Short-chain fatty acids inhibit the activation of T lymphocytes and myeloid cells and induce innate immune tolerance.

The intestinal microbiota contributes to gut immune homeostasis, where short-chain fatty acids (SCFAs) function as the major mediators. We aimed to elucidate the immunomodulatory effects of acetate, propionate, and butyrate. With that in mind, we sought to characterise the expression of SCFA receptors and transporters as well as SCFAs' impact on the activation of different immune cells. Whereas all three SCFAs decreased tumour necrosis factor (TNF)-α production in activated T cells, only butyrate and propionate inhibited interferon (IFN)-γ, interleukin (IL)-17, IL-13, and IL-10 production. Butyrate and propionate inhibited the expression of the chemokine receptors CCR9 and CCR10 in activated T- and B-cells, respectively. Similarly, butyrate and propionate were effective inhibitors of IL-1ß, IL-6, TNF-α, and IL-10 production in myeloid cells upon lipopolysaccharide and R848 stimulation. Acetate was less efficient at inhibiting cytokine production except for IFN-α. Moreover, SCFAs inhibited the production of IL-6 and TNF-α in monocytes, myeloid dendritic cells (mDC), and plasmacytoid dendritic cells (pDC), whereas acetate effects were relatively more prominent in pDCs. In monocytes and mDCs, acetate was a less efficient inhibitor, but it was equally effective in inhibiting pDCs activation. We also studied the ability of SCFAs to induce trained immunity or tolerance. Butyrate and propionate - but not acetate - prevented Toll-like receptor-mediated activation in SCFA-trained cells, as demonstrated by a reduced production of IL-6 and TNF-α. Our findings indicate that butyrate and propionate are equally efficient in inhibiting the adaptive and innate immune response and did not induce trained immunity. The findings may be explained by differential SCFA receptor and transporter expression profiles of the immune cells.

Hydrolysates of glycated and heat-treated peanut 7S globulin (Ara h 1) modulate human gut microbial proliferation, survival and adhesion.

AIMS: Evaluation of an effect of glycation of Ara h 1 on proliferation and survival rate and adhesion of intestinal Enterococcus faecalis, Escherichia coli and Lactobacillus acidophilus. METHODS AND RESULTS: Pure Ara h 1 heated at three different temperature conditions (G37, G60 and C145°C) in the presence or absence of glucose was subjected to enzymatic hydrolysis. Impacts of Ara h 1 hydrolysates on the bacterial proliferation, survival rate and adhesion to Caco-2 cells in mono and heterogeneous cultures were studied with fluorescent techniques: DAPI, LIVE/DEAD staining and FISH. Examined hydrolysates hindered proliferation of E. coli and Ent. faecalis with simultaneous decrease in their survival. Maillard reaction (MR, glycation) of Ara h 1 did not alter the effect of hydrolysates on bacterial proliferation rate. Hydrolysates modified at 60 and 145°C with glucose altered the profile of immobilized bacteria, mostly by lowering the number of adhering E. coli and promoting the adhesion of bacteria from genera Lactobacillus and Enterococcus. CONCLUSIONS: Ara h1 hydrolysates processed in various ways demonstrated their strong modulatory effect on bacterial proliferation, survival rate and adhesion. SIGNIFICANCE AND IMPACT OF THE STUDY: Reducing the adhesion of opportunistic bacteria by hydrolysates of Ara h 1 glycated at 60 and 145°C, together with modulation of immobilization of beneficial lactobacilli and enterococci, may be of relevance in terms of the physiological status of the intestinal barrier.