Recent evidence suggests that tryptophan, an essential amino acid, may exert biological effects by means of tryptophan-derived gut bacteria products. We evaluated the potential contribution of tryptophan-derived bacterial metabolites to body weight gain. The study comprised three experimental series performed on separate groups of male, Sprague-Dawley rats: (i) rats on standard laboratory diet treated with water solution of neomycin, an antibiotic, or tap water (controls-1); (ii) rats on standard diet (controls-2) or tryptophan-high (TH) or tryptophan-free (TF) diet; and (iii) rats treated with indole-3-propionic acid (I3P), a bacterial metabolite of tryptophan, or a vehicle (controls-3). (i) Rats treated with neomycin showed a significantly higher weight gain but lower stool and blood concentration of I3P than controls-1. (ii) The TH group showed significantly smaller increases in body weight but higher stool and plasma concentration of I3P than controls-2. In contrast, the TF group showed a decrease in body weight, decreased total serum protein and a significant increase in urine output. (iii) Rats treated with I3P showed significantly smaller weight gain than controls-3. Our study suggests that I3P, a gut bacteria metabolite of tryptophan, contributes to changes in body weight gain produced by antibiotics and tryptophan-rich diet.

Portal hypertension (PH) is a potentially life-threatening condition. We investigated the effects of indole and dietary tryptophan, a substrate for gut bacterial production of indole, on portal blood pressure (PBP), portal blood flow (PBF), and arterial blood pressure (ABP) in Sprague-Dawley rats (SD) and SD with PH induced by liver cirrhosis (SD-PH). Hemodynamics were recorded in anesthetized male 28-wk-old SD and SD-PH at baseline and after the administration of either a vehicle or indole into the colon. Blood levels of tryptophan and its bacterial metabolites were evaluated using chromatography coupled with mass spectrometry. Indole at lower doses increased PBP and PBF. Indole at higher doses produced a transient increase in PBP, which was accompanied by a decrease in ABP. Portal blood levels of indole, indole-3-propionic, indole-3-lactic, and indole-3-acetic acids were higher in SD-PH, suggesting an increased gut-blood barrier permeability. Rats on a tryptophan-rich diet showed a significantly higher PBP and portal blood level of indoles than rats on a tryptophan-free diet. In conclusion, a tryptophan-rich diet and intracolonic indole increase PBP and portal blood level of indole. Rats with PH show an increased penetration of indoles from the colon to the circulation. Intracolonic indole production may be of therapeutic importance in PH.

Recent evidence suggests that gut bacteria-derived metabolites interact with the cardiovascular system and alter blood pressure (BP) in mammals. Here, we evaluated the effect of indole-3-propionic acid (IPA), a gut bacteria-derived metabolite of tryptophan, on the circulatory system. Arterial BP, electrocardiographic, and echocardiographic (ECHO) parameters were recorded in male, anesthetized, 12-wk-old Wistar-Kyoto rats at baseline and after intravenous administration of either IPA or vehicle. In additional experiments, rats were pretreated with prazosin or pentolinium to evaluate the involvement of the autonomic nervous system in cardiovascular responses to IPA. IPA’s concentrations were measured using ultra-high performance liquid chromatography tandem mass spectrometry. The reactivity of endothelium-intact and -denuded mesenteric resistance arteries was tested. Cells’ viability and lactate dehydrogenase (LDH) cytotoxicity assays were performed on cultured cardiomyocytes. IPA increased BP with a concomitant bradycardic response but no significant change in QTc interval. The pretreatment with prazosin and pentolinium reduced the hypertensive response. ECHO showed increased contractility of the heart after the administration of IPA. Ex vivo, IPA constricted predilated and endothelium-denuded mesenteric resistance arteries and increased metabolic activity of cardiomyocytes. IPA increases BP via cardiac and vascular mechanisms in rats. Furthermore, IPA increases cardiac contractility and metabolic activity of cardiomyocytes. Our study suggests that IPA may act as a mediator between gut microbiota and the circulatory system.

Numerous formulations derived from the shiitake medicinal mushroom, Lentinus edodes, demonstrate anticancer activities. We hypothesized that isolates from selenium (Se)-enriched mycelia of L. edodes would possess stronger cancer-preventive properties than current preparations. The aim of this study was to investigate whether the presence of Se-methyl-seleno-L-cysteine in mycelial extracts of L. edodes affects their cytotoxic activity (makes them stronger) or whether they are as effective as Se-containing polysaccharides. Extracts were prepared from Se-containing mycelia under various conditions and assayed for cytotoxic activity in cancer (PC3 and HeLa) and normal (HMEC-1) cell lines. The chemical composition of the extracts was examined; specifically, the amounts of potentially cytotoxic Se compounds (methylselenocysteine, selenomethionine, and Se-containing polysaccharides) were measured. The relationship between extract composition and biological activity was characterized. Mycelial cultures were cultivated in a 10-L bioreactor in medium enriched with sodium selenite. Mycelial extracts were prepared either at 100°C or at 4°C in acidic solution. Total Se content was determined using the atomic absorption spectrometry method, and methylselenocysteine and selenomethionine contents were measured using reverse-phase high-performance liquid chromatography. Protein, carbohydrate, and polyphenolic contents were determined with spectrophotometric methods, and Se-containing polysaccharides were measured with the use of precipitation. Anticancer activity of mycelial extracts was examined using the MTT cell viability assay. Extracts containing Se-methyl-seleno-L-cysteine or Se-polysaccharides prepared at 4°C and 100°C, respectively, display moderate, time-dependent, specific cytotoxic activity in HeLa and PC3 cell lines. The effect in HeLa cells is more pronounced in the extract prepared at 4°C than at 100°C. The effect is almost equal for the PC3 cell line. However, both extracts have no effect or only slightly stimulate normal (HMEC-1) cell viability. The selective cytotoxic activity of L. edodes extracts in cancer (PC3 and HeLa) cells is due to the presence of both Se-methyl-seleno-L-cysteine and selenated polysaccharides, perhaps in combination with other active ingredients.

Selenium–polysaccharides possess antioxidant properties, making them promising materials for functional foods, pharmaceuticals, and clinical applications. This study examines the incorporation of selenium into polysaccharides via mycelial biosynthesis and its effects on structure and antioxidant activity. Polysaccharides obtained from Lentinula edodes-submerged cultures grown in Se-supplemented and non-supplemented media were analysed for Se content (RP-HPLC/FLD), structure (FT-IR, HPLC, and HPGPC-ELSD), and antioxidant activity (DPPH scavenging, reducing power, and Fe²⁺ chelation). Two low-molecular-weight Se–heteropolysaccharides (Se-FE-1.1 and Se-FE-1.2) containing ~80 and 125 µg/g Se were isolated, primarily composed of glucose, mannose, and galactose with β-glycosidic linkages. Se incorporation into polysaccharides selectively enhanced their antioxidant activity in the DPPH radical scavenging assay, with minimal effects observed in iron chelation and reducing power assays. Crude Se–polysaccharides displayed the highest antioxidant activity, suggesting an additional contribution from protein components. Our findings demonstrate that Se is effectively incorporated into polysaccharides, altering monosaccharide composition while preserving glycosidic linkages. The selective enhancement of radical scavenging suggests that selenium plays a specific role in antioxidant activity, primarily influencing radical scavenging mechanisms rather than interactions with metal ions. Further research is needed to clarify the mechanisms of selenium incorporation, the nature of its bonding within the polysaccharide molecule, and its impact on biological activity.