丁酸梭菌

丁酸梭菌（Clostridium butyricum）又称丁酸菌、酪酸梭菌、酪酸菌、宫入菌，是一种梭状芽孢菌，在科学分类上归类于梭菌目梭菌科梭菌属的一种细菌。

丁酸梭菌
科学分类
域：	细菌域 Bacteria
门：	芽孢杆菌门 Bacillota
纲：	梭菌纲 Clostridia
目：	梭菌目 Clostridiales
科：	梭菌科 Clostridiaceae
属：	梭菌属 Clostridium
种：	丁酸梭菌 C. butyricum
二名法
Clostridium butyricum

丁酸梭菌常见于酸牛奶、乳酪中，能发酵肠道中的纤维及抗性淀粉产生大量丁酸，在日本、韩国和中国被广泛作为益生菌。^[1]

历史

第一个酪酸菌在1933年由日本千叶医科大学宫入近治博士首先从粪便分离出C.butyricum MIYAIRI菌株，因此，又名宫入菌(MIYAIRI 588株)，俗称CBM588^[2]，尔后，陆续有其他菌株被发现，如：RH2^[3]、S-45-5^[4]、UBCB 70^[5]、CGMCC0313^[6]...等。

功能

酪酸菌为人体肠道正常菌群之一，约有700多株，其中安全性高且具有治疗效果的菌株编号为第588株，称为宫入菌(CBM 588)，其能代谢肠道内的植物纤维而产生短链脂肪酸。能通过胃酸、肠液和胆汁，具有抑制多种致病菌生长和繁殖，促进结肠上皮细胞增殖，有利于损伤上皮的修复，平衡肠道菌丛生态等功能。酪酸菌在日本^[7]、韩国以及中国^[8]等亚洲国家和地区已被广泛用于防治肠道菌群失调所致的急慢性腹泻、抗生素相关性肠炎、便秘或腹泻便秘交替症、胃十二指肠溃疡合并幽门螺旋杆菌感染、过敏性肠易激综合症状(IBS)等疾病、免疫调节以及癌症辅助治疗，疗效良好^[9]。

特性

1. 耐酸性: 能在胃酸（pH1~2）中生存，而后在肠道增殖。
2. 耐热性: 55℃下仍然可全数存活菌数。
3. 对抗生素的耐受性: 对抗生素有较强的耐受性，与第一二线、甚至后线抗生素并用时不影响其活性，同时有效预防抗生素引发的腹泻及副作用。^{[10][11][12][13][14][15]}
4. 预防癌症: 抑制MDSC，诱导TLS(三级淋巴结构)^[16]、诱导PMN释放TRAIL^[17]，活化NK细胞^[18]进而提升抗癌能力，产生短链脂肪酸，可促进肠道上皮细胞修复，促进癌细胞之凋亡，故能防癌；并可加强化学治疗^[16]、放射线治疗之效果。
5. 增强抗癌效果：增强免疫检查点抑制剂及化疗治疗效果^[16][19][20]，降低化疗药物造成的肾脏损伤^[21]
6. 强化免疫攻击能力：促进自然杀手细胞与巨噬细胞活性、诱导 IgM 抗体形成与 γ 型 干扰素产生，增强胞杀及吞噬作用。^[18]
7. 平衡免疫系统：刺激调节性T细胞生成，调控身体免疫反应，减缓致敏 IgE 抗体，调节过敏体质。宫入菌（CBM588）的细胞壁之肽聚糖刺激肠道内膜中树状细胞，促进具有强大抗炎症作用的蛋白质TGF-β的分泌，进而TGF-β诱导抑制性Ｔ细胞．而抑制性Ｔ细胞具有抑制肠道内过度的炎症、过敏反应等作用，在人体免疫起着重要的作用．为此，服用CBM 588在预防和治疗炎症性肠疾病以及过敏症等是安全有效的方法。 ^[22][23]
8. 预防肠漏症及呼吸道感染：提升黏膜防御能力，促进γδT细胞生成，刺激肠壁保护因子制造，诱导IgA抗体分泌，产生短链脂肪酸，保护并修复黏膜屏障。^[24]
9. 抑制白色念珠菌及乙型链球菌：增强免疫系统之胞杀及吞噬作用，可预防女性泌尿生殖系统感染及降低孕妇乙型链球菌在阴道和直肠中的移生率。^[18][25]
10. 抑制肠内有害菌，调整肠道菌群: 酪酸菌能与双歧杆菌、乳酸菌等肠内有益菌共生，并促进其发育。
11. 抑制幽门杆菌: 可抑制幽门杆菌，加强三合一、四合一疗法效果，酪酸又可促进溃疡愈合可用于预防/治疗胃、十二指肠溃疡。^[10][11][12]
12. 抑制困难梭菌：与后线抗生素并用，加强治疗效果及降低副作用，预防伪膜性结肠炎之发生。^[11][13][14]
13. 增进血中Biotin(生物素)提升免疫功能：酪酸菌(宫入菌CBM 588)增进血中Biotin浓度之能力为益生菌中最高，一般达到乳酸菌增进Biotin血中之浓度2倍或以上。有害菌（坏菌）会分解Biotin造成血中Biotin浓度受限，此类病患皆与“免疫机能失调”有关。因血中Biotin之浓度与淋巴球CD4，CD8细胞为逆向关系，此为免疫失调之证明。坏菌之产物及其复合物结合成块，影响免疫系统，细菌（有害菌）之复合物在关节及皮肤组织沉淀，造成关节、皮肤等疾病。投与宫入菌+Biotin可有效治疗以下疾病 1. Sternocostoclavicular hyperostosis (SCCH)胸肋锁骨异常骨化症 2. Rheumotoid arthritis (类风湿性关节炎)3. Atopic dermatitis (异位性皮肤炎)。^[26]
14. 具调节神经传导、免疫作用、内分泌等作用，进而缓解忧郁症状，宫入菌(CBM 588)与抗忧郁剂并用治疗TRD(抑郁症)患者尤其是耐药性抑郁症患者具有安全性和有效性且可降低抗忧郁剂的副作用。宫入菌(CBM 588)辅助治疗耐药性抑郁症(TRD)之试验证实，以HAM-D-17，BDI和BAI评级量表评估，对于攻击或自残症状未发作前的忧郁症患者，70.0％的患者有效，35.0％的症状解除。^[27]
15. 改善牙周病引起的肠道疾病：牙周病患者反复发生腹泻症状常被误为肠躁症，实为口腔致病菌经由消化道及淋巴系统诱导Th17细胞迁移至肠道中所造成，宫入菌(CBM588)可抑制Th17形成，改善肠道发炎及类肠躁症之症状。^[28]
16. 改善脂肪代谢：肝脏中过氧化体(peroxisome)的减少与脂肪肝形成相关，而宫入菌(CBM 588)能够提升肝脏中过氧化体，加强脂肪酸分解代谢，改善血脂问题。^[29]

