Salivary microbiota reflects changes in gut microbiota in cirrhosis with hepatic encephalopathy
Open accessAbstract
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. (H epatology 2015;62:1260‐1271)
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Recent studies show differences in duodenal and salivary microbiota between healthy controls and patients with cirrhosis, suggesting upper gastrointestinal changes may link to distal microbiota and contribute to chronic liver disease pathophysiology and hepatocellular carcinoma.
“Recent studies have demonstrated differences in the duodenal and salivary microbiota between healthy controls and patients with cirrhosis86,88, suggesting that there are also qualitative and quantitative changes in the upper gastrointestinal tract that might be linked to changes in the more distal microbiota and contribute to the pathophysiology of CLD as well as the development of HCC.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [88]
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- Authors
- Bajaj, J. S., Betrapally, N. S., Hylemon, P. B., Heuman, D. M., Daita, K., White, M. B., Unser, A., Thacker, L. R., Sanyal, A. J., Kang, D. J., Sikaroodi, M., & Gillevet, P. M.
- Affiliations
- Virginia Commonwealth University (US)
- George Mason University (US)
- Corresponding author
- Bajaj, Jasmohan S.
- ORCID
- Venue
- Hepatology
- Published
- 2015-05-06
- Volume
- 62
- Issue
- 4
- Pages
- 1260-1271
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC4587995
- OpenAlex
- W1518286619
- Cited by
- 325
- References
- 43
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 28 · 2023: 38 · 2022: 22 · 2021: 50 · 2020: 35 · 2019: 34 · 2018: 33 · 2017: 21 · 2016: 16 · 2015: 14
- FWCI
- 12.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 CX001076)
- National Institute on Alcohol Abuse and Alcoholism (R01AA020203, RO1AA020203)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK087913)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- liver cirrhosis, hepatic encephalopathy, salivary microbiota, gut microbiota, dysbiosis, systemic inflammation, Enterobacteriaceae, Enterococcaceae, endotoxin, secretory IgA, histatins, lysozyme, interleukin-6, IL-1β, mucosal immunity, hepatic decompensation
- MeSH terms
- Gastrointestinal Microbiome, Feces, Female, Hepatic Encephalopathy, Humans, Inflammation, Intestines, Liver Cirrhosis, Male, Middle Aged, Saliva, Microbiota, Dysbiosis
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