,contributed to FA protection.Herein,we provided a comprehensive review on the relationship between gut microbiota and FA.The multifaceted mechanisms underlymg beneficial effects of gut microbiota composition/metabolites on the regulation of diverse cellular pathways in intestinal epithelial cells,dendritic cells,innate lymphoid cells,T cells,B cells and mast cells in the immune system were discussed systematically.These findings emphasized the positive function of gut microbiota in FA and provided novel ideas for the treatment or prevention of FA in the future.

关键词： Gut microbiota Composition Short-chain fatty acids Immune system Food allergy

Short-chain fatty acids can improve lipid and glucose metabolism independently of the pig gut microbiota

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Journal of Animal Science and Biotechnology 2021年第4期12卷 1414-1427页

作者： Hua Zhou Bing Yu Jing Sun Zuohua Liu Hong Chen Liangpeng Ge Daiwen Chen Key Laboratory of Animal Disease-Resistance Nutrition Chengdu 611130SichuanChina Animal Nutrition Institute Sichuan Agricultural UniversityChengdu 611130SichuanChina Key Laboratory of Pig Industry Sciences Rongchang 402460ChongqingChina Chongqing Academy of Animal Sciences Rongchang 402460ChongqingChina College of Food Science Sichuan Agricultural UniversityYa’an 625014SichuanChina

Background:Previous studies have shown that exogenous Short-chain fatty acids(SCFAs)introduction attenuated the body fat deposition in conventional mice and pigs.However,limited studies have evaluated the effects of exogenously introduced SCFAs on the lipid and glucose metabolism independently of the gut microbiota.This study was to investigate the effects of exogenous introduction of SCFAs on the lipid and glucose metabolism in a germ-free(GF)pig model.Methods:Twelve hysterectomy-derived newborn pigs were reared in six sterile isolators.All pigs were hand-fed with sterile milk powder for 21 d,then the sterile feed was introduced to pigs for another 21 d.In the second 21-d period,six pigs were orally administrated with 25 mL/kg sterile saline per day and considered as the GF group,while the other six pigs were orally administrated with 25 mL/kg SCFAs mixture(acetic,propionic,and butyric acids,45,15,and 11 mmol/L,respectively)per day and regarded as FA group.Results:Orally administrated with SCFAs tended to increase the adiponectin concentration in serum,enhance the CPT-1 activity in longissimus dorsi,and upregulate the ANGPTL4 mRNA expression level in colon(Pfatty acids was most significantly promoted(P<0.05)by oral administration of SCFAs.Conclusions:Exogenous introduction of SCFAs might attenuate the fat deposition and to some extent improve the

关键词： Germ-free Glucose metabolism Lipid metabolism Pig model Short-chain fatty acids

Vitamin A deficiency suppresses CEACAM1 to impair colonic epithelial barrier function via downregulating microbial-derived Short-chain fatty acids

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Genes & Diseases 2024年第2期11卷 1066-1081页

作者： Junyan Yan Lu Xiao Di Feng Baolin Chen Ting Yang Bei Tong Ruifang Luo Yuting Wang Jie Chen Children Nutrition Research Center Children's Hospital of Chongqing Medical UniversityChongqing Key Laboratory of Child Nutrition and HealthMinistry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChongqing 401122China Department of Gastroenterology Children's Hospital of Chongqing Medical UniversityChongqing 401122China

Vitamin A (VA) plays an essential role in modulating both the gut microbiota and gut barrier function.Short-chain fatty acids (SCFAs),as metabolites of the gut microbiota,protect the physiological intestinal barrier;however,they are compromised when VA is deficient.Thus,there is an urgent need to understand how and which SCFAs modulate colonic epithelial barrier integrity in VA deficiency (VAD).Herein,compared with normal VA rats (VAN),at the beginning of pregnancy,we confirmed that the colonic desmosome junction was impaired in the VAD group,and the amounts of acetate,propionate,and butyrate declined because of the decreased abundance of SCFA-producing bacteria (Romboutsia ,Collinsella ,and Allobaculum ).The differentially expressed genes correlated with the gut barrier and the histone deacetylase complex between the VAD and VAN groups were enriched by RNA sequencing.In the VAD group,the expression levels of colonic CEA cell adhesion molecule 1 (CEACAM1) were down-regulated,and the levels of histone deacetylase 1 (HDAC1) and HDAC3 were up-regulated.Intriguingly,the above changes in the VAD groups were rescued by VA supplementation in the early postnatal period.Further study indicated that in Caco-2 cells,butyrate treatment significantly repressed the enrichment of HDAC3 on the promoter of the CEACAM1 gene to induce its expression.Our findings support that butyrate intervention can alleviate the impairment of colonic barrier function caused by VAD,and timely postnatal VA intervention may reverse the damage caused by VAD on gut barrier integrity during pregnancy.

