title: Salivary microbiota reflects changes in gut microbiota in cirrhosis with hepatic encephalopathy.
abstract: Altered gut microbiome is associated with systemic inflammation and cirrhosis decompensation. However, the correlation of the oral microbiome with inflammation in cirrhosis is unclear. Our aim was to evaluate the oral microbiome in cirrhosis and compare with stool microbiome. Outpatients with cirrhosis (with/without hepatic encephalopathy [HE]) and controls underwent stool/saliva microbiome analysis (for composition and function) and also systemic inflammatory evaluation. Ninety-day liver-related hospitalizations were recorded. Salivary inflammation was studied using T helper 1 cytokines/secretory immunoglobulin A (IgA), histatins and lysozyme in a subsequent group. A total of 102 patients with cirrhosis (43 previous HE) and 32 age-matched controls were included. On principal component analysis (PCA), stool and saliva microbiome clustered far apart, showing differences between sites as a whole. In salivary microbiome, with previous HE, relative abundance of autochthonous families decreased whereas potentially pathogenic ones (Enterobacteriaceae, Enterococcaceae) increased in saliva. Endotoxin-related predicted functions were significantly higher in cirrhotic saliva. In stool microbiome, relative autochthonous taxa abundance reduced in previous 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. Thirty-eight 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 patients with cirrhosis); significantly higher interleukin (IL)-6/IL-1β, secretory IgA, and lower lysozyme, and histatins 1 and 5 were found in patients with cirrhosis, compared to controls.
  
  
  CONCLUSIONS
  Dysbiosis, represented by reduction in autochthonous bacteria, is present in both saliva and stool in patients with cirrhosis, compared to controls. Patients with cirrhosis have impaired salivary defenses and worse inflammation. Salivary dysbiosis was greater in patients with cirrhosis who developed 90-day hospitalizations. These findings could represent a global mucosal-immune interface change in cirrhosis.
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA.
authors.forename: Jasmohan S
authors.initials: JS
authors.lastname: Bajaj
authors.affiliation: Microbiome Analysis Center, George Mason University, Manassas, VA.
authors.forename: Naga S
authors.initials: NS
authors.lastname: Betrapally
authors.affiliation: Department of Microbiology, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA.
authors.forename: Phillip B
authors.initials: PB
authors.lastname: Hylemon
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA.
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Heuman
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA.
authors.forename: Kalyani
authors.initials: K
authors.lastname: Daita
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA.
authors.forename: Melanie B
authors.initials: MB
authors.lastname: White
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA.
authors.forename: Ariel
authors.initials: A
authors.lastname: Unser
authors.affiliation: Department of Biostatistics, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA.
authors.forename: Leroy R
authors.initials: LR
authors.lastname: Thacker
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA.
authors.forename: Arun J
authors.initials: AJ
authors.lastname: Sanyal
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, VA.
authors.forename: Dae Joong
authors.initials: DJ
authors.lastname: Kang
authors.affiliation: Microbiome Analysis Center, George Mason University, Manassas, VA.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Sikaroodi
authors.affiliation: Microbiome Analysis Center, George Mason University, Manassas, VA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Gillevet
mesh_terms: D064806:Dysbiosis; D005243:Feces / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome; D006501:Hepatic Encephalopathy / Q000150:complications / Q000382:microbiology*; D006801:Humans; D007249:Inflammation / Q000382:microbiology; D007422:Intestines / Q000382:microbiology*; D008103:Liver Cirrhosis / Q000150:complications / Q000382:microbiology*; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D012463:Saliva / Q000382:microbiology*
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