Y Lapidot1,2,3, A Amir4, S Ben-Simon5, E Veitsman6,7, O Cohen-Ezra6, Y Davidov6, P Weiss6, T Bradichevski6, S Segev8, O Koren5, Z Ben-Ari9,6,10, M Safran9,6. 1. Liver Research Laboratory, Sheba Medical Center, Tel Hashomer, Israel. Lena.lapidot@gmail.com. 2. Liver Diseases Center, Sheba Medical Center, Tel Hashomer, Israel. Lena.lapidot@gmail.com. 3. The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Lena.lapidot@gmail.com. 4. Cancer Research Center, Sheba Medical Center, Ramat-Gan, Israel. 5. Faculty of Medicine, Bar-Ilan University, Safed, Israel. 6. Liver Diseases Center, Sheba Medical Center, Tel Hashomer, Israel. 7. The Liver Unit, Rambam Health Care Campus, Haifa, Israel. 8. Medical Screening Unit, Sheba Medical Center, Tel Hashomer, Israel. 9. Liver Research Laboratory, Sheba Medical Center, Tel Hashomer, Israel. 10. The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Abstract
BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic, progressive liver disease known for its frequent concurrence with inflammatory bowel disease. PSC can progress to cirrhosis, end-stage liver disease, hepatobiliary cancer, and/or colorectal cancer. The etiopathogenesis of PSC remains poorly understood, and, as such, pharmacotherapy has yet to be definitively established. Little is known about the salivary microbiome in PSC and PSC-IBD. This study aimed to evaluate the oral microbiome of patients with PSC, with association to these patient's fecal microbial composition. METHODS: Saliva, fecal samples and Food Frequency Questionnaires were collected from 35 PSC patients with or without concomitant inflammatory bowel disease and 30 age- and BMI-matched healthy volunteers. 16S rRNA gene sequencing was performed using Illumina MiSeq platform. RESULTS: The salivary microbial signature of PSC was significantly altered as compared to healthy controls, independent of concomitant IBD, and was comprised of 19 significantly altered species, of which, eight species were consistently overrepresented in both fecal and saliva of patients with PSC, including Veillonella, Scardovia and Streptococcus. CONCLUSIONS: PSC is characterized by microbial dysbiosis in the gut and the salivary microbiome, independently from IBD. The PSC dysbiotic signature includes a reduction in autochthonous bacteria and an increased relative abundance of pathogenic bacteria, including an invasion of oral bacteria to the gut. PSC is a strong modulator of the microbial profile, in the gut and the oral microbiome. These results may lead to the development of biomarkers for screening and early diagnosis or the development of personalized medicine in PSC.
BACKGROUND:Primary sclerosing cholangitis (PSC) is a chronic, progressive liver disease known for its frequent concurrence with inflammatory bowel disease. PSC can progress to cirrhosis, end-stage liver disease, hepatobiliary cancer, and/or colorectal cancer. The etiopathogenesis of PSC remains poorly understood, and, as such, pharmacotherapy has yet to be definitively established. Little is known about the salivary microbiome in PSC and PSC-IBD. This study aimed to evaluate the oral microbiome of patients with PSC, with association to these patient's fecal microbial composition. METHODS: Saliva, fecal samples and Food Frequency Questionnaires were collected from 35 PSC patients with or without concomitant inflammatory bowel disease and 30 age- and BMI-matched healthy volunteers. 16S rRNA gene sequencing was performed using Illumina MiSeq platform. RESULTS: The salivary microbial signature of PSC was significantly altered as compared to healthy controls, independent of concomitant IBD, and was comprised of 19 significantly altered species, of which, eight species were consistently overrepresented in both fecal and saliva of patients with PSC, including Veillonella, Scardovia and Streptococcus. CONCLUSIONS: PSC is characterized by microbial dysbiosis in the gut and the salivary microbiome, independently from IBD. The PSC dysbiotic signature includes a reduction in autochthonous bacteria and an increased relative abundance of pathogenic bacteria, including an invasion of oral bacteria to the gut. PSC is a strong modulator of the microbial profile, in the gut and the oral microbiome. These results may lead to the development of biomarkers for screening and early diagnosis or the development of personalized medicine in PSC.
Entities:
Keywords:
Cholestatic livers disease; Diet; Dysbiosis; Food frequency questionnaire; Gut; Gut liver axis; Liver; Microbiome; Primary sclerosing cholangitis; Saliva