【摘要】酪酸梭菌作为一种重要的产丁酸肠道共生菌和益生菌，在维持肠道稳态和调节宿主生理功能中发挥关键作用。近年来，越来越多的证据表明，酪酸梭菌通过其代谢产物丁酸介导的肠-脑轴双向通讯，对中枢神经系统功能产生深远影响。丁酸作为短链脂肪酸的核心成员，不仅为肠上皮细胞提供能量来源，还可通过抑制组蛋白去乙酰化酶、激活G蛋白偶联受体及调节免疫代谢等多重机制，调控神经炎症、氧化应激、细胞凋亡及血脑屏障完整性。本文系统综述了酪酸梭菌的生物学特性、丁酸的合成代谢与信号转导机制，阐述了酪酸梭菌及其代谢产物丁酸在阿尔茨海默病、帕金森病、抑郁症、自闭症谱系障碍等神经系统疾病中的保护作用及潜在分子机制。

【关键词】酪酸梭菌；丁酸；肠-脑轴；神经保护；肠道基石菌

1 引言

神经系统疾病如阿尔茨海默病（AD）、帕金森病（PD）、抑郁症及自闭症谱系障碍（ASD）等，已成为全球主要致残和致死原因之一[1, 2]。然而，现有治疗手段主要集中于对症处理，难以逆转或延缓疾病进展，且长期使用常伴随明显不良反应[3, 4]。因此，探索基于新机制、能够干预疾病早期进程的治疗策略具有重要的科学意义与临床价值。

肠道微生物群作为人体最庞大且最复杂的微生态系统，其基因编码容量远超宿主基因组，在维持宿主代谢、免疫及神经内分泌稳态中发挥不可替代的作用[5, 6]。近年来的突破性研究表明，肠道菌群不仅局限于局部肠道功能的调节，更通过免疫、神经及内分泌等多重通路与中枢神经系统建立双向通讯，构成“微生物-肠-脑轴”[7, 8]。

在众多肠道微生物代谢产物中，短链脂肪酸（SCFAs）尤其引人注目。SCFAs是肠道菌群发酵膳食纤维的主要终产物，其中丁酸（又称酪酸）又因独特的生物学功能而备受关注[9, 10]。丁酸不仅为结肠上皮细胞提供能量需求，更作为一种重要的信号分子，通过抑制组蛋白去乙酰化酶（HDACs）和激活游离脂肪酸受体等途径，广泛参与宿主能量代谢、免疫调节及神经功能的调控[11, 12]。

酪酸梭菌（又称丁酸梭菌）是一种革兰阳性、严格厌氧、产芽孢的丁酸产生菌，被誉为肠道健康的基石菌，该菌已在中国、日本及韩国被广泛用作益生菌制剂，用于预防和治疗抗生素相关性腹泻等胃肠道疾病[13, 14]。近年来，酪酸梭菌因其卓越的丁酸生产能力及多靶点调节特性，在神经系统疾病领域的潜在应用价值日益凸显。

本文旨在系统综述酪酸梭菌及其代谢产物丁酸在神经系统功能调控中的作用及分子机制，重点关注其在神经退行性疾病、精神障碍及神经发育疾病中的保护效应。

2 酪酸梭菌与丁酸的生物学基础

2.1 酪酸梭菌的生物学特性

酪酸梭菌属于梭菌属，是专性厌氧、产芽孢的革兰阳性杆菌。其芽孢结构赋予该菌极强的环境耐受性，可在强酸及高温等极端条件下存活，这使其在口服给药后能够有效到达结肠并定植[15]。该菌通过发酵宿主难以消化的膳食纤维产生丁酸等，其丁酸合成主要通过丁酸激酶途径完成[16]。酪酸梭菌作为益生菌使用已有数十年历史，其安全性和有效性得到了广泛验证[14]。

2.2 丁酸的合成、转运与代谢

丁酸在结肠内由酪酸梭菌等产丁酸菌发酵产生，其中大部分丁酸被结肠细胞通过β-氧化代谢利用，为肠上皮提供主要能量来源，未被代谢的丁酸则通过门静脉进入体循环[17, 18]。

丁酸跨细胞膜的转运主要通过两种机制：一是依赖pH的单价羧酸转运体MCT1；二是钠依赖性单价羧酸转运体SMCT1[19]。MCT1在脑微血管内皮细胞及神经细胞中均有表达，为丁酸直接作用于中枢神经系统提供了结构基础[20]。放射性标记实验证实丁酸能够通过血脑屏障进入脑实质[21]。

