2024-04-25 16:50:00
The liver and intestines are connected directly through the portal vein, a blood vessel that carries nutrients absorbed in the intestines directly to the liver. The intestines are home to numerous intestinal bacteria, and sometimes these bacteria and their related substances can enter the liver through the portal vein.
Researchers at Osaka University have discovered how liver sentinel macrophages act in defense against intestinal bacteria and related substances that enter through the portal vein, particularly in conditions of compromised intestinal barrier. This finding is promising for the development of preventive and therapeutic strategies for chronic inflammatory liver diseases, such as steatohepatitis associated with metabolic dysfunction (MASH),
This is especially problematic when the intestinal barrier is compromised, as seen in conditions such as ulcerative colitis or leaky gut syndrome, allowing many intestinal bacteria and related substances to reach the liver. Under normal circumstances, the liver’s immune system is able to defend itself against invading intestinal bacteria and related substances and prevent inflammation, but the exact mechanism behind this was unclear.
Using innovative technologies such as in vivo liver imaging and single-cell gene expression analysis while preserving tissue location information, a research group from Osaka University School of Medicine has revealed that certain macrophages resident near the entrance of the liver protects it against intestinal bacteria and related substances. Additionally, the study found that isoalolithocholic acid (isoalo-LCA), a secondary bile acid produced by some intestinal bacteria, triggers the activation of these sentinel macrophages.
With the rise of conditions such as leaky gut due to modern lifestyles (stress, high-fat diets and lack of exercise), there is growing concern about inflammation affecting various organs, including the liver. Metabolic dysfunction-associated steatohepatitis (MASH), often accompanied by leaky gut, has been of particular concern due to its increasing incidence and challenging treatment.
This research sheds light on how liver sentinel macrophages defend against intestinal commensal invaders, offering hope that improving their functions could lead to the development of new preventive and therapeutic strategies for chronic inflammatory liver diseases, including MASH.
The study was published in the journal Nature.
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