a School of Industrial Technology, Universiti Sains Malaysia , Penang , Malaysia .
Crit Rev Biotechnol. 2015;35(3):392-401. doi: 10.3109/07388551.2014.889077.
Probiotic microorganisms have been documented over the past two decades to play a role in cholesterol-lowering properties via various clinical trials. Several mechanisms have also been proposed and the ability of these microorganisms to deconjugate bile via production of bile salt hydrolase (BSH) has been widely associated with their cholesterol lowering potentials in prevention of hypercholesterolemia. Deconjugated bile salts are more hydrophobic than their conjugated counterparts, thus are less reabsorbed through the intestines resulting in higher excretion into the feces. Replacement of new bile salts from cholesterol as a precursor subsequently leads to decreased serum cholesterol levels. However, some controversies have risen attributed to the activities of deconjugated bile acids that repress the synthesis of bile acids from cholesterol. Deconjugated bile acids have higher binding affinity towards some orphan nuclear receptors namely the farsenoid X receptor (FXR), leading to a suppressed transcription of the enzyme cholesterol 7-alpha hydroxylase (7AH), which is responsible in bile acid synthesis from cholesterol. This notion was further corroborated by our current docking data, which indicated that deconjugated bile acids have higher propensities to bind with the FXR receptor as compared to conjugated bile acids. Bile acids-activated FXR also induces transcription of the IBABP gene, leading to enhanced recycling of bile acids from the intestine back to the liver, which subsequently reduces the need for new bile formation from cholesterol. Possible detrimental effects due to increased deconjugation of bile salts such as malabsorption of lipids, colon carcinogenesis, gallstones formation and altered gut microbial populations, which contribute to other varying gut diseases, were also included in this review. Our current findings and review substantiate the need to look beyond BSH deconjugation as a single factor/mechanism in strain selection for hypercholesterolemia, and/or as a sole mean to justify a cholesterol-lowering property of probiotic strains.
在过去的二十年中，已记录表明益生菌微生物通过各种临床试验在降低胆固醇特性方面发挥作用。也提出了几种机制，并且这些微生物通过产生胆汁盐水解酶（BSH）使胆汁脱共轭的能力与它们在预防高胆固醇血症中的降低胆固醇潜力广泛相关。与共轭胆汁盐相比，脱共轭胆汁盐更疏水，因此通过肠吸收的量较少，导致更多排泄到粪便中。作为前体的胆固醇替代新的胆汁盐，随后导致血清胆固醇水平降低。然而，由于脱共轭胆汁酸的活性抑制了胆固醇生成胆汁酸，因此出现了一些争议。脱共轭胆汁酸与一些孤儿核受体（如法尼醇 X 受体（FXR））具有更高的结合亲和力，导致胆固醇 7-α羟化酶（7AH）的酶合成受到抑制，该酶负责从胆固醇合成胆汁酸。这一观点进一步得到了我们当前对接数据的证实，该数据表明，与共轭胆汁酸相比，脱共轭胆汁酸具有更高的与 FXR 受体结合的倾向。胆汁酸激活的 FXR 还诱导 IBABP 基因的转录，导致胆汁酸从肠内回收到肝脏的循环增强，从而减少了新的胆固醇形成胆汁酸的需求。由于胆汁盐脱共轭增加可能导致的有害影响，例如脂类吸收不良、结肠癌发生、胆结石形成和肠道微生物群改变，这些因素导致了其他不同的肠道疾病，也包括在本综述中。我们目前的发现和综述证实，需要超越 BSH 脱共轭作为选择高胆固醇血症菌株的单一因素/机制，以及/或作为证明益生菌菌株降低胆固醇特性的唯一手段。
