The physiological functions of L-threonine and the digestive system

I. Construction and Repair of Intestinal Mucosal Barrier

As a core raw material for mucosal structural proteins, L-threonine plays an irreplaceable role in maintaining the intestinal physical barrier:

1. Key Substrate for Mucin Synthesis

Threonine accounts for 12%-15% of total amino acids in mucins (e.g., MUC2) synthesized by intestinal goblet cells, and its hydroxyl group forms a mucus gel layer through O-glycosylation. Threonine deficiency reduces the thickness of the intestinal mucus layer by 40% and mucin concentration in mucus by 30% in mice, causing direct contact between intestinal flora and epithelial cells and increasing inflammation risk. Clinical studies show that the expression of threonine transporter (e.g., B⁰AT1) in intestinal mucosa of inflammatory bowel disease (IBD) patients is down-regulated, and threonine supplementation can restore mucus layer thickness to 80% of the normal level.

2. Maintenance of Epithelial Tight Junctions

Threonine is involved in forming serine/threonine phosphorylation sites in tight junction proteins (e.g., ZO-1, occludin), regulating the assembly of junction proteins through the mTOR signaling pathway. Experiments show that threonine deficiency reduces the transepithelial electrical resistance (TEER) of Caco-2 cell monolayers by 50% and increases intestinal permeability, while supplementing 0.5 mM threonine can increase TEER values by 35%, approaching normal physiological conditions.

II. Regulatory Effects on Intestinal Immunity and Inflammation

L-threonine affects the immune homeostasis of the digestive system by regulating immune cell functions and inflammatory factor networks:

1. Metabolic Support for Immunoglobulin Secretion

When B cells in intestinal Peyer's patches differentiate into plasma cells, threonine, as a component of immunoglobulin (IgA) heavy and light chains (accounting for 6%-8% of amino acid residues), directly affects the secretion of intestinal mucosal IgA. Experiments in weaned piglets show that threonine deficiency reduces the concentration of IgA in intestinal fluid by 45%, while supplementing 0.3% threonine can restore and increase IgA levels by 20%, enhancing the intestinal neutralizing ability against pathogens.

2. Balance Regulation of Proinflammatory and Anti-Inflammatory Factors

Glycine produced by threonine decomposition can reduce the release of proinflammatory factors such as TNF-α and IL-6 by inhibiting the NF-κB pathway. In the TNBS-induced colitis model, the level of IL-6 in the colon tissue of mice in the threonine intervention group is reduced by 30%, and the secretion of anti-inflammatory factors such as IL-10 is promoted. The mechanism is related to glycine activating the GlyR receptor and inhibiting M1 polarization of macrophages.

III. Synergistic Regulation of Intestinal Flora and Metabolism

Metabolites of L-threonine can act as signaling molecules or nutritional substrates for intestinal flora, affecting the structure and function of the flora:

1. Substrate Supply for Flora Metabolism

Intestinal anaerobes (such as Bacteroides) can decompose threonine into propionic acid and butyric acid, of which butyric acid, as the main energy source for intestinal epithelial cells (providing 70% of energy needs), can promote epithelial cell proliferation. Studies have found that supplementing threonine increases the concentration of propionic acid in the cecum of mice by 25%, the concentration of butyric acid by 30%, and the abundance of Bacteroidetes by 15%, and the ratio of Firmicutes to Bacteroidetes decreases. This change in flora structure is positively correlated with the relief of intestinal inflammation.

2. Flora-Host Metabolic Interaction

Threonine affects the signal transduction of flora metabolites by regulating receptors such as farnesoid X receptor (FXR) and GPR43. For example, short-chain fatty acids (SCFAs) derived from threonine can activate GPR43, promote the secretion of GLP-1 by intestinal L cells, improve glucose metabolism, and enhance intestinal peristalsis and mucus secretion, forming a regulatory loop of "amino acid-flora-intestinal barrier".

