The Influence of Dietary Protein Intake on Mammalian Tryptophan and Phenolic Metabolites

Abstract

Although there has been increasing interest in the use of high protein diets, little is known about dietary protein related changes in the mammalian metabolome. We investigated the influence of protein intake on selected tryptophan and phenolic compounds, derived from both endogenous and colonic microbial metabolism. Furthermore, potential inter-species metabolic differences were studied. For this purpose, 29 healthy subjects were allocated to a high (n = 14) or low protein diet (n = 15) for 2 weeks. In addition, 20 wild-type FVB mice were randomized to a high protein or control diet for 21 days. Plasma and urine samples were analyzed with liquid chromatography–mass spectrometry for measurement of tryptophan and phenolic metabolites. In human subjects, we observed significant changes in plasma level and urinary excretion of indoxyl sulfate (P 0.004 and P 0.001), and in urinary excretion of indoxyl glucuronide (P 0.01), kynurenic acid (P 0.006) and quinolinic acid (P 0.02). In mice, significant differences were noted in plasma tryptophan (P 0.03), indole-3-acetic acid (P 0.02), p-cresyl glucuronide (P 0.03), phenyl sulfate (P 0.004) and phenylacetic acid (P 0.01). Thus, dietary protein intake affects plasma levels and generation of various mammalian metabolites, suggesting an influence on both endogenous and colonic microbial metabolism. Metabolite changes are dissimilar between human subjects and mice, pointing to inter-species metabolic differences with respect to protein intake.

Indoxyl Sulfate—Review of Toxicity and Therapeutic Strategies

“…As indoxyl sulfate is derived from breakdown of tryptophan, higher dietary protein intake increases its production. Subjects with normal kidney function who consumed a high protein diet for 2 weeks had greater indoxyl sulfate level and urinary excretion than those who consumed a low protein diet [27]. In addition, subjects who consumed vegetarian diets had lower indoxyl sulfate excretion than those consuming an unrestricted diet with higher protein content [28].…”

“…Because indoxyl sulfate is derived from tryptophan, its production increases with higher dietary protein intake [27,28]. One means to reduce production is therefore to restrict protein intake.…”

Uremic Solutes in Chronic Kidney Disease and Their Role in Progression

“…[18] Uremic solute concentrations were determined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) as described previously. [22] Before chromatography an aliquot of plasma was diluted in H2O (1:1) and deproteinized with perchloric acid (final concentration 3.3% (v/v)). Next, samples were centrifuged at 12,000 x g for 3 min and the clear supernatant was injected into the UPLC-MS/MS system that consisted of an Accela HPLC system coupled to a TSQ Vantage triple quadropole mass spectrometer (Thermo Fischer Scientific, Breda, the Netherlands) equipped with a C18 UPLC column (Acquity UPLC HSS T3 1.8 um; Waters, Milford, MA).…”

The cross-talk between the kidney and the gut: implications for chronic kidney disease

“…The type and amount of substrate, and especially the ratio between undigested carbohydrates and proteins, are the key modulators of bacterial composition and metabolism. When the carbohydrate/protein ratio is reduced, the fermentation of proteins is favored over carbohydrates, resulting in an overgrowth of proteolytic species and a decrease in the growth of saccharolytic bacterial species, resulting in changes in the pattern of metabolites produced [33][34][35][36]. In addition to dietary components, other factors can influence gut microbiota composition and metabolism, such as intestinal pH, medication, time of intestinal transit, host genetics, innate and adaptive immunity, and presence of diseases.…”

“…Moreover, the decrease in protein intake may reduce the delivery of amino acids into the colon and the consequent proteolytic fermentation that generates p-cresol and indole. The benefits of decreasing protein intake on colonderived uremic toxins, especially on indoxyl sulfate (IS), were demonstrated in healthy subjects [36] and CKD patients [127]. Most importantly, the colonic balance between dietary protein and fiber appears to be more relevant in the reduction of serum p-cresyl sulfate (PCS) and IS than the protein intake alone [127][128][129].…”