Willem Zwaan

Daily consumption of 5.0 g  Agaricus bisporus powder for 8 weeks, increased whole blood ergothioneine concentrations, but did not improve vaccination responses following annual influenza vaccination in men and women aged 60 years or older.

Background/Objectives: This study evaluated the immunomodulatory effects of multiple A. bisporus strains, applying both in vitro and in vivo murine models and aiming to identify specific strains with immune modulatory properties. Methods: Sixteen A. bisporus strains were screened in a dendritic cell (DC)–CD4⁺ T cell co-culture system, using cells from female C57BL/6 mice, for their capacity to induce Th1- and Th17-associated cytokine production. Based on these cytokine profiles, three potent strains (MES01856, MES01706, MES01637), one non-responder strain (MES01515), and the commercially available A15 strain were selected for investigation in a murine model, an ovalbumin (OVA)-induced allergic food allergy. In these sensitized female C3H/HeOuJ mice, ear swelling, anaphylactic shock scores, OVA-specific IgE, and serum mouse mast cell protease-1 (mMCP-1) were measured following an allergen challenge. Additionally, IL-6, IL-10, and TNF-α secretion from bone marrow-derived dendritic cells (BMDCs) was measured after stimulation with these A. bisporus fresh ground extracts (FGEs). Results: In vitro, increases in cytokine production were obtained, with MES01856, MES01706, and MES01637 identified as the most potent inducers. In vivo, OVA sensitization elicited significant ear swelling and elevated shock scores in the mice. Dietary supplementation with MES01706 or MES01515 significantly reduced ear swelling, while the other strains resulted in non-significant changes. No significant changes were observed in shock scores, OVA-specific IgE, or mMCP-1. Conclusions: Multiple different A. bisporus strains elicit specific immunomodulating effects both in vitro and in in vivo murine models, identifying the MES01706 strain as one with the highest potential to beneficially affect immune function.

Aging is accompanied by a gradual decline in immune function. Previously, we demonstrated that daily intake of 4 g plant stanols, provided as fatty-acid esters, increased antibody titre responses following different vaccinations. Effects of lower intakes, however, are unknown. We therefore evaluated whether daily consumption of 2, 3 or 4 g of plant stanols, provided as fatty-acid esters, improved immune responses following influenza vaccination in older adults. A double-blind, randomized, placebo-controlled parallel trial was performed. Older participants (59–87 years) consumed products with added plant stanols (2, 3 or 4 g d⁻¹ provided as fatty-acid esters) or control products for approximately 14 days prior to vaccination until 4 weeks post-vaccination. Antibody titres, serum metabolic risk markers, and haematological and immunological parameters were measured and statistically evaluated using linear mixed models. Data of 128 participants were analysed. Changes in IgM and IgG concentrations did not differ significantly between the control and plant stanol groups. Also, changes in Hemagglutination Inhibition (HI) antibody titres were not significantly different between the groups for either the Phuket or Victoria strains. Serum LDL-cholesterol concentrations decreased significantly in the 4 g d⁻¹ and 3 g d⁻¹ groups compared with control. Serum LDL-cholesterol concentrations in the 2 g d⁻¹ group were also lowered, but did not reach statistical significance. No between-group differences in haematological and immunological parameters were observed. Daily consumption of 2, 3 or 4 g of plant stanols provided as fatty-acid esters, did not improve vaccination responses following annual influenza vaccination in men and women aged 60 years or older.

A higher concentration of apolipoprotein A-I (ApoA-I) is associated with increased high density lipoprotein functionality and reverse cholesterol transport (RCT). A promising strategy to prevent cardiovascular diseases is therefore to improve RCT by increasing de novo ApoA-I production. Since experimental animal models have suggested effects of amino acids on hepatic lipoprotein metabolism, we here examined the effects of different amino acids on hepatic ApoA-I production. Human hepatocytes (HepG2) were exposed to six individual amino acids for 48 h. ApoA-I transcription and secreted pro-ApoA-I protein concentrations were analyzed using quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assays (ELISA), respectively. Additionally, CPT1 and KEAP1 mRNA expression, peroxisome proliferator-activated receptor alpha (PPARα) transactivation, and mechanistic target of rapamycin complex 1 (mTORC1) phosphorylation were determined. Leucine, glutamic acid, and tryptophan increased ApoA-I and CPT1 mRNA expression. Tryptophan also strongly increased PPARα transactivation. Glutamine, proline, and histidine increased pro-ApoA-I protein concentrations but mTORC1 phosphorylation remained unchanged regardless of the amino acid provided. In conclusion, individual amino acids have different effects on ApoA-I mRNA expression and pro-ApoA-I production which can partially be explained by specific effects on PPARα transactivation, while mTORC1 phosphorylation remained unaffected.

Apolipoprotein A-I (ApoA-I) is the major protein of high density lipoprotein (HDL) particles and has a crucial role in reverse cholesterol transport (RCT). It has been postulated that elevating production of de novo ApoA-I might translate into the formation of new functional HDL particles that could lower cardiovascular disease (CVD) risk via RCT. During inflammation, serum ApoA-I concentrations are reduced, which contributes to the development of dysfunctional HDL particles as Serum Amyloid A (SAA) overtakes the position of ApoA-I within the HDL particles. Therefore, instead of elevating serum HDL cholesterol concentrations, rescuing lower serum ApoA-I concentrations could be beneficial in both normal and inflamed conditions. Several nutritional compounds, amongst others short chain fatty acids (SCFAs), have shown their capacity to modulate hepatic lipoprotein metabolism. In this review we provide an overview of HDL and more specific ApoA-I metabolism, SCFAs physiology and the current knowledge regarding the influence of SCFAs on ApoA-I expression and synthesis in human liver cells. We conclude that the current evidence regarding the effect of SCFAs on ApoA-I transcription and secretion is promising, however there is a need to investigate which dietary fibres could lead to increased SCFAs formation and consequent elevated ApoA-I concentrations.