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Background and Aim: Several studies observed alterations in the gut microbiota in patients with non‐alcoholic fatty liver disease (NAFLD). However, analyzed patient populations and methods strongly differ among these studies. The aim of this study was to prove the reproducibility of published results and to provide a detailed overview of all findings in our NAFLD cohort using next generation sequencing methods.
Methods: The individual taxonomic microbiota composition of fecal samples from 90 NAFLD patients and 21 healthy controls was analyzed using 16S rRNA gene sequencing. Study participants were grouped according to their disease stage and compared regarding their gut microbiota composition. Studies were identified from PubMed listed publications, and the results were compared with the findings in our cohort.
Results: Results from 13 identified studies were compared with our data. A decreased abundance of the Bacteroidetes and Ruminococcaceae as well as an increased abundance of Lactobacillaceae and Veillonellaceae and Dorea were the most frequently reported changes among NAFLD patients in 4/13, 5/13, 4/13, 2/13, and 3/13 studies, respectively. Even though these alterations in the gut microbiota composition were also observed in our patient cohort, the majority of published differences could not be reproduced, neither in our own nor in other NAFLD cohort studies.
Conclusion: Despite repeatedly reproduced abundance patterns of specific bacteria, the heterogeneous study results did not reveal a consistent disease specific gut microbiota signature. Further prospective studies with homogenous patient cohorts and standardized methods are necessary to phenotype NAFLD by the gut microbiota.
Overconsumption of carbohydrates and lipids are well known to cause nonalcoholic fatty liver disease (NAFLD), while the role of nutritional protein intake is less clear. In Western diet, meat and other animal products are the main protein source, with varying concentrations of specific amino acids. Whether the amount or composition of protein intake is associated with a higher risk for disease severity has not yet been examined. In this study, we investigated associations of dietary components with histological disease activity by analyzing detailed 14‐day food records in a cohort of 61 patients with biopsy‐proven NAFLD. Furthermore, we used 16S ribosomal RNA gene sequencing to detect associations with different abundances of the gut microbiota with dietary patterns. Patients with definite nonalcoholic steatohepatitis (NAFLD activity score of 5‐8 on liver biopsy) had a significantly higher daily relative intake of protein compared with patients with a NAFLD activity score of 0‐4 (18.0% vs. 15.8% of daily protein‐based calories, P = 0.018). After adjustment for several potentially confounding factors, a higher protein intake (≥17.3% of daily protein‐based calories) remained associated with definite nonalcoholic steatohepatitis, with an odds ratio of 5.09 (95% confidence interval 1.22‐21.25, P = 0.026). This association was driven primarily by serine, glycine, arginine, proline, phenylalanine, and methionine. A higher protein intake correlated with a lower Bacteroides abundance and an altered abundance of several other bacterial taxa. Conclusion: A high protein intake was independently associated with more active and severe histological disease activity in patients with NAFLD. Further studies are needed to investigate the potential harmful role of dietary amino acids on NAFLD, with special attention to meat as their major source.
Serum levels of bone sialoprotein correlate with portal pressure in patients with liver cirrhosis
(2020)
Liver cirrhosis represents the common end-stage of chronic liver diseases regardless of its etiology. Patients with compensated disease are mostly asymptomatic, however, progression to a decompensated disease stage is common. The available stratification strategies are often unsuitable to identify patients with a higher risk for disease progression and a limited prognosis. SIBLINGs, soluble glycophosphoproteins, are secreted into the blood by immune-cells. While osteopontin, the most prominent member of the SIBLINGs family, has been repeatedly associated with liver cirrhosis, data on the diagnostic and/or prognostic value of bone sialoprotein (BSP) are scarce and partly inconclusive. In this study, we analyzed the diagnostic and prognostic potential of circulating BSP in comparison to other standard laboratory markers in a large cohort of patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt (TIPS). Serum levels of BSP were similar in patients with different disease stages and were not indicative for prognosis. Interestingly, BSP serum levels did correlate inversely with portal pressure, as well as its surrogates such as platelet count, the portal vein cross-sectional area and correlated positively with the portal venous velocity. In summary, our data highlight that BSP might represent a previously unrecognized marker for portal hypertension in patients with liver cirrhosis.
