Lactulose is a synthetic disaccharide composed of galactose and fructose linked by a β-1,4-glycosidic bond, distinct from its precursor lactose. It is a non-absorbable sugar resistant to digestion in the small intestine due to the absence of appropriate human enzymes. As a result, lactulose reaches the colon unchanged, where it undergoes fermentation by gut microbiota.

The mechanism of action of lactulose relies primarily on its fermentation in the colon by saccharolytic bacteria, which metabolize lactulose into short-chain fatty acids (SCFAs), mainly lactic acid and acetic acid, along with gases such as hydrogen and methane. The production of SCFAs lowers the colonic pH, promoting the conversion of ammonia (NH₃) into ammonium ions (NH₄⁺), which are less readily absorbed. This “ammonia trapping” mechanism is clinically critical in reducing systemic ammonia levels, particularly in patients with hepatic encephalopathy.

Furthermore, lactulose fermentation increases osmotic pressure in the intestinal lumen, drawing water into the colon. This softens stool, stimulates peristalsis, and supports its effectiveness as an osmotic laxative. SCFAs also provide energy to colonic epithelial cells and promote the growth of beneficial bacteria such as lactobacilli and bifidobacteria, while inhibiting urease-producing harmful bacteria. These microbial shifts help reduce ammonia production and support overall intestinal health.

Clinical Applications of Lactulose

• Chronic Constipation: Lactulose softens stool and accelerates intestinal transit through its osmotic and fermentative actions.
• Hepatic Encephalopathy: By acidifying the colon and trapping ammonia, lactulose reduces systemic ammonia levels and improves neurological symptoms.
• Microbiota Modulation: Promotes beneficial bacteria and suppresses ammonia-producing species, improving gut health.

In summary, lactulose is a synthetic disaccharide whose therapeutic effects derive from colonic bacterial fermentation, SCFA production, acidification of the lumen, osmotic laxation, microbiota modulation, and ammonia trapping. These combined actions make lactulose an important agent in managing constipation and hepatic diseases.