Intrahepatic bacterial metataxonomic signature in non-alcoholic fatty liver disease

Abstract

<jats:sec><jats:title>Objective</jats:title><jats:p>We aimed to characterise the liver tissue bacterial metataxonomic signature in two independent cohorts of patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) diagnosis, as differences in the host phenotypic features—from moderate to severe obesity—may be associated with significant changes in the microbial DNA profile.</jats:p></jats:sec><jats:sec><jats:title>Design and methods</jats:title><jats:p>Liver tissue samples from 116 individuals, comprising of 47 NAFLD overweight or moderately obese patients, 50 NAFLD morbidly obese patients elected for bariatric surgery and 19 controls, were analysed using high-throughput 16S rRNA gene sequencing.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Liver bacterial DNA profile significantly differs between morbidly obese and non-morbidly obese patients with NAFLD. Bacteroidetes (p=1.8e-18) and Firmicutes (p=0.0044) were over-represented in morbidly obese patients and Proteobacteria (p=5.2e-10)—specifically Gammaproteobacteria and Alphaproteobacteria, and Deinococcus-Thermus (p=0.00012)—were over-represented in the non-morbidly obese cohort. Cohort-specific analysis of liver microbial DNA signatures shows patterns linked to obesity. The imbalance in Proteobacteria (Alpha or Gamma) among non-morbidly obese patients, and Peptostreptococcaceae, Verrucomicrobia, Actinobacteria and Gamma Proteobacteria DNA among morbidly obese patients was associated with histological severity. Decreased amounts of bacterial DNA from the Lachnospiraceae family were associated with more severe histological features. Proteobacteria DNA was consistently associated with lobular and portal inflammation scores. Microbial DNA composition corresponded to predicted functional differences.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>This is the first comprehensive study showing that the liver tissue of NAFLD patients contains a diverse repertoire of bacterial DNA (up to 2.5×10<jats:sup>4</jats:sup> read counts). The liver metataxonomic signature may explain differences in the NAFLD pathogenic mechanisms as well as physiological functions of the host.</jats:p></jats:sec>

Integrated Metagenomic and Metabolomic Analyses of the Effect of Astragalus Polysaccharides on Alleviating High-Fat Diet–Induced Metabolic Disorders

“…Our data showed HFD increased the abundance of Firmicutes and decreased abundance of Bacteroidetes, while APS was effective in reversing these changes. A large number of clinical studies show that fecal microbiota from patients with non-alcoholic fatty liver and cirrhotic contained an increased abundance of Firmicutes and a decreased abundance of Bacteroidetes (Wei et al, 2016;Sookoian et al, 2020). Increased Firmicutes can produce more lipopolysaccharide and deoxycholic acid, which pass into the liver through hepatic portal vein, leading to inflammation in the liver (Yoshimoto et al, 2013;Bourzac, 2014).…”

Microbiota changes and intestinal microbiota transplantation in liver diseases and cirrhosis

“…20 Thus, it is possible that endogenously produced alcohol from microbiota can cause fatty liver disease. These widespread microbial changes have been described in the circulating and hepatic microbiome in recent studies, 21,22 although changes in the circulating microbiome have been disputed vis-à-vis contaminants. 23 While the contribution of gut microbiota towards NAFLD development is being investigated, further studies disentangling NAFLD from the overlay of diseases such as diabetes are needed.…”

NAFLD and increased risk of cardiovascular disease: clinical associations, pathophysiological mechanisms and pharmacological implications

“…3-(4-hydroxyphenyl)-lactate, mainly derived from Proteobacteria, was associated (in two independent patient cohorts) with hepatic steatosis and degree of fibrosis [84]. Bacterial components may also be present in the livers in NAFLD, as a meta-taxonomic signature and also increased endotoxin has been detected in the livers [85,86]. All these studies support a role for intestinal microbiota in NAFLD pathogenesis and hold the promise that manipulation at this level might improve liver disease phenotype.…”