RESUMO
Candida albicans cell wall component ß-glucan has been extensively studied for its ability to induce epigenetic and functional reprogramming of innate immune cells, a process termed trained immunity. We show that a high-complexity blend of two individual ß-glucans from Saccharomyces cerevisiae possesses strong bioactivity, resulting in an enhanced trained innate immune response by human primary monocytes. The training required the Dectin-1/CR3, TLR4, and MMR receptors, as well as the Raf-1, Syk, and PI3K downstream signaling molecules. By activating multiple receptors and downstream signaling pathways, the components of this ß-glucan preparation are able to act synergistically, causing a robust secondary response upon an unrelated challenge. In in-vivo murine models of melanoma and bladder cell carcinoma, pre-treatment of mice with the ß-glucan preparation led to a significant reduction in tumor growth. These insights may aid in the development of future therapies based on ß-glucan structures that induce an effective trained immunity response.
Assuntos
Saccharomyces cerevisiae , beta-Glucanas , Humanos , Animais , Camundongos , Imunidade Treinada , beta-Glucanas/farmacologia , Monócitos , Transdução de SinaisRESUMO
Background: Histamine intolerance manifests when there is an imbalance between the production of histamine and the body's capacity to metabolise it. Within the gastrointestinal tract, diamine oxidase (DAO) plays a pivotal role in breaking down ingested histamine. Insufficient levels of DAO have been linked to various diseases affecting the respiratory, cardiovascular, nervous, muscular, and digestive systems; some of these symptoms are evidenced in fibromyalgia syndrome. This underscores the crucial role of DAO in maintaining the histamine balance and highlights its association with diverse physiological systems and health conditions. The management of fibromyalgia commonly involves the use of psychotropic medications; however, their potential interactions with DAO remain not fully elucidated. Methods: This study delved into the influence of various psychotropic medications on DAO activity through in vitro experiments. Additionally, we explored their impact on the human intestinal cell line Caco-2, examining alterations in DAO expression at both the mRNA and protein levels along with DAO activity. Results: Notably, the examined drugs-sertraline, pregabalin, paroxetine, alprazolam, and lorazepam-did not exhibit inhibitory effects on DAO activity or lead to reductions in DAO levels. In contrast, citalopram demonstrated a decrease in DAO activity in in vitro assays without influencing DAO levels and activity in human enterocytes. Conclusions: These findings imply that a collaborative approach involving psychotropic medications and DAO enzyme supplementation for individuals with fibromyalgia and a DAO deficiency could offer potential benefits for healthcare professionals in their routine clinical practice.
RESUMO
Long-chain dextrans are α-glucans that can be produced by lactic acid bacteria. NextDextTM, a specific long-chain dextran with a high degree of polymerisation, produced using Weissella cibaria, was recently shown to exert prebiotic potential in vitro. In this study, the ex vivo SIFR® technology, recently validated to provide predictive insights into gut microbiome modulation down to the species level, was used to investigate the effects of this long-chain dextran on the gut microbiota of six human adults that altogether covered different enterotypes. A novel community modulation score (CMS) was introduced based on the strength of quantitative 16S rRNA gene sequencing and the highly controlled ex vivo conditions. This CMS overcomes the limitations of traditional α-diversity indices and its application in the current study revealed that dextran is a potent booster of microbial diversity compared to the reference prebiotic inulin (IN). Long-chain dextran not only exerted bifidogenic effects but also consistently promoted Bacteroides spp., Parabacteroides distasonis and butyrate-producing species like Faecalibacterium prausnitzii and Anaerobutyricum hallii. Further, long-chain dextran treatment resulted in lower gas production compared to IN, suggesting that long-chain dextran could be better tolerated. The additional increase in Bacteroides for dextran compared to IN is likely related to the higher propionate:acetate ratio, attributing potential to long-chain dextran for improving metabolic health and weight management. Moreover, the stimulation of butyrate by dextran suggests its potential for improving gut barrier function and inflammation. Overall, this study provides a novel tool for assessing gut microbial diversity ex vivo and positions long-chain dextran as a substrate that has unique microbial diversity enhancing properties.