关键词： CEACAM1 Colonic epithelial barrier HDAC3 Short-chain fatty acids Vitamin A deficiency

Effects of common prebiotics on iron status and production of colonic Short-chain fatty acids in anemic rats

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Food Science and Human Wellness 2021年第3期10卷 327-334页

作者： Fan Zhang Ken K.L.Yung Chi KongYeung Division of Science and Technology BNU-HKBU United International CollegeZhuhaiGuangdongChina Department of Biology Hong Kong Baptist UniversityHong KongChina Animal Science Department California Polytechnic State UniversitySan Luis ObispoCaliforniaUSA

Prebiotics may enhance iron absorption,and one plausible mechanism involves the production of shortchain fatty acids(SCFA)in the colon by intestinal microflora.The objectives of this study were to determine the effects of common commercially-available prebiotics including fructooligosaccharide(FOS),inulin,FOS-inulin mixture,galactooligosaccharide(GOS),and lactulose on the iron status of anemic rats,and to monitor changes in the production of colonic SCFA.Anemic Sprague-Dawley rats receiving a lowiron diet(12μg Fe/g diet)were supplemented with or without prebiotics(5%m/V in drinking water)for 5 weeks.Hemoglobin concentration in rats supplemented with GOS after 3 weeks(4.3 g/dL)was significantly higher than rats without supplementation(3.7 g/dL),while FOS also significantly increased hemoglobin concentration after 4 weeks(4.1 g/dL vs.3.7 g/dL).All other prebiotics showed no effects.Anemic rats showed lower overall SCFA production in the colon than normal rats,and only FOS signifi cantly increased the production of the three main SCFA(acetic acid,propionic acid and isobutyric acid)identifi ed in anemic rats,with other prebiotics showing no noticeable trends.Our results suggest that GOS and FOS may slightly improve iron status of anemic rats,but the role of SCFA in the colon is not clear.

关键词： Iron Non-digestible oligosaccharides Short-chain fatty acids Prebiotics Rat

Complex regulatory effects of gut microbial Short-chain fatty acids on immune tolerance and autoimmunity

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Cellular & Molecular Immunology 2023年第4期20卷 341-350页

作者： Chang H.Kim Department of Pathology University of Michigan School of MedicineAnn ArborMI48109USA Mary H.Weiser Food Allergy Center Center for Gastrointestinal Researchand Rogel Center for Can

Immune tolerance deletes or suppresses autoreactive lymphocytes and is established at multiple levels during the development,activation and effector phases of T and B cells.These mechanisms are cell-intrinsically programmed and critical in preventing autoimmune diseases.We have witnessed the existence of another type of immune tolerance mechanism that is shaped by lifestyle choices,such as diet,microbiome and microbial metabolites.Short-chain fatty acids(SCFAs)are the most abundant microbial metabolites in the colonic lumen and are mainly produced by the microbial fermentation of prebiotics,such as dietary fiber.This review focuses on the preventive and immunomodulatory effects of SCFAs on autoimmunity.The tissue-and disease-specific effects of dietary fiber,SCFAs and SCFA-producing microbes on major types of autoimmune diseases,including type I diabetes,multiple sclerosis,rheumatoid arthritis and lupus,are discussed.Additionally,their key regulatory mechanisms for lymphocyte development,tissue barrier function,host metabolism,immunity,autoantibody production,and inflammatory effector and regulatory lymphocytes are discussed.The shared and differential effects of SCFAs on different types and stages of autoimmune diseases are discussed.

关键词： Short-chain fatty acids Immune tolerance Diabetes mellitus Rheumatoid arthritis Lupus Multiple sclerosis

Expression and clinical significance of Short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy

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World Journal of Hepatology 2024年第4期16卷 601-611页

作者： Shuai-Jun Ren Jia-Ting Feng Ting Xiang Cai-Lian Liao Yu-Ping Zhou Rong-Rong Xuan Department of Obstetrics and Gynecology The First Affiliated Hospital of Ningbo UniversityNingbo 315100Zhejiang ProvinceChina Health Science Center Ningbo UniversityNingbo 315211Zhejiang ProvinceChina Department of Gastroenterology The First Affiliated Hospital of Ningbo UniversityNingbo 315211Zhejiang ProvinceChina Institute of Digestive Disease Ningbo UniversityNingbo 315020Zhejiang ProvinceChina

BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy.Short-chain fatty acids(SCFAs),prominent metabolites of the gut microbiota,have significant connections with various pregnancy complications,and some SCFAs hold potential for treating such complications.However,the metabolic profile of SCFAs in patients with ICP remains unclear.AIM To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings.METHODS Maternal serum and cord blood samples were collected from both patients with ICP(ICP group)and normal pregnant women(NP group).Targeted metabolomics was used to assess the SCFA levels in these samples.RESULTS Significant differences in maternal SCFAs were observed between the ICP and NP groups.Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group,mirroring the pattern seen in maternal serum.Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs[r(Pearson)=0.88,P=7.93e-95].In both maternal serum and cord blood,acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups(variable importance for the projection>1).Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP,with caproic acid exhibiting the highest diagnostic efficacy(area under the curve=0.97).CONCLUSION Compared with the NP group,significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group,although they displayed distinct patterns of change.Furthermore,the SCFA levels in maternal serum and cord blood were significantly positively correlated.Notably,certain maternal serum SCFAs,specifically caproic and acetic acids,demonstrated excellent diagnostic efficiency for ICP.

关键词： Intrahepatic cholestasis of pregnancy Short-chain fatty acids Maternal serum Cord blood Caproic acid