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Graphical abstract Highlights • Bacterial extracts from probiotics species modulate human immune response. • The bacterial DNA was the most immunogenic fraction. • The DNA induce a Th17-like response in human PBMCs. • Bacterial fractions can be used to modulate the immune response to improve the gut barrier. Abstract Probiotics are used to improve human health due to their capability to induce beneficial effects in gastrointestinal diseases and modulate the immune response. However, scarce information is known about the bacterial active compounds and the metabolic pathways of interaction with immune cells. In the present study, we analyzed the immune response elicited by surface-associated proteins, the whole surface extract (WSE) and the genomic DNA of three strains from the main representative probiotic species for human consumption, L. acidophilus DSM20079T, L. rhamnosus GG, B. longum NCIMB 8809, using an in vitro model of human PBMCs from healthy donors. Eighteen cytokines were quantified using Luminex Technology to understand the immune pathways modulate by bacterial extracts. Overall, the bacterial fractions elicited a different immune response in PBMCs, whereas the isolated DNA was able to induce a higher Th17-like response that could lead to a protective effect in the epithelial barrier function. [ABSTRACT FROM AUTHOR]

Abstract: Background: Chronic heart failure (CHF) is characterized by an inflammatory status with high levels of cytokines such as IL-6. We hypothesized that patients with CHF may develop immunosenescence due to inflammation and that this may be associated with a worse stage of the disease. Methods and results: We compared the immunological features of 58 elderly CHF patients (ECHF), 40 young CHF patients (YCHF), 60 healthy elderly controls (HEC) and 40 healthy young controls (HYC). We characterized leukocyte and lymphocyte subpopulations by flow cytometry, and IL-6 concentration by ELISA. The extent of CHF was classified according to functional and/or morphological criteria: New York Heart Association functional class, AHA/ACC heart failure stages, left ventricular ejection fraction, and left ventricular hypertrophy. CHF patients showed an increased number of leukocytes, neutrophils and monocytes, but a decreased number of lymphocytes. CHF patients had significantly lower levels of B-cells and CD4+ T-cells, increased NK-cells in YCHF, and increased CD8+ T-cells only in ECHF. CHF was associated with high differentiation in CD4+ and CD8+ T-lymphocyte subsets. Aging of T-lymphocyte subpopulations and high IL-6 levels were associated with a worse clinical status. IL-6 also correlated positively with the number of highly differentiated T-lymphocytes and with their accelerated aging. Conclusions: We conclude that CHF patients show a higher degree of immunosenescence than age-matched healthy controls. T-lymphocyte differentiation and IL-6 levels are increased in patients with an advanced clinical status and may contribute to disease impairment through a compromised adaptive immune response due to accelerated aging of their immune system. [Copyright &y& Elsevier]

• Gut metaproteome is reservoir for encrypted immunomodulatory peptides. • These peptides can modulate the host immune response. • Some of these peptides, such as HM14, exert anti-inflammatory effects. This work supports the massive presence of potential immunomodulatory peptides in the human gut metaproteome. These peptides were identified through the MAHMI database as potentially anti-inflammatory, and sixteen of them synthesized for characterize their mechanism of action. From them, peptide HM14 was encrypted in an extracellular protein produced by Bifidobacterium longum , a common member of the human microbiota, and displayed the highest anti-inflammatory capability. Molecular mechanism of action of HM14 pointed to a specific interaction between this immunomodulatory peptide and antigen presenting cells, which resulted in a higher formation of iTreg cells. Moreover, HM14 was effective in decreasing pro-inflammatory parameters in PBMCs isolated from a cohort of Crohn's patients. Finally, non-targeted metabolomics confirmed the ability of HM14 to modulate the metabolic activity of PBMCs to fulfil its energy and biosynthetic requirements. Overall, our combined in silico /multiomics approach supports the human gut metaproteome as a source for immunomodulatory peptides. [ABSTRACT FROM AUTHOR]

• Crohn's disease is associated with gut microbiota dysbiosis. • Use of probiotic compounds has been proposed to modulate the host immune response. • There is a lack of information on the interaction probiotics-immune system. • Extracellular protein fraction of L. acidophilus exerts anti-inflammatory effects. Lactobacillus genus includes both probiotic and representative strains of the human gut microbiota. Independent studies have reported on the anti-inflammatory properties of different Lactobacillus strains, although we are far from understanding the underlying molecular interplay. In this work we show that a daily administration of Lactobacillus acidophilus DSM20079T (DSM20079) to healthy piglets resulted in plasmatic increases of the anti-inflammatory IL10, whilst IL12 and the pro-inflammatory ratio IL12+TNFα/IL10 decreased. The extracellular protein fraction of DSM20079 was identified as the responsible for the crosstalk interaction that elicited these tolerogenic effects. This strain was able to activate innate immune pathways in dendritic cells and to decrease the production of pro-inflammatory cytokines in both CD4+/CD8+ T cell subsets in healthy donors and in Crohn's Disease patients. The tolerogenic effect exerted by the extracellular proteins of this strain suggests their potential use as coadjutant for therapeutic applications targeting chronic inflammatory illnesses. [ABSTRACT FROM AUTHOR]