A team of researchers has found that liver resident macrophages play a crucial role in protecting against gut bacteria and other substances that enter the body through the portal vein, especially when the intestinal barrier is compromised. These macrophages, known as ‘sentinel macrophages,’ are activated by a substance called isoallo-lithocholic acid. This discovery suggests that it may be possible to develop treatments for chronic liver inflammatory diseases, like metabolic dysfunction-associated steatohepatitis (MASH), by enhancing the function of these macrophages to reduce inflammation and improve the effectiveness of treatment.
Osaka University researchResearchers have found that liver resident macrophages play a crucial role in defending the body against gut bacteria and related substances that enter through the portal vein, especially when the intestinal barrier is compromised. These macrophages, known as “sentinel macrophages,” are activated by isoallo-lithocholic acid. This discovery has the potential to lead to the development of preventive and therapeutic strategies for chronic inflammatory liver diseases, such as metabolic dysfunction-associated steatohepatitis (MASH), by boosting the function of these macrophages to reduce inflammation and improve treatment effectiveness.
The liver and intestines are directly cThe portal vein connects the intestines to the liver, allowing nutrients to be transported directly from the intestines to the liver. The intestines contain a large number of gut bacteria, which can sometimes enter the liver through the portal vein along with their related substances. This can cause problems when the intestinal barrier is weakened, as is the case in conditions like ulcerative colitis or leaky gut syndrome, allowing a large number of gut bacteria and related substances to reach the liver. Normally, the liver’s immune system is able to defend against these invading gut bacteria and related substances and prevent inflammation, but the exact mechanism is not fully understood.The mechanism behind this was not clearly understood. Using advanced technologies such as in vivo imaging of the liver and analyzing the gene expression of individual cells while maintaining tissue location information, a team of researchers led by Yu Miyamoto and Masaru Ishii at the Graduate School of Medicine of Osaka University has discovered that specific resident macrophages near the liver entrance defend it against intestinal bacteria and related substances. Their discoveries are depicted in Figure 1. Dr. Miyamoto, who is one of the main authors of the study, stated, “Our technology demonstrated that these ‘sentinel macrophages’ play a critical role in protecting the liver.”The liver can become inflamed due to the presence of intestinal bacteria and related substances. The study also discovered that isoallo-lithocholic acid (isoallo-LCA), a type of bile acid produced by certain gut bacteria, is responsible for activating these sentinel macrophages. The increased prevalence of conditions like leaky gut, caused by modern lifestyles such as stress, high-fat diets, and lack of exercise, has raised concerns about inflammation affecting various organs, including the liver. Metabolic dysfunction-associated steatohepatitis (MASH), often linked to leaky gut, has become particularly concerning due to its growing incidence and challenges associated with it.The study focused on how liver sentinel macrophages protect against gut commensal invaders and how enhancing their functions could lead to new preventive and therapeutic strategies for liver chronic inflammatory diseases, such as MASH.