IV. Regulation of Digestive Enzyme Secretion and Absorption Function

The functional regulation of L-threonine on the digestive system penetrates the whole process of digestion and absorption:

1. Promoting Effect on Pancreatic Digestive Enzyme Synthesis

As an essential raw material for pancreatic acinar cells to synthesize trypsin and chymotrypsin, insufficient threonine supply will reduce the content of digestive zymogens in rat pancreatic tissue by 25%, and the excretion of fat and protein in feces will increase by 15%-20%. Mechanistically, threonine promotes ribosome biosynthesis and zymogen granule assembly by activating the mTORC1 pathway. Supplementing threonine in experiments can increase the number of pancreatic zymogen granules by 30%.

2. Transport Regulation of Intestinal Nutrient Absorption

In jejunal epithelial cells, threonine enters cells through transporters (such as SLC6A19) coupled with Na⁺-K⁺-ATPase, and simultaneously promotes the cotransport of glucose, amino acids, etc. When the threonine concentration is 1 mM, the absorption rate of glucose in Caco-2 cells increases by 22%, and this synergistic effect is related to the phosphorylation modification of transporter proteins. In addition, threonine deficiency will reduce the density of intestinal mucosal microvilli by 20% and the activity of brush border enzymes (such as alkaline phosphatase) by 18%, affecting the absorption efficiency of nutrients.

V. Protective Effects on the Digestive System in Pathological States

Supplementation with L-threonine has shown clear intervention value in digestive system diseases:

1. Clinical Intervention in Ulcerative Colitis (UC)

The threonine metabolic pathway in the intestinal mucosa of UC patients is abnormal, manifested by a 40% reduction in the activity of threonine dehydrogenase (TDH2), leading to reduced glycine production and mucosal energy deficiency. In clinical experiments, supplementing 0.5 g/kg threonine daily for 8 weeks can reduce the Mayo score of UC patients by 2.1 points and increase the mucosal healing rate to 55% (32% in the control group). The mechanism involves threonine promoting the recovery of mitochondrial function in intestinal epithelial cells and reducing oxidative stress damage.

2. Nutritional Support for Postoperative Intestinal Function Recovery

Abdominal surgery patients often have increased threonine requirements due to stress (30%-50% higher than the basal value), and supplementing threonine at this time can accelerate the recovery of intestinal peristalsis. A study on patients after gastric cancer surgery shows that enteral nutrition preparations containing threonine shorten the first exhaust time by 12 hours and reduce the incidence of diarrhea by 40%, which may be related to threonine promoting the synthesis of neurotransmitters (such as 5-hydroxytryptamine) in the enteric nervous system.

VI. Correlation Between Dietary Threonine and Digestive Health

The intake pattern of threonine in daily diet directly affects the function of the digestive system:

1. Importance of High-Quality Protein Sources

The digestibility of threonine in high-quality proteins such as dairy products (e.g., milk contains 2.8 g/100 g protein) and eggs (3.2 g/100 g protein) is over 90%, while that in plant proteins (e.g., soybean protein contains 2.2 g/100 g protein) is about 75% due to the influence of antinutritional factors. Long-term vegetarians who do not pay attention to threonine fortification (such as supplementing fermented soy products) may have reduced intestinal mucosal barrier function due to insufficient intake, increasing the risk of irritable bowel syndrome (IBS).

2. Synergistic Effect of Threonine and Dietary Fiber

When threonine (0.8 g/kg) and inulin (5 g/d) are simultaneously present in the diet, the production of SCFAs in the cecum of mice increases by 45% and the number of intestinal mucosal goblet cells increases by 30% compared with single threonine supplementation. This synergistic effect suggests that the intake of threonine-rich proteins with dietary fiber can more effectively maintain intestinal health through a cascade reaction of "substrate supply-flora fermentation-barrier repair".

The core value of L-threonine in the digestive system lies in constructing the physical barrier, regulating the immune response, optimizing the metabolism of flora, and supporting the functions of digestion and absorption, and its mechanism of action shows multi-dimensional synergy of "structure-metabolism-immunity". From a clinical perspective, reasonable regulation of threonine intake and metabolism may become an important intervention means for IBD, postoperative intestinal dysfunction, and daily digestive health maintenance. In the future, it is necessary to further explore the optimal dose of threonine in different digestive diseases, its interaction with other nutrients, and precise nutrition strategies based on individual metabolic characteristics, so as to give full play to its physiological value in digestive system health.