2.3 丁酸的受体与信号通路

丁酸的生物学效应主要通过三条信号通路介导：

（1）HDAC抑制作用：丁酸是最早被发现的天然HDAC抑制剂之一，优先抑制I类、IIa类HDACs[22]。丁酸通过抑制HDAC活性导致组蛋白及非组蛋白高乙酰化，进而调控基因转录。在巨噬细胞和T细胞中，丁酸通过HDAC抑制促进抗炎表型的转化[23]。

（2）G蛋白偶联受体（GPCR）激活：丁酸是游离脂肪酸受体2（FFAR2，又称GPR43）、游离脂肪酸受体3（FFAR3，又称GPR41）及GPR109a的内源性配体[23]。FFAR2和FFAR3对SCFAs的链长选择性有所不同：FFAR2的激活效价为乙酸≈丙酸>丁酸，而FFAR3为丙酸≈丁酸>乙酸[24]。这些受体在肠道L细胞、免疫细胞及外周神经元中广泛表达，参与胰高血糖素样肽-1（GLP-1）、肽YY（PYY）分泌、调节性T细胞（Treg）分化及交感神经活性调节[25, 26]。

（3）能量底物作用：丁酸进入线粒体后经β-氧化生成乙酰辅酶A，进入三羧酸循环产生ATP。结肠细胞的大部分能量来源于丁酸氧化[27]。

图 1肠道基石菌酪酸梭菌基于丁酸介导的神经系统功能调控作用

3 酪酸梭菌/丁酸对肠-脑轴的调控机制

3.1 调节肠道屏障功能与系统性炎症

完整的肠道屏障是维持肠-脑轴稳态的前提。酪酸梭菌及其代谢产物丁酸可从多层面增强肠道屏障功能。酪酸梭菌灌胃可增加小鼠结肠黏蛋白MUC2的表达及黏膜厚度[28]。体外研究表明，丁酸可直接上调HT-29和Caco-2细胞中MUC基因的表达[29]。同时，酪酸梭菌处理可增加抗生素诱导菌群失调小鼠结肠组织中occludin、claudin-4及ZO-1等紧密连接蛋白的表达[28]。在创伤性脑损伤小鼠模型中，酪酸梭菌干预可降低血清D-乳酸水平，改善肠屏障功能[30]。

肠道屏障功能的增强可有效阻止脂多糖（LPS）等促炎因子从肠腔向系统性循环的易位[3, 31]。

3.2 调节免疫反应与神经炎症

酪酸梭菌在肠道黏膜免疫中发挥重要的调节功能，主要表现为促进Treg的分化和扩增。研究发现，酪酸梭菌可增加非肥胖糖尿病小鼠肠系膜淋巴结中Tregs的丰度，并降低胰腺中Th1、Th17促炎细胞的比例[32]。重要的是，丁酸本身也可通过HDAC抑制直接诱导Foxp3⁺ Treg细胞分化[33]。

小胶质细胞作为脑内常驻免疫细胞，其活化状态受肠道菌群的深刻影响。无菌小鼠小胶质细胞呈现未成熟表型，补充SCFAs混合物可恢复小胶质细胞的正常形态和功能[34]。在阿尔茨海默病小鼠模型中，酪酸梭菌灌胃可抑制小胶质细胞活化，降低白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）水平[35]。机制研究表明，丁酸通过抑制核因子κB（NF-κB）p65磷酸化及ERK/JNK信号通路发挥抗神经炎症作用[35, 36]。

3.3 调控血脑屏障完整性

血脑屏障（BBB）是维持脑内微环境稳态的关键结构。无菌小鼠血脑屏障通透性增加，occludin和claudin-5表达下降，而灌胃丁酸或定植产丁酸菌可恢复血脑屏障功能[37]。在创伤性脑损伤小鼠中，丁酸干预上调了紧密连接蛋白occludin和ZO-1的表达，减轻了脑水肿和血脑屏障破坏[38]。

