Periodontal therapy favorably modulates the oral-gut-hepatic axis in cirrhosis

Abstract

Cirrhosis is associated with a systemic pro-inflammatory milieu, endotoxemia and gut dysbiosis. The oral cavity could be an additional source of inflammation. We aimed to determine the effect of periodontal therapy in cirrhosis through evaluating endotoxemia, inflammation, cognition and quality of life (QOL). Age-matched cirrhotic/non-cirrhotic subjects exhibiting chronic gingivitis and/or mild/moderate periodontitis underwent periodontal therapy with follow-up at 30 days. Saliva/stool for microbial composition and serum for MELD score, endotoxin and lipopolysaccharide binding protein (LBP) and immune-inflammatory markers (IL-1β, IL-6, histatins 1, 3, 5 and lysozyme) were collected at baseline and day 30. The cognitive function and QOL were also evaluated similarly. A separate group of cirrhotic patients were followed for the same duration without periodontal therapy. Cirrhotics, especially those with hepatic encephalopathy (HE), demonstrated improved dysbiosis in stool and saliva, and improved endotoxin, LBP and salivary/serum inflammatory mediators following periodontal therapy. These parameters, which were higher in HE at baseline, became statistically similar post-therapy. Pre vs post-therapy QOL and cognition also improved in HE patients following oral interventions. On the other hand, LBP and endotoxin increased over time in cirrhotics not receiving therapy, rest of the parameters, including microbiota remained similar over time in the no-therapy group. This proof-of-concept study demonstrates that periodontal therapy in cirrhosis, especially in those with HE, is associated with improved oral and gut dysbiosis, systemic inflammation, MELD score and cognitive function, which was not observed in those who did not receive therapy over the same time-period.

Oral Bacteria and Intestinal Dysbiosis in Colorectal Cancer

“…The importance of periodontitis and related bacteria in the modulation of gut dysbiosis became profound after periodontal therapy in patients with cirrhosis [78]. This led to improvement in intestinal dysbiosis, with increased commensal bacteria (Ruminococcaceae and Lachnospiraceae) and decreased opportunistic pathogens (Enterobacteriaceae) in addition to reduced taxa of oral origin (Porphyromonadaceae and Streptococcaceae) in fecal samples in cirrhotic patients, especially in those with hepatic encephalopathy.…”

Predicting Overt Hepatic Encephalopathy for the Population With Cirrhosis

“…Beyond measures of liver function, portal hypertension (as captured by thrombocytopenia, varices, and portal manometry) is independently associated with the risk of HE, reflecting increased systemic distribution of neurotoxic substances from the splanchnic circulation through portosystemic shunting. Because of the skeletal muscle's role in ammonia metabolism, sarcopenia is associated with hyperammonemia and can be observed clinically, measured directly using conventional imaging tools. The peripheral (shunted) burden of gut bacteria is proinflammatory and strongly linked to the development of cognitive dysfunction in patients with cirrhosis . The gastrointestinal microbiome is accessible at least in the context of research studies, and its specific constituents are associated with (or causally linked to) the risk of HE . Inflammatory cytokines are not routinely measured in clinical practice; however, should they become commercially available, they may discriminate the risk for HE …”

Management of Lifestyle Factors in Individuals with Cirrhosis: A Pragmatic Review

“…103 In a proofof-concept study, therapy of periodontitis led to improved intestinal dysbiosis and improved HE. 104 Hence, lifestyle adaptations in cirrhosis should include a careful oral health (teeth brushing at least twice per day; visit to the dentist at least once per year).…”