丁酸梭菌

丁酸梭菌（Clostridium butyricum）又稱丁酸菌、酪酸梭菌、酪酸菌、宮入菌，是一種梭狀芽孢菌，在科學分類上歸類於梭菌目梭菌科梭菌屬的一種細菌。

丁酸梭菌
科學分類
域：	細菌域 Bacteria
門：	芽孢桿菌門 Bacillota
綱：	梭菌綱 Clostridia
目：	梭菌目 Clostridiales
科：	梭菌科 Clostridiaceae
屬：	梭菌屬 Clostridium
種：	丁酸梭菌 C. butyricum
二名法
Clostridium butyricum

丁酸梭菌常見於酸牛奶、乳酪中，能發酵腸道中的纖維及抗性澱粉產生大量丁酸，在日本、韓國和中國被廣泛作為益生菌。^[1]

歷史

第一個酪酸菌在1933年由日本千葉醫科大學宮入近治博士首先從糞便分離出C.butyricum MIYAIRI菌株，因此，又名宮入菌(MIYAIRI 588株)，俗稱CBM588^[2]，爾後，陸續有其他菌株被發現，如：RH2^[3]、S-45-5^[4]、UBCB 70^[5]、CGMCC0313^[6]...等。

功能

酪酸菌為人體腸道正常菌群之一，約有700多株，其中安全性高且具有治療效果的菌株編號為第588株，稱為宮入菌(CBM 588)，其能代謝腸道內的植物纖維而產生短鏈脂肪酸。能通過胃酸、腸液和膽汁，具有抑制多種致病菌生長和繁殖，促進結腸上皮細胞增殖，有利於損傷上皮的修復，平衡腸道菌叢生態等功能。酪酸菌在日本^[7]、韓國以及中國^[8]等亞洲國家和地區已被廣泛用於防治腸道菌群失調所致的急慢性腹瀉、抗生素相關性腸炎、便秘或腹瀉便秘交替症、胃十二指腸潰瘍合併幽門螺旋桿菌感染、過敏性腸易激綜合症狀(IBS)等疾病、免疫調節以及癌症輔助治療，療效良好^[9]。

