Is it time to spit? More evidence for the oral–gut–liver axis in liver disease

Abstract

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.