实验文献

• 酪酸菌调节肠道平衡,改善慢性肠道炎症(IBD )

Probiotics Clostridium butyricum and Bacillus subtilis ameliorate intestinal tumorigenesis. J Gastroenterol (2015) 50:928–939

• 酪酸菌代谢物丁酸盐可降低脂肪生成

Clostridium butyricum reduce lipogenesis through bacterial wall components and butyrate.Appl Microbiol Biotechnol (2014) 98:7549–7557

• 酪酸菌和枯草芽孢杆菌抑制直肠癌细胞增殖,促进肿瘤细胞凋亡

Probiotics Clostridium butyricum and Bacillus subtilis ameliorate intestinal tumorigenesis. Future Microbiology, Vol.10(9)(2015),1433‐1445

• 酪酸菌抑制膀胱癌

Clostridium butyricum MIYAIRI 588 shows antitumor effects by enhancing the release of TRAIL from neutrophils through MMP‐8 ,Int. J of oncology ,42: 903‐ 911, 2013

• 酪酸菌治疗肠内有害菌群引起之免疫失调疾病

Implication of Harmful Intestinal Microflora in the Pathogenesis of Disease with Immune Dysfunction Bioscience microflora vol.17 (1) 55~60, 1998

• 酪酸菌 Clostridium butyricum MIYAIRI 588(CBM 588) 抑制白色念珠菌增强免疫系统之胞杀及吞噬作用

Protection Activity Induced by the Bacterial Vaccine, Heat-Killed Clostridium butyricum Against Candida albicans Infections in Mice Volume 28, Issue 2 , 262-269, 1987

• 酪酸菌抑制肠炎和过敏症的可能性-肠内细菌诱导免疫调节蛋白和免疫调节细胞，具有肠道免疫保持恒常性的机转

Smad2 and Smad3 Inversely Regulate TGF-β Autoinduction in Clostridium butyricum-Activated Dendritic Cells Kashiwagi, Ikkou et al.Immunity , Volume 43 , Issue 1 , 65-79 ,2015

• 酪酸益生菌 宫入菌 Clostridium butyricum MIYAIRI 588(CBM 588)肾脏病可增加儿童原发性肾病症候群(INS)患者体内产酪酸的肠道菌和血液Treg数量，减少INS患者的复发频率及降低对免疫抑制剂（Rituximab）的需要。

Clinical Significance of Probiotics for Children with Idiopathic Nephrotic Syndrome Nutrients, 13(2), 365, 2021

• 酪酸益生菌 宫入菌 Clostridium butyricum MIYAIRI 588(CBM 588)作为治疗耐药性抑郁症的辅助治疗

Clostridium butyricum MIYAIRI 588 as Adjunctive Therapy for Treatment-Resistant Major Depressive Disorder:A Prospective Open-Label Trial Tsuyoshi Miyaoka, MD, PhD, Clinical Neuropharmacology, Volume 41, Number 5, September/October 2018, 151-115

• 酪酸菌 Clostridium butyricum MIYAIRI 588(CBM 588)与免疫检查点抑制剂(ICB)合并使用，提高非小细胞肺癌患者存活率 Association of Probiotic Clostridium butyricum Therapy with Survival and Response to Immune Checkpoint Blockade in Patients with Lung Cancer Cancer Immunol Res (2020) 8 (10): 1236–1242.

• 酪酸益生菌 宫入菌 Clostridium butyricum MIYAIRI 588(CBM 588)可增强术前化疗的胰腺癌患者抗癌免疫力

Intestinal Care Using L‒Glutamine Supplement and Probiotics Can Induce a Strong Anti‒Tumor Immune Response through the Induction of Mature Tertiary Lymphoid Structures in Pancreatic Cancer Patients Receiving Preoperative Chemotherapy 癌と化学疗法 Volume 48, Issue 4, 465 - 471 (2021)

• 酪酸菌 Clostridium butyricum MIYAIRI 588(CBM 588)透过调节肠道菌群以提升转移性肾细胞癌患者之免疫治疗临床治疗效果

Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial Nature Medicine , VOL 28, April 2022, 704–712

• 酪酸菌 Clostridium butyricum MIYAIRI 588(CBM 588) 改善牙周病引起的肠道疾病及类肠躁症之症状

The Intermucosal Connection between the Mouth and Gut in Commensal Pathobiont-Driven Colitis Cell, Volume 182, Issue 2, 23 July 2020, Pages 447-462.e14

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