The link is said to be cyclical, in that liver fibrosis results in gut flora imbalance, which in turn further aggravates liver fibrosis.
In a study led by researchers from Qingdao University, the role of gut flora in alcohol-induced liver fibrosis was investigated in a murine model.
The researchers randomly divided 36 six-week-old male mice into three groups of 12, each with different diets: one group was given alcohol, another alcohol and lincomycin hydrochloride (to induce gut flora imbalance), and the last was given alcohol, lincomycin hydrochloride and extra probiotics (to correct gut flora imbalance).
They then assessed different indicators of liver damage, including serum alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels.
Broken barriers
Serum ALP, AST and ALT levels were the highest in the mice that had consumed alcohol and lincomycin hydrochloride, and the lowest in the mice that had been given probiotics.
This was consistent with previous studies, which had reported that the serum ALP, AST and ALT levels were positively associated with liver injury.
At the same time, the mice given alcohol and lincomycin hydrochloride exhibited more severe liver fibrosis than the mice given only alcohol.
The researchers wrote that in the event of the intestinal barrier being damaged, "harmful substances such as bacteria and bacterial metabolites in the intestine can invade the liver through the enterohepatic cycle".
"This leads to over‑activation of the immune system and adverse immune reactions, which subsequently cause vast inflammatory cell infiltration, hepatocyte degeneration and necrosis."
Earlier research had shown that gut flora imbalance can lead to a rise in bacterial endotoxin level and the "secretion of inflammatory factors such as TNF‑α, interleukin (IL)‑1β and IL‑6".
This in turn worsens oxidative stress in the liver and results in lipid peroxidation and liver fibrosis.
Cyclical correction
The researchers stated that the results suggest that gut flora is important in maintaining liver homeostasis, and its imbalance leads to the cycle of liver fibrosis causing gut flora imbalance that further exacerbates it.
They concluded that "correcting intestinal flora imbalance is necessary to break this cycle and maintain liver homeostasis", and that "correcting intestinal flora imbalance is crucial and can be an effective method in the treatment of liver fibrosis".
Source: Oncology Letters
https://doi.org/10.3892/ol.2017.6762
"Intestinal flora imbalance promotes alcohol‑induced liver fibrosis by the TGFβ / smad signaling pathway in mice"
Authors: Dong Zhang, et al.