The Gut-Liver Axis | Increased Intestinal Permeability

The Gut-Liver Axis: Introduction

The gut-liver axis denotes the bidirectional relationship between the gastrointestinal tract and the liver, mediated largely through the hepatic portal vein; it may be further noted that the hepatic portal vein transports nutrient-rich blood from the gastrointestinal tract to the liver. Moreover, the gut-liver axis also involves bile flow as well as systemic circulation (1, 2). This axis serves a central role in both nutrient metabolism as well as the detoxification of harmful substances; and disruptions within this system, including without limitation intestinal dysbiosis and increased intestinal permeability, can yield implications extending beyond digestive health (1, 2).

The Hepatic Portal Vein

The hepatic portal vein transports blood containing absorbed nutrients, microbial metabolites, and xenobiotics from the gastrointestinal tract to the liver, and this portal inflow provides approximately 75% of the liver’s total blood supply, with the remaining 25% delivered by the hepatic artery (3). Moreover, the portal vein branches extensively—ramifying into smaller portal venules that deliver blood to what are termed "hepatic sinusoids." Within each hepatic lobule, blood from these sinusoids flows centripetally toward the central vein, which subsequently drains into the hepatic veins and then into the inferior vena cava (IVC), returning the blood to the systemic venous circulation (3).

Bile Flow

Within the liver, bile is secreted by hepatocytes and transported through a network of bile canaliculi and ducts, which merge to form the common hepatic duct. This duct joins with a duct connected to the gallbladder, the cystic duct, to form the common bile duct. Moreover bile may be stored and concentrated in the gallbladder until released into the small intestine to aid in digestion. It may be further noted that bile is composed primarily of bile salts, phospholipids, cholesterol, conjugated bilirubin, electrolytes, and water (4).

Within the small intestine, bile acids, among other things, can emulsify fats, aiding in supporting lipid digestion and absorption. Moreover, approximately 95% of bile acids may be reabsorbed in the ileum, the final segment of the small intestine, and returned to the liver via the portal circulation. This is often regarded as the enterohepatic cycle (4).

Intestinal Hyperpermeability

When the intestinal barrier is characterized by a state of "hyperpermeability," several biological phenomena may be observed and/or can be linked. Without limitation, these may include alterations in the microbial community or dysbiosis, movement of microorganisms or their components beyond the intestinal epithelial lining, and increased immune activity within the gut environment. Such changes may contribute to a cycle in which the barrier’s structure and function remain under ongoing stress. Moreover, compromise of the intestinal barrier may permit the passage of microbial constituents and metabolites into the portal circulation, potentially exposing the liver to these luminal-derived constituents. Such exposure can potentially negatively influence hepatic activity and homeostasis, underscoring the tightly integrated physiology of the gut–liver axis (1, 2).

Conclusion

In conclusion, the gut–liver axis represents a dynamic interface through which the gastrointestinal tract and liver maintain metabolic and immunological balance. Through the coordinated exchange of metabolites, bile constituents, and more, this system supports essential processes in digestion, detoxification, and nutrient assimilation.

Supporting Intestinal Health

General examples of natural compounds, ingredients, or minerals that may aid in supporting intestinal health:

1. Quercetin: A naturally occurring flavonol present in an array of plants including onions and apples. Quercetin may support intestinal health and barrier integrity (5, 6).

2. Deglycyrrhizinated Licorice (DGL): Deglycyrrhizinated licorice (DGL) is a form of licorice root extract from which much of the compound glycyrrhizin has been removed. DGL May aid in supporting digestion as well as intestinal health and mucus production (7).

3. Zinc: Zinc is an essential mineral; zinc may aid in supporting intestinal barrier function, tight junction integrity, and more (8, 9, 10).

4. Slippery Elm: Slippery elm contains mucilage polysaccharides and may aid in supporting gastrointestinal health (11).

5. Marshmallow Root: Marshmallow root contains mucilage polysaccharides and may aid in supporting gastrointestinal health (12).

6. Aloe Vera: Aloe vera contains polysaccharides, such as acemannan, and may aid in supporting intestinal barrier function  (17, 18, 13).

7. N-Acetylglucosamine (NAG): N-Acetylglucosamine (NAG) is an amino sugar that serves as a building block in the carbohydrate chains of mucins; supplemental NAG may support intestinal barrier integrity (14).

8. Glutamine: Glutamine is an amino acid that serves various functions, including acting as a fuel source for enterocytes (intestinal epithelial cells). Supplemental glutamine can support intestinal barrier integrity (15, 16).

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