Beneficial effects of LRP6-CRISPR on prevention of alcohol-related liver injury surpassed fecal microbiota transplant in a rat model

Abstract

Alcohol intake can modify gut microbiota composition, increase gut permeability, and promote liver fibrogenesis. LRP6 is a signal transmembrane protein and a co-receptor for the canonical Wnt signaling pathway. This study compared the curative effect of LRP6-CRISPR on alcohol-related liver injury with that of traditional fecal microbiota transplant (FMT) and investigated the alteration of the gut microbiome following the treatment. A rat model of alcohol-related liver injury was established and injected with lentiviral vectors expressing LRP6-CRISPR or administered with fecal filtrate from healthy rats, with healthy rat served as the control. Liver tissues of rats were examined by HE staining, Sirius staining, and Oil red O staining, respectively. The expression of LRP6 and fibrosis biomarkers were tested by PCR. The fecal sample of rats was collected and examined by 16S rRNA sequencing. Our data indicated that LRP6-CRISPR was more efficient in the prevention of alcohol-related liver injury than FMT. Microbiome analysis showed that alcoholrelated liver injury related to gut microbiota dysbiosis, while treatment with LRP6-CRISPR or FMT increased gut microflora diversity and improved gut symbiosis. Further, bacteria specific to the disease stages were identified. Genera Romboutsia, Escherichia-Shigella, Pseudomonas, Turicibacter, and Helicobacter were prevalent in the intestine of rats with alcohol-related liver injury, while the domination of Lactobacillus was found in rats treated with LRP6-CRISPR or FMT. Besides, Lactobacillus and genera belonging to family Lachnospiraceae, Bacteroidales S24-7 group, and Ruminococcaceae were enriched in healthy rats. LRP6-CRISPR and FMT have beneficial effects on the prevention of alcohol-related liver injury, and correspondently, both treatments altered the disrupted gut microflora to a healthy one.

Recovery Dynamics of Intestinal Bacterial Communities of CCl4-Treated Mice with or without Mesenchymal Stem Cell Transplantation over Different Time Points

“…Multiple S24-7 phylotypes were associated with all the MCS and CCl 4 groups, suggesting different S24-7 phylotypes could play different roles in each of the six groups. This is consistent with the previous findings, which hold different views on the roles of Bacteroidales S24-7 in the gut microbiota [ 35 , 36 ]. Multiple OTUs assigned to Clostridiales were associated with M48, among which OTU375_ Clostridiales was most associated with M48.…”

Dendropanax morbifera Leaf Extracts Improved Alcohol Liver Injury in Association with Changes in the Gut Microbiota of Rats

“…In this study, we observed that alcohol consumption increased Prevotella and Parasutterella and decreased Clostridium , Turcibacter and Romboutsia , which is in line with the previous reports [ 46 , 47 , 48 , 49 ]. Moreover, alcohol consumption also increased the abundance of some of the gram-negative bacteria (i.e, Porphyromonadaceae and Alloprevotella ).…”

Yeast Culture Improves Egg Quality and Reproductive Performance of Aged Breeder Layers by Regulating Gut Microbes

“…Romboutsia can metabolize carbohydrates, synthesize amino acids and vitamins, and are sensitive to bile acids ( Gerritsen et al, 2017 ). Some studies suggest that Romboutsia may be linked to obesity ( Hu et al, 2019 ) and liver injury ( Yu et al, 2020 ). Furthermore, a large number of studies have directly or indirectly proved that Romboutsia and Lactobacilli show opposing trends in relative abundance ( Chen et al, 2019 ; Lee et al, 2019 ; Qiao et al, 2019 ; Xu S. et al, 2020 ).…”