3.4 表观遗传调控与神经可塑性

丁酸作为HDAC抑制剂，可通过提高组蛋白乙酰化水平调控神经可塑性相关基因的表达。在亨廷顿病小鼠模型中，丁酸治疗可增加脑内组蛋白H3和H4乙酰化水平，改善运动功能并延长生存期[39]。在阿尔茨海默病小鼠模型中，丁酸可增加海马H3K14、H4K5及H4K12位点的乙酰化，改善记忆功能[40]。丁酸还可上调星形胶质细胞中脑源性神经营养因子（BDNF）和胶质细胞源性神经营养因子（GDNF）的表达，通过HDAC抑制机制保护多巴胺能神经元[41]。

4 酪酸梭菌/丁酸在神经系统疾病中的应用研究

4.1 酪酸梭菌/丁酸在AD中的应用研究

AD是最常见的神经退行性疾病。临床研究发现，AD患者粪便中产丁酸菌丰度显著降低，丁酸水平下降[42, 43]。APP/PS1转基因AD小鼠经酪酸梭菌连续灌胃4周后，认知功能显著改善，脑内β-淀粉样蛋白42（Aβ42）水平降低，小胶质细胞活化被抑制，IL-1β和TNF-α水平下降[35]。此外，酪酸梭菌可改善侧脑室注射链脲佐菌素诱导的AD小鼠认知障碍，抑制海马和结肠组织中TLR4/MyD88/NF-κB信号通路，并恢复肠道菌群结构[44]。

4.2 酪酸梭菌/丁酸在PD中的应用研究

PD患者粪便中产丁酸菌丰度显著降低，粪便和血清丁酸水平下降[45]。给6-羟基多巴胺诱导的PD大鼠腹腔注射丁酸14天，发现丁酸可改善运动功能障碍，降低氧化应激，抑制神经炎症，增加纹状体BDNF水平[41]。丁酸灌胃可改善MPTP诱导的PD小鼠运动功能，增加结肠GLP-1表达及脑内GLP-1受体水平，同时上调occludin和ZO-1保护血脑屏障[46]。

4.3 酪酸梭菌/丁酸在抑郁症中的应用研究

抑郁症患者粪便中SCFAs水平降低[47]。给C57BL/6小鼠预防性灌胃酪酸梭菌4周后进行慢性社交挫败应激10天，发现酪酸梭菌预处理可减轻抑郁样行为，抑制海马小胶质细胞活化，降低结肠和海马中促炎性细胞因子IL-1β、IL-6、TNF-α水平[48]。丁酸还可减轻慢性不可预知温和应激小鼠的抑郁样行为，该效应与脑内BDNF水平升高有关[49]。

4.4 酪酸梭菌/丁酸在ASD中的应用研究

ASD患者常伴有胃肠道症状和肠道菌群紊乱。BTBR小鼠和丙戊酸诱导的ASD小鼠模型中，肠道通透性增加，紧密连接蛋白表达下降。灌胃酪酸梭菌3周可增加小鼠粪便丁酸水平，改善肠道屏障功能，减轻ASD样行为[50]。低剂量丁酸即可改善BTBR自闭症小鼠的社交行为缺陷，降低前额叶皮质兴奋性/抑制性基因表达比例[51]。

5 现状与局限性

尽管酪酸梭菌基于其代谢产物丁酸在神经系统疾病领域展现出令人鼓舞的应用前景，但当前研究仍存在一定局限性。例如，高质量的人体随机对照试验仍然不足。一项纳入9项研究的荟萃分析虽显示益生菌可降低CRP和MDA水平，但各研究间异质性较大，且均未单独验证酪酸梭菌的效应[52]。其次，丁酸的剂量-效应关系尚不明确，不同研究报道的有效剂量存在差异，其最佳治疗窗口有待进一步确定[41, 53]。此外，粪便丁酸浓度能否真实反映体内丁酸的中枢暴露水平，目前仍存争议[54]。尽管如此，这些不足恰恰为该领域的深入研究指明了方向，酪酸梭菌/丁酸在神经系统疾病防治中仍展现出巨大潜力。

6 总结与展望

肠道健康的基石菌酪酸梭菌，作为一种安全、有效的产丁酸益生菌，通过其代谢产物丁酸在肠-脑轴中发挥多靶点调节作用。丁酸通过HDAC抑制、GPCR激活及能量代谢三重机制，协同调节肠道屏障、系统性免疫及中枢神经炎症，在AD、PD、抑郁症、ASD等多种神经系统疾病中展现出治疗潜力。这一思路契合了通过调控肠道微生态干预中枢神经系统疾病的整合医学观点，为拓展神经系统疾病的防治策略提供了新的理论依据与研究思路。

