How does alcohol gives the liver? The key mechanism of inflammation has been discovered (and how to avoid it)

How does alcohol gives the liver? The key mechanism of inflammation has been discovered (and how to avoid it)

By Dr. Kyle Muller

It is no mystery that chronic alcohol consumption can seriously damage the liver by inflaming it. Now a study published on Nature discovered the reason:

Alcohol seems to be able to deactivate an immune “alarm system” present in the intestine, allowing bad bacteria to leave their natural habitat by passing the liver and causing inflammation.

This would be the key mechanism behind the typical damage of alcoholic hepatopathy – called ALD, from English Alcohol-Associated Liver Disease.

Reversible process. Every year in Italy over 17,000 people die due to diseases related to alcohol consumption: the ALD is one of the most serious consequences of drinking, but there are still no therapies that they take care of abstinence.

This research turns on hope in this direction: in addition to identifying the mechanism that causes inflammation, in fact, experts have also discovered (for now only on mice) a way to overturn the process, closing the way to the escape of bacteria and restoring the order.

Out of control. The culprit of the inflammation would be a key receptor of the intestine called M4 (Machr4) receptor, which in those who consume alcohol regularly would be present in considerably reduced quantities.

The Machr4 is a sort of “supervisory system” which, in normal circumstances, orders the Caliciform cells to form small “checkpoints” called antigenic passages associated with the Caliciform cells (Gaps, from English Goblet-Cell-Agliadocated Antigen Passages).

These gaps allow small fragments of bacteria to switch to immune cells for a quick control that allows you to verify the absence of intestinal microbes. However, when Machr4’s activity is reduced, the bacteria are not blocked and pass in abundance to the liver.

Possible future therapies. The good news is that in a subsequent study conducted on mice, scientists managed to block this mechanism and invert it:

By stimulating a signaling path called Interleuchina 6 (IL-6), it was possible to reactivate the functions of Machr4 and restore the formation of gaps, blocking the uncontrolled flow of intestinal bacteria towards the liver.

What has been discovered, although it needs to be confirmed by more in -depth and large human studies, has great therapeutic potential for a disease that, so far, had no cure.

Kyle Muller
About the author
Dr. Kyle Muller
Dr. Kyle Mueller is a Research Analyst at the Harris County Juvenile Probation Department in Houston, Texas. He earned his Ph.D. in Criminal Justice from Texas State University in 2019, where his dissertation was supervised by Dr. Scott Bowman. Dr. Mueller's research focuses on juvenile justice policies and evidence-based interventions aimed at reducing recidivism among youth offenders. His work has been instrumental in shaping data-driven strategies within the juvenile justice system, emphasizing rehabilitation and community engagement.
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