Is it time to spit? More evidence for the oral-gut-liver axis in liver disease.
Is it time to spit? More evidence for the oral-gut-liver axis in liver disease.
复制标题
是时候吐口水了吗？
DOI：
10.1007/s12072-021-10136-3
复制
发表时间：
2021
影响因子：
6.6
通讯作者：
Bajaj,JasmohanS
中科院分区：
文献类型：
--
作者：
Acharya,Chathur;Bajaj,JasmohanS
肠道-肝轴的变化，包括微生物组，与我们对肝病发病机制和进展的理解相关[1]。根据最近的论文，口腔和口腔-肠道-肝轴的概念在肝病患者中得到了越来越多的支持[2，3]。伴有和不伴有炎症性肠病(IBD)的原发性硬化性胆管炎(PSC)是肠肝轴改变的典型表现[4，5]。这些患者通常具有侵袭性疾病表型，中位死亡时间从10年到14.5年不等[6]。因此，明确PSC患者生物液中的微生物组对于设计新的治疗策略和改善预后，以提高这些患者的无移植生存率是重要的。PSC患者粪便和肠道粘膜微生物组的潜在失调模式已经发表得很好[4，5]。研究表明，与没有IBD的PSC相比，有IBD的PSC具有不同的微生物特征。与肝硬变相似，在PSC中，即使在疾病的早期，口腔致病菌，如链球菌和韦龙氏菌，在这些患者的粪便和粘膜中也显著丰富。然而，在PSC中，唾液微生物组还没有被发现。在Lapidot等人的研究中，PSC患者的粪便和唾液微生物组显示出微生物组成的变化，与IBD疾病活动无关[8]。这是PSC患者首次出现唾液微生物改变。这一结果扩展了先前的肝硬变研究，确实发现与非肝硬化组相比，有肝硬化组的PSC的唾液和粪便微生物变化更大。此外，结果显示，无论是粪便还是唾液，PSC患者的唾液葡萄球菌、微小弧菌、放线菌和双歧杆菌都比对照组更丰富。研究还发现，随机森林分类器可以使用唾液微生物区分健康对照组和PSC患者。然而，这些令人兴奋的结果需要一些语境来解释。这项研究是在一个人口中进行的，这个人口中有几个种族的丰富融合，具有不同的饮食和文化习俗，需要在其他环境中推广[9]。一些做法很可能会影响肠道和唾液微生物区系，甚至在肝病的后期，如肝硬变[10]。与以前的研究相比，梭状芽孢杆菌集群XIVa和B.ProductA的增加反映了这一点，并将使这些结果难以在其他群体中推广。此外，在这个相对温和的队列中，包括吸烟在内的几种饮食和生活方式做法在不同群体之间存在差异，风险混淆。另一个可能影响肠道微生物区系“口头化”的主要因素是质子泵抑制剂的使用，这里没有对其进行评估，因此需要考虑[7]。最后，提供唾液样本的患者的牙齿健康需要考虑，以避免将副现象贴上疾病相关标签。最终，Lapidot等人发表了这些发现。唾液比大便更容易收集，这给我们带来了希望，它可能是一种可行的生物流体，可以靶向微生物区系，以增强预测和开发针对PSC的微生物靶向治疗。
Changes in the gut–liver axis, including the microbiome, are relevant in our understanding of the pathogenesis and progression of liver disease [1]. With recent papers, the influence of the oral cavity and the concept of the oral–gut–liver axis is gaining ground in patients with liver disease [2, 3]. Primary sclerosing cholangitis (PSC) with and without coexisting inflammatory bowel disease (IBD) represents the quintessential expression of an altered gut-liver axis [4, 5]. These patients can often have an aggressive disease phenotype with a median time to death in ranging from 10 to 14.5 years [6]. Therefore, defining the microbiome in bio-fluids in patients with PSC is important to devise newer treatment strategies and for improving prognostication with the goal of improving transplant-free survival in these patients. The potential dysbiosis patterns of the fecal and gut mucosal microbiome in PSC patients are well published [4, 5]. Studies have shown that PSC with IBD has a different microbial signature compared to PSC without IBD. Similar to cirrhosis, oral pathobionts such as Streptococcus and Veillonella are significantly enriched in the stool and mucosa of these patients even in early stages of the disease in PSC [7]. However, the salivary microbiome is yet unexplored in PSC. In the study by Lapidot et al., the fecal and salivary microbiome of PSC patients demonstrated changes in microbial composition regardless of IBD disease activity [8]. This is the first experience of salivary microbial alteration in PSC. The results extend prior cirrhosis studies and indeed found that the salivary and fecal microbial changes were greater in PSC with cirrhosis compared to those without cirrhosis. Moreover, the results showed that S. salivarius, V. parvula, Actinomyces and Bifidobacterium spp were more enriched in PSC patients compared to controls regardless of stool or saliva. The study also found that random forest classifiers can separate out healthy controls from patients with PSC using salivary microbiota.These exciting results, however, require some contextualization for interpretation. The study was carried out in a population which has a rich amalgamation of several ethnicities with differing dietary and cultural practices and needs to be extended in other settings [9]. It is likely that some practices can influence gut and salivary microbiota even in the later stages of liver disease such as cirrhosis [10]. The increases in Clostridium cluster XIVa and B. producta, which contrasted with prior studies, reflect this and would make these results difficult to generalize in other populations. In addition, several dietary and lifestyle practices including smoking were different between groups and risk confounding in this relatively modest cohort. Another major factor that can influence “oralization” of the gut microbiota is the use of proton pump inhibitors, which was not evaluated here and is important to consider [7]. Lastly, the dental health of patients providing salivary samples needs to be considered to avoid labeling epiphenomena as disease related. Ultimately, these findings published by Lapidot et al. give us hope that saliva, which is easier to collect than stool, may be a viable biofluid towards targeting microbiota to enhance prognostication and develop microbially targeted therapies for PSC.
登录
查看更多内容
DOI：
--
发表时间：
1990
期刊：
影响因子：
--
作者：
R. P. Soler;A. Khokhar;J. Lautersztain;Salam Al Baker;K. Francis;D. M. Kiger;G. Berestein
通讯作者：
G. Berestein
对小鼠进行脂质体封装药物的淋巴内给药：抑制淋巴结中肿瘤转移生长的可能性。
DOI：
--
发表时间：
1981
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
V. Kaledin;N. Matienko;V. Nikolin;Y. V. Gruntenko;V. Budker
通讯作者：
V. Budker
影响因子：
13.5
作者：
J. Weinstein;L. Leserman
通讯作者：
J. Weinstein;L. Leserman
影响因子：
7.3
作者：
KHOKHAR, AR;ALBAKER, S;PEREZSOLER, R
通讯作者：
PEREZSOLER, R
用包裹在多层囊泡中的顺式-双-新癸酸-反式-R,R-1,2-二氨基环己烷铂 (II) 治疗和预防 M5076 网状肉瘤的实验性肝转移。
影响因子：
11.2
作者：
Perez-Soler,R;Khokhar,AR;Lopez-Berestein,G
通讯作者：
Lopez-Berestein,G