我国在酪酸梭菌的基础研究与产业化应用方面已取得重要进展。其中，酪酸梭菌菌株CGMCC0313-1具有自主知识产权，相关技术已获得中国、美国双发明专利授权（CN01129258.X，US 8092793等）。基于该菌株开发的酪酸梭菌活菌制剂展现出良好的安全性与应用前景：酪酸梭菌活菌胶囊与酪酸梭菌活菌散等微生态制剂已实现规模化生产，并经国家药品监督管理局批准为绿标OTC药品[55-56]。上述成果为进一步探索酪酸梭菌基于丁酸调控肠-脑轴的神经系统疾病干预策略提供了可靠的菌株资源与制剂保障。

参考文献

[1] Scheltens P, De Strooper B, Kivipelto M, et al. Alzheimer's disease [J]. The Lancet, 2021, 397(10284): 1577-90.

[2] Agahi A, Hamidi G A, Daneshvar R, et al. Does severity of Alzheimer's disease contribute to its responsiveness to modifying gut microbiota? A double blind clinical trial [J]. Frontiers in neurology, 2018, 9: 662.

[3] Ren Y, Liang J, Xie J, et al. Sodium oligomannate modulates the gut-brain axis to alleviate post-stroke cognitive impairment by restoring butyrate metabolism [J]. Microbiome, 2026, 14(1): 6.

[4] Fink H A, Linskens E J, MacDonald R, et al. Benefits and harms of prescription drugs and supplements for treatment of clinical Alzheimer-type dementia: A systematic review and meta-analysis [J]. Annals of internal medicine, 2020, 172(10): 656-68.

[5] Hillman E T, Lu H, Yao T, et al. Microbial ecology along the gastrointestinal tract [J]. Microbes environments, 2017, 32(4): 300-13.

[6] Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing [J]. nature, 2010, 464(7285): 59-65.

[7] Cryan J F, O'Riordan K J, Cowan C S, et al. The microbiota-gut-brain axis [J]. Physiological reviews, 2019, 99(4): 1877-2013.

[8] Morais L H, Schreiber IV H L, Mazmanian S K. The gut microbiota–brain axis in behaviour and brain disorders [J]. Nature Reviews Microbiology, 2021, 19(4): 241-55.

[9] Den Besten G, Van Eunen K, Groen A K, et al. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism [J]. Journal of lipid research, 2013, 54(9): 2325-40.

[10] Koh A, De Vadder F, Kovatcheva-Datchary P, et al. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites [J]. Cell, 2016, 165(6): 1332-45.

[11] Stilling R M, Van De Wouw M, Clarke G, et al. The neuropharmacology of butyrate: the bread and butter of the microbiota-gut-brain axis? [J]. Neurochemistry international, 2016, 99: 110-32.

[12] Dalile B, Van Oudenhove L, Vervliet B, et al. The role of short-chain fatty acids in microbiota–gut–brain communication [J]. Nature reviews Gastroenterology hepatology, 2019, 16(8): 461-78.

[13] Seki H, Shiohara M, Matsumura T, et al. Prevention of antibiotic‐associated diarrhea in children by Clostridium butyricum MIYAIRI [J]. Pediatrics International, 2003, 45(1): 86-90.

[14] Stoeva M K, Garcia-So J, Justice N, et al. Butyrate-producing human gut symbiont, Clostridium butyricum, and its role in health and disease [J]. Gut microbes, 2021, 13(1): 1907272.

[15] Guo P, Zhang K, Ma X, et al. Clostridium species as probiotics: potentials and challenges [J]. Journal of animal science biotechnology, 2020, 11(1): 24.

[16] Louis P, Flint H J. Formation of propionate and butyrate by the human colonic microbiota [J]. Environmental microbiology, 2017, 19(1): 29-41.

[17] Bloemen J G, Venema K, Van De Poll M C, et al. Short chain fatty acids exchange across the gut and liver in humans measured at surgery [J]. Clinical nutrition, 2009, 28(6): 657-61.

[18] Donohoe D R, Garge N, Zhang X, et al. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon [J]. Cell metabolism, 2011, 13(5): 517-26.

