Changes in the liver microbiome as a risk factor for the development of NAFLD in obese individuals
In this paper, Suppli et al., study the microbiome in liver biopsies and blood from healthy lean and obese patients:
→ Liver microbiome profiling separated obese and lean individuals.
→ Bacterial biomass (16S rRNA gene qPCR) was higher in liver from obese individuals.
→ The liver microbiome of obese individuals displayed a Proteobacteria-enriched signature.
→ The copy number of 16S rRNA gene strongly correlated with the Fatty Liver Index (FLI).
→ Changes in the liver microbiome could constitute a risk factor for the development of NAFLD.
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Hepatic microbiome in healthy lean and obese humans
Suppli MP, Bagger JI, Lelouvier B, Broha A, Demant M, Kønig MJ, Strandberg C, Lund A, Vilsbøll T, Knop FK. Hepatic microbiome in healthy lean and obese humans. JHEP Rep. 2021 Apr 27;3(4):100299. doi: 10.1016/j.jhepr.2021.100299. PMID : 34169247 ; PMCID : PMC8207208.
Dysbiosis 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.
We 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.
Histology 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).
We 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.
Non-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.
Keywords: FLI, fatty liver index; HbA1c, glycated haemoglobin; LEfSe, linear discriminant analysis effect size; Metabolic syndrome; Microbiome; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; Non-alcoholic fatty liver disease; OTU, operational taxonomic unit; Obesity; qPCR, quantitative polymerase chain reaction; rDNA, ribosomal DNA.
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