特性

1. 耐酸性: 能在胃酸（pH1~2）中生存，而後在腸道增殖。
2. 耐熱性: 55℃下仍然可全數存活菌數。
3. 對抗生素的耐受性: 對抗生素有較強的耐受性，與第一二線、甚至後線抗生素併用時不影響其活性，同時有效預防抗生素引發的腹瀉及副作用。^{[10][11][12][13][14][15]}
4. 預防癌症: 抑制MDSC，誘導TLS(三級淋巴結構)^[16]、誘導PMN釋放TRAIL^[17]，活化NK細胞^[18]進而提升抗癌能力，產生短鏈脂肪酸，可促進腸道上皮細胞修復，促進癌細胞之凋亡，故能防癌；並可加強化學治療^[16]、放射線治療之效果。
5. 增強抗癌效果：增強免疫檢查點抑制劑及化療治療效果^[16][19][20]，降低化療藥物造成的腎臟損傷^[21]
6. 強化免疫攻擊能力：促進自然殺手細胞與巨噬細胞活性、誘導 IgM 抗體形成與 γ 型 干擾素產生，增強胞殺及吞噬作用。^[18]
7. 平衡免疫系統：刺激調節性T細胞生成，調控身體免疫反應，減緩致敏 IgE 抗體，調節過敏體質。宮入菌（CBM588）的細胞壁之肽聚糖刺激腸道內膜中樹狀細胞，促進具有強大抗炎症作用的蛋白質TGF-β的分泌，進而TGF-β誘導抑制性Ｔ細胞．而抑制性Ｔ細胞具有抑制腸道內過度的炎症、過敏反應等作用，在人體免疫起着重要的作用．爲此，服用CBM 588在預防和治療炎症性腸疾病以及過敏症等是安全有效的方法。 ^[22][23]
8. 預防腸漏症及呼吸道感染：提升黏膜防禦能力，促進γδT細胞生成，刺激腸壁保護因子製造，誘導IgA抗體分泌，產生短鏈脂肪酸，保護並修復黏膜屏障。^[24]
9. 抑制白色念珠菌及乙型鏈球菌：增強免疫系統之胞殺及吞噬作用，可預防女性泌尿生殖系統感染及降低孕婦乙型鏈球菌在陰道和直腸中的移生率。^[18][25]
10. 抑制腸內有害菌，調整腸道菌群: 酪酸菌能與雙歧桿菌、乳酸菌等腸內有益菌共生，並促進其發育。
11. 抑制幽門桿菌: 可抑制幽門桿菌，加強三合一、四合一療法效果，酪酸又可促進潰瘍癒合可用於預防/治療胃、十二指腸潰瘍。^[10][11][12]
12. 抑制困難梭菌：與後線抗生素併用，加強治療效果及降低副作用，預防偽膜性結腸炎之發生。^[11][13][14]
13. 增進血中Biotin(生物素)提升免疫功能：酪酸菌(宮入菌CBM 588)增進血中Biotin濃度之能力為益生菌中最高，一般達到乳酸菌增進Biotin血中之濃度2倍或以上。有害菌（壞菌）會分解Biotin造成血中Biotin濃度受限，此類病患皆與「免疫機能失調」有關。因血中Biotin之濃度與淋巴球CD4，CD8細胞為逆向關係，此為免疫失調之證明。壞菌之產物及其複合物結合成塊，影響免疫系統，細菌（有害菌）之複合物在關節及皮膚組織沉澱，造成關節、皮膚等疾病。投與宮入菌+Biotin可有效治療以下疾病 1. Sternocostoclavicular hyperostosis (SCCH)胸肋鎖骨異常骨化症 2. Rheumotoid arthritis (類風濕性關節炎)3. Atopic dermatitis (異位性皮膚炎)。^[26]
14. 具調節神經傳導、免疫作用、內分泌等作用，進而緩解憂鬱症狀，宮入菌(CBM 588)與抗憂鬱劑併用治療TRD(抑鬱症)患者尤其是耐藥性抑鬱症患者具有安全性和有效性且可降低抗憂鬱劑的副作用。宮入菌(CBM 588)輔助治療耐藥性抑鬱症(TRD)之試驗證實，以HAM-D-17，BDI和BAI評級量表評估，對於攻擊或自殘症狀未發作前的憂鬱症患者，70.0％的患者有效，35.0％的症狀解除。^[27]
15. 改善牙周病引起的腸道疾病：牙周病患者反覆發生腹瀉症狀常被誤為腸躁症，實為口腔致病菌經由消化道及淋巴系統誘導Th17細胞遷移至腸道中所造成，宮入菌(CBM588)可抑制Th17形成，改善腸道發炎及類腸躁症之症狀。^[28]
16. 改善脂肪代謝：肝臟中過氧化體(peroxisome)的減少與脂肪肝形成相關，而宮入菌(CBM 588)能夠提升肝臟中過氧化體，加強脂肪酸分解代謝，改善血脂問題。^[29]

實驗文獻

• 酪酸菌調節腸道平衡,改善慢性腸道炎症(IBD )

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

• 酪酸菌代謝物丁酸鹽可降低脂肪生成

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

• 酪酸菌和枯草芽孢桿菌抑制直腸癌細胞增殖,促進腫瘤細胞凋亡

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

• 酪酸菌治療腸內有害菌群引起之免疫失調疾病

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) 抑制白色念珠菌增強免疫系統之胞殺及吞噬作用

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

• 酪酸菌抑制腸炎和過敏癥的可能性-腸內細菌誘導免疫調節蛋白和免疫調節細胞，具有腸道免疫保持恆常性的機轉

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 宮入菌 Clostridium butyricum MIYAIRI 588(CBM 588)腎臟病可增加兒童原發性腎病症候群(INS)患者體內產酪酸的腸道菌和血液Treg數量，減少INS患者的復發頻率及降低對免疫抑製劑（Rituximab）的需要。

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

• 酪酸益生菌 宮入菌 Clostridium butyricum MIYAIRI 588(CBM 588)作為治療耐藥性抑鬱症的輔助治療

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)與免疫檢查點抑制劑(ICB)合併使用，提高非小細胞肺癌患者存活率 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 宮入菌 Clostridium butyricum MIYAIRI 588(CBM 588)可增強術前化療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 癌と化學療法 Volume 48, Issue 4, 465 - 471 (2021)

• 酪酸菌 Clostridium butyricum MIYAIRI 588(CBM 588)透過調節腸道菌群以提升轉移性腎細胞癌患者之免疫治療臨床治療效果

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) 改善牙周病引起的腸道疾病及類腸躁症之症狀

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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