[19] Vijay N, Morris M E. Role of monocarboxylate transporters in drug delivery to the brain [J]. Current pharmaceutical design, 2014, 20(10): 1487-98.

[20] Gerhart D Z, Enerson B E, Zhdankina O Y, et al. Expression of monocarboxylate transporter MCT1 by brain endothelium and glia in adult and suckling rats [J]. American Journal of Physiology-Endocrinology Metabolism, 1997, 273(1): E207-E13.

[21] Oldendorf W H. Carrier-mediated blood-brain barrier transport of short-chain monocarboxylic organic acids [J]. American Journal of Physiology-Legacy Content, 1973, 224(6): 1450-3.

[22] Fellows R, Denizot J, Stellato C, et al. Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases [J]. Nature communications, 2018, 9(1): 105.

[23] Chang P V, Hao L, Offermanns S, et al. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition [J]. Proceedings of the National Academy of Sciences, 2014, 111(6): 2247-52.

[24] Brown A J, Goldsworthy S M, Barnes A A, et al. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids [J]. Journal of Biological Chemistry, 2003, 278(13): 11312-9.

[25] Smith P M, Howitt M R, Panikov N, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis [J]. Science, 2013, 341(6145): 569-73.

[26] Nøhr M K, Egerod K L, Christiansen S H, et al. Expression of the short chain fatty acid receptor GPR41/FFAR3 in autonomic and somatic sensory ganglia [J]. Neuroscience, 2015, 290: 126-37.

[27] Roediger W. Utilization of nutrients by isolated epithelial cells of the rat colon [J]. Gastroenterology, 1982, 83(2): 424-9.

[28] Hagihara M, Kuroki Y, Ariyoshi T, et al. Clostridium butyricum modulates the microbiome to protect intestinal barrier function in mice with antibiotic-induced dysbiosis [J]. Iscience, 2020, 23(1).

[29] Burger-van Paassen N, Vincent A, Puiman P J, et al. The regulation of intestinal mucin MUC2 expression by short-chain fatty acids: implications for epithelial protection [J]. Biochemical Journal, 2009, 420(2): 211-9.

[30] Li H, Sun J, Du J, et al. Clostridium butyricum exerts a neuroprotective effect in a mouse model of traumatic brain injury via the gut‐brain axis [J]. Neurogastroenterology Motility, 2018, 30(5): e13260.

[31] Wang H, Zhang M, Li J, et al. Gut microbiota is causally associated with poststroke cognitive impairment through lipopolysaccharide and butyrate [J]. Journal of neuroinflammation, 2022, 19(1): 76.

[32] Jia L, Shan K, Pan L-L, et al. Clostridium butyricum CGMCC0313. 1 protects against autoimmune diabetes by modulating intestinal immune homeostasis and inducing pancreatic regulatory T cells [J]. Frontiers in immunology, 2017, 8: 1345.

[33] Furusawa Y, Obata Y, Fukuda S, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells [J]. Nature, 2013, 504(7480): 446-50.

[34] Erny D, Hrabě de Angelis A L, Jaitin D, et al. Host microbiota constantly control maturation and function of microglia in the CNS [J]. Nature neuroscience, 2015, 18(7): 965-77.

[35] Sun J, Xu J, Yang B, et al. Effect of Clostridium butyricum against microglia‐mediated neuroinflammation in Alzheimer's disease via regulating gut microbiota and metabolites butyrate [J]. Molecular nutrition food research, 2020, 64(2): 1900636.

[36] Liu J, Li H, Gong T, et al. Anti-neuroinflammatory effect of short-chain fatty acid acetate against Alzheimer’s disease via upregulating GPR41 and inhibiting ERK/JNK/NF-κB [J]. Journal of Agricultural Food Chemistry, 2020, 68(27): 7152-61.

[37] Braniste V, Al-Asmakh M, Kowal C, et al. The gut microbiota influences blood-brain barrier permeability in mice [J]. Science translational medicine, 2014, 6(263): 263ra158-263ra158.

[38] Li H, Sun J, Wang F, et al. Sodium butyrate exerts neuroprotective effects by restoring the blood-brain barrier in traumatic brain injury mice [J]. Brain research, 2016, 1642: 70-8.

[39] Ferrante R J, Kubilus J K, Lee J, et al. Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington's disease mice [J]. Journal of Neuroscience, 2003, 23(28): 9418-27.

