Circadian Rhythms Coordinated With Gut Microbiota Partially Account for Individual Differences in Hepatitis B-Related Cirrhosis

Abstract

Cirrhosis is the end stage of chronic liver diseases like chronic hepatitis B. In China, hepatitis B accounts for around 60% of cases of cirrhosis. So far, clinical and laboratory indexes for the early diagnosis of cirrhosis are far from satisfactory. Nevertheless, there haven’t been specific drugs for cirrhosis. Thus, it is quite necessary to uncover more specific factors which play their roles in cirrhosis and figure out the possible therapeutic targets. Among emerging factors taking part in the initiation and progression of cirrhosis, gut microbiota might be a pivot of systemic factors like metabolism and immune and different organs like gut and liver. Discovery of detailed molecular mechanism in gut microbiota and gut liver axis leads to a more promising prospect of developing new drugs intervening in these pathways. Time-based medication regimen has been proofed to be helpful in hormonotherapy, especially in the use of glucocorticoid. Thus, circadian rhythms, though haven’t been strongly linked to hepatitis B and its complications, are still pivotal to various pathophysiological progresses. Gut microbiota as a potential effective factor of circadian rhythms has also received increasing attentions. Here, our work, restricting cirrhosis to the post-hepatitis B one, is aimed to summarize how circadian rhythms and hepatitis B-related cirrhosis can intersect via gut microbiota, and to throw new insights on the development of new and time-based therapies for hepatitis B-related cirrhosis and other cirrhosis.

Oxidative stress bridges the gut microbiota and the occurrence of frailty syndrome

“…Regulating the GM and OS by diet or TCM could help to improve frailty. Additionally, there is increasing evidence indicating that circadian rhythms may also play important roles in mediating the impact of the GM on chronic diseases[ 74 ]. Clarifying the mechanisms involved in frailty from the perspective of the GM may be important to achieving the goal of healthy aging.…”

Brain-gut-liver axis: Chronic psychological stress promotes liver injury and fibrosis via gut in rats

“…Intestinal bacteria and endotoxin (mainly composed of LPS) are translocated to mesenteric lymph nodes or other extraintestinal parts, where they bind to LPS binding protein (LBP) with transport function, and then transport LPS to the cell membrane to bind to CDl4, thus forming the LPS-LBP-CDl4 complex. This complex then enters the liver through the circulation of the portal vein, triggering a cascade of intracellular signals in liver through TLR4, which eventually leads to exacerbated liver fibrosis ( Seki et al., 2007 ), cirrhosis ( Milosevic et al., 2019 ; Wang et al., 2022 ) and even liver cancer ( Meng et al., 2018 ). This interaction effect between the gut microbiota and the liver mediated by the LPS-TLR4 signaling pathway is called the gut-liver axis ( Seki et al., 2007 ; Chassaing et al., 2014 ; Cheng et al., 2022 ).…”

“…Progressive liver disease is often accompanied by gut microbial imbalance, intestinal endotoxemia and bacterial translocation ( Nolan, 2010 ; Macnaughtan and Jalan, 2015 ; Shim and Jeong, 2020 ; Yang X. et al., 2020 ; Park et al., 2022 ). Lipopolysaccharide (LPS), the main component of endotoxin, can activate intracellular signal transduction by the use of toll-like receptor 4 (TLR4) in the liver, thus exacerbating liver inflammation, and promoting the progression of liver fibrosis, which is the “gut-liver” axis ( Seki et al., 2007 ; Szabo, 2015 ; Tilg et al., 2020 ; Mandato et al., 2021 ; Rao et al., 2021 ; T Wang et al., 2022 ). Besides, an interactive effect between psychological stress and the gut has also been confirmed by the studies in rats, which is the “brain-gut” axis ( Stasi et al., 2012 ; Arotcarena et al., 2020 ; Hulme et al., 2020 ; Deng et al., 2021 ).…”

Crosstalk between circadian clocks and pathogen niche

“…Hepatic viruses can promote the formation of hepatocellular carcinoma, and the expression of Per1-3 and Cry2 was reduced in this tissue, which indicates that the crosstalk is bidirectional [ 49 – 51 ]. Interestingly, the initiation and progression of virus-related liver cirrhosis was partially regulated by the gut microbiota through the gut–liver axis [ 52 ], and microbiota regulated the circadian liver transcriptome and detoxification pattern [ 53 ].…”