Abstract
Background & AimsDysbiosis of the gut microbiota in response to an energy-rich Western diet and the potential leak of bacteria and/or bacterial products from the intestine to the liver is perceived as a potential risk factor for the development of non-alcoholic fatty liver disease (NAFLD). We investigated the microbiome in liver biopsies from healthy lean and obese individuals and compared it with their blood microbiome.MethodsWe examined liver biopsies from 15 healthy lean and 14 obese individuals (BMI of 18.5–25 and 30–40 kg/m2, respectively). Bacterial 16S ribosomal DNA (rDNA) was analysed by quantitative polymerase chain reaction (qPCR) and 16S metagenomic sequencing targeting the hypervariable V3–V4 region. Metagenomic analysis was performed using the linear discriminant analysis effect size (LEfSe) algorithm. Data are medians with IQRs in brackets.ResultsHistology revealed hepatic steatosis in 13 obese individuals and in 2 lean individuals. A robust signal from qPCR revealed significantly higher amounts of bacterial rDNA copies in liver samples from obese individuals compared with those from lean individuals (148 [118–167] vs. 77 [62–122] 16S copies/ng DNA, p <0.001). Liver biopsies from the obese group were characterised by lower alpha diversity at the phylum level (Shannon index 0.60 [0.55–0.76] vs. 0.73 [0.62–0.90], p = 0.025), and metagenomic profiling revealed a significantly higher proportion of Proteobacteria in this group (81.0% [73.0–82.4%] vs. 74.3% [68.4–78.4%], p = 0.014).ConclusionsWe provide evidence for the presence of bacterial rDNA in the healthy human liver. Based on differences in the hepatic microbiome between obese individuals and healthy lean individuals, we suggest that changes in the liver microbiome could constitute an additional risk factor for the development of NAFLD.Lay summaryNon-alcoholic fatty liver disease (NAFLD) has become the most common liver disease globally, and new evidence suggests that obesity is associated with a disturbed gut bacterial composition, which may influence the development of NAFLD. We examined the composition of bacterial DNA in liver biopsies from healthy lean and obese individuals and found a different composition of bacterial DNA in liver biopsies from the obese group. We propose that the increased bacterial DNA load in the livers of obese individuals could constitute an early risk factor for the progression of NAFLD.Clinical trial numberNCT02337660
Highlights
Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease with an estimated global prevalence of 25%.1 NAFLD constitutes a spectrum of conditions ranging from simple, benign, and reversible steatosis over non-fibrotic non-alcoholic steatohepatitis (NASH) to NASH with fibrosis that can progress to cirrhosis and end-stage liver disease
We report an overabundance of bacterial ribosomal DNA in the livers of obese individuals with hepatic steatosis compared with that of lean individuals, primarily driven by Proteobacteria
Benign steatosis was found in 2 lean participants (7% and 40% steatosis), whereas it was present in 13 of 14 obese individuals covering a spectrum from less than 5% to 40% steatosis
Summary
Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disease with an estimated global prevalence of 25%.1 NAFLD constitutes a spectrum of conditions ranging from simple, benign, and reversible steatosis over non-fibrotic non-alcoholic steatohepatitis (NASH) to NASH with fibrosis that can progress to cirrhosis and end-stage liver disease. A robust signal from qPCR revealed significantly higher amounts of bacterial rDNA copies in liver samples from obese individuals compared with those from lean individuals (148 [118–167] vs 77 [62–122] 16S copies/ng DNA, p
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