[40] Govindarajan N, Agis-Balboa R C, Walter J, et al. Sodium butyrate improves memory function in an Alzheimer's disease mouse model when administered at an advanced stage of disease progression [J]. Journal of Alzheimer’s Disease, 2011, 26(1): 187-97.

[41] Sharma S, Taliyan R, Singh S. Beneficial effects of sodium butyrate in 6-OHDA induced neurotoxicity and behavioral abnormalities: modulation of histone deacetylase activity [J]. Behavioural brain research, 2015, 291: 306-14.

[42] Zhang L, Wang Y, Xiayu X, et al. Altered gut microbiota in a mouse model of Alzheimer’s disease [J]. Journal of Alzheimer’s Disease, 2017, 60(4): 1241-57.

[43] Ling Z, Zhu M, Yan X, et al. Structural and functional dysbiosis of fecal microbiota in Chinese patients with Alzheimer's disease [J]. Frontiers in Cell Developmental Biology, 2021, 8: 634069.

[44] Su Y, Wang D, Liu N, et al. Clostridium butyricum improves cognitive dysfunction in ICV-STZ-induced Alzheimer’s disease mice via suppressing TLR4 signaling pathway through the gut-brain axis [J]. PLoS One, 2023, 18(6): e0286086.

[45] Unger M M, Spiegel J, Dillmann K-U, et al. Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls [J]. Parkinsonism related disorders, 2016, 32: 66-72.

[46] Liu J, Wang F, Liu S, et al. Sodium butyrate exerts protective effect against Parkinson's disease in mice via stimulation of glucagon like peptide-1 [J]. Journal of the neurological sciences, 2017, 381: 176-81.

[47] Skonieczna-Żydecka K, Grochans E, Maciejewska D, et al. Faecal short chain fatty acids profile is changed in Polish depressive women [J]. Nutrients, 2018, 10(12): 1939.

[48] Tian T, Xu B, Qin Y, et al. Clostridium butyricum miyairi 588 has preventive effects on chronic social defeat stress-induced depressive-like behaviour and modulates microglial activation in mice [J]. Biochemical biophysical research communications, 2019, 516(2): 430-6.

[49] Sun J, Wang F, Hu X, et al. Clostridium butyricum attenuates chronic unpredictable mild stress-induced depressive-like behavior in mice via the gut-brain axis [J]. Journal of agricultural food chemistry, 2018, 66(31): 8415-21.

[50] Liu S, Xi H, Xue X, et al. Clostridium butyricum regulates intestinal barrier function via trek1 to improve behavioral abnormalities in mice with autism spectrum disorder [J]. Cell bioscience, 2024, 14(1): 95.

[51] Kratsman N, Getselter D, Elliott E. Sodium butyrate attenuates social behavior deficits and modifies the transcription of inhibitory/excitatory genes in the frontal cortex of an autism model [J]. Neuropharmacology, 2016, 102: 136-45.

[52] Tamtaji O R, Milajerdi A, Reiner Ž, et al. A systematic review and meta-analysis: the effects of probiotic supplementation on metabolic profile in patients with neurological disorders [J]. Complementary Therapies in Medicine, 2020, 53: 102507.

[53] Qiao C-M, Sun M-F, Jia X-B, et al. Sodium butyrate exacerbates Parkinson’s disease by aggravating neuroinflammation and colonic inflammation in MPTP-induced mice model [J]. Neurochemical research, 2020, 45(9): 2128-42.

[54] Primec M, Mičetić-Turk D, Langerholc T. Analysis of short-chain fatty acids in human feces: A scoping review [J]. Analytical Biochemistry, 2017, 526: 9-21.

[55] https://www.nmpa.gov.cn/datasearch/search- info.html?nmpa=aWQ9MjJmNGYzNWJmMGVmYzBjMTIzMmIxNjU0MmQwOGU0ZmYmaXRlbUlkPWZmODA4MDgxODNjYWQ3NTAwMTg0MDg4MWY4NDgxNzlm.

[56] https://www.nmpa.gov.cn/datasearch/search- info.html?nmpa=aWQ9ZTMyNzRjNWZiYTliMzQ5OWFjNDZmMTUzYTBmMThhNTcmaXRlbUlkPWZmODA4MDgxODNjYWQ3NTAwMTg0MDg4MWY4NDgxNzlm