Salivary microbiota reflects changes in gut microbiota in cirrhosis with hepatic encephalopathy

Abstract

Background Altered gut microbiome is associated with systemic inflammation and cirrhosis decompensation. However, the correlation of the oral microbiome with inflammation in cirrhosis is unclear. Aim Evaluate the oral microbiome in cirrhosis and compare with stool microbiome. Methods Cirrhotic outpatients [with/without hepatic encephalopathy (HE)] and controls underwent stool/saliva microbiome analysis (for composition and function) and also systemic inflammatory evaluation. 90-day liver-related hospitalizations were recorded. Salivary inflammation was studied using Th1 cytokines/secretory IgA, histatins and lysozyme in a subsequent group. Results 102 cirrhotics (43 prior-HE) and 32 age-matched controls were included. On PCO, stool and saliva microbiome clustered far apart showing differences between sites as a whole. Salivary microbiome With prior-HE, relative abundance of autochthonous families decreased while potentially pathogenic ones (Enterobacteriaceae, Enterococcaceae) increased in saliva. Endotoxin-related predicted functions were significantly higher in cirrhotic saliva. Stool microbiome Relative autochthonous taxa abundance reduced in prior-HE, along with increased Enterobacteriaceae and Enterococcaceae. Cirrhotic stool microbiota demonstrated a significantly higher correlation with systemic inflammation compared to saliva microbiota on correlation networks. Outcomes 38 patients were hospitalized within 90 days. Their salivary dysbiosis was significantly worse and predicted this outcome independent of cirrhosis severity. Salivary inflammation was studied in an additional 86 age-matched subjects (43 controls/43 cirrhotics); significantly higher IL-6/IL-1β, secretory IgA and lower lysozyme, and histatins 1 and 5 were found in cirrhotics compared to controls. Conclusions Dysbiosis, represented by reduction in autochthonous bacteria, is present in both saliva and stool in cirrhosis patients compared to controls. Cirrhotic patients have impaired salivary defenses and worse inflammation. Salivary dysbiosis was greater in cirrhotics who developed 90-day hospitalizations. These findings could represent a global mucosal-immune interface change in cirrhosis.

Microbiota, cirrhosis, and the emerging oral-gut-liver axis

“…Additionally, there is evidence that the microbiome influences progression of NAFLD, ALD, and viral hepatitis to end-stage liver disease in humans (46,47), highlighting dysbiosis as a possible common denominator in these diseases. Dysbiosis has been documented in stool, sigmoid colonic mucosa, small intestinal mucosa, ascites, liver, serum, and saliva from cirrhotic patients (4,5,7,12,(48)(49)(50), pointing toward a global mucosal immune change in cirrhosis that permits widespread change in the microbiota. In one of the first studies to look at the gut microbiome using current culture-independent techniques, Chen et al demonstrated that fecal microbiota from cirrhosis patients exhibits a relative reduction in Bacteroidetes, an increase in Proteobacteria and Fusobacteria, but change in Firmicutes compared with microbiome from healthy individuals (5).…”

“…A study on the influence of the oral-gut-liver axis in cirrhosis directly compared the salivary microbiome in cirrhotic patients and healthy controls to the stool microbiome and analyzed salivary inflammation and prediction of 90-day hospitalizations (7). Similar to stool, autochthonous taxa (Lachnospiraceae, Ruminococcaceae, Clostridiales Incertae Sedis XIV) were reduced, while Enterobacteriaceae was increased in the saliva in cirrhotic patients compared with healthy controls.…”

“…Currently, viral hepatitis (hepatitis C and B) is the leading cause of cirrhosis worldwide; however, NAFLD/NASH is on track to become the most common etiology of chronic liver disease, especially in those with diabetes (2,3). There is a strong link between the gut microbiota and cirrhosis outcomes, a relationship that needs to be further explored (4)(5)(6)(7). Similar to the effect of gut microbiota on cirrhosis, emerging evidence also suggests that there is a possible link between a dysbiotic oral microenvironment and liver diseases.…”

The oral cavity microbiota: between health, oral disease, and cancers of the aerodigestive tract

“…Among these, we can list generalized diseases, such as rheumatoid arthritis (Zheng et al 2015), cardiovascular disease (Ordovas and Mooser 2006), and pulmonary diseases (Scannapieco and Genco 1999), as well as brain and liver abscesses (Wagner et al 2006). Other such illnesses include gastrointestinal cancer (Meurman and Grönroos 2010), breast cancer (Laidi et al 2016), cirrhosis (Bajaj et al 2015), and diabetes (Maruyama et al 2007;Deshpande et al 2010;Farag and Gaballa 2011). More recently, links with pregnancy (Digiulio et al 2015), the human immunodeficiency virus (HIV) (Kistler et al 2015), and acquired immune deficiency syndrome (AIDS) have also been described (Zheng et al 2015).…”

Oro‐hepatic link, endotoxemia, and systemic inflammation: The role of chronic periodontitis

“…Systemic endotoxemia, typically originating from the gut, is associated with liver damage, progression of liver disease, and cirrhosis decompensation. Bajaj et al (1) suggest an additional role of oral microbiota toward the overall endotoxemia and systemic inflammation in cirrhosis.…”