Gut microbiota-derived propionate reduces cancer cell proliferation in the liver

Peer reviewedPublisher PD

SCFAs Induce Mouse Neutrophil Chemotaxis through the GPR43 Receptor

Short chain fatty acids (SCFAs) have recently attracted attention as potential mediators of the effects of gut microbiota on intestinal inflammation. Some of these effects have been suggested to occur through the direct actions of SCFAs on the GPR43 receptor in neutrophils, though the precise role of this receptor in neutrophil activation is still unclear. We show that mouse bone marrow derived neutrophils (BMNs) can chemotax effectively through polycarbonate filters towards a source of acetate, propionate or butyrate. Moreover, we show that BMNs move with good speed and directionality towards a source of propionate in an EZ-Taxiscan chamber coated with fibrinogen. These effects of SCFAs were mimicked by low concentrations of the synthetic GPR43 agonist phenylacetamide-1 and were abolished in GPR43−/− BMNs. SCFAs and phenylacetamide-1 also elicited GPR43-dependent activation of PKB, p38 and ERK and these responses were sensitive to pertussis toxin, indicating a role for Gi proteins. Phenylacetamide-1 also elicited rapid and transient activation of Rac1/2 GTPases and phosphorylation of ribosomal protein S6. Genetic and pharmacological intervention identified important roles for PI3Kγ, Rac2, p38 and ERK, but not mTOR, in GPR43-dependent chemotaxis. These results identify GPR43 as a bona fide chemotactic receptor for neutrophils in vitro and start to define important elements in its signal transduction pathways

Dietary Supplementation with Probiotics Improves Hematopoiesis in Malnourished Mice

BACKGROUND: Lactobacillus rhamnosus CRL1505 (Lr) administered during the repletion of immunocompromised-malnourished mice improves the resistance against intestinal and respiratory infections. This effect is associated with an increase in the number and functionality of immune cells, indicating that Lr could have some influence on myeloid and lymphoid cell production and maturation. OBJECTIVE: This study analyzed the extent of the damage caused by malnutrition on myeloid and lymphoid cell development in the spleen and bone marrow (BM). We also evaluated the impact of immunobiotics on the recovery of hematopoiesis affected in malnourished mice. METHODS: Protein malnourished mice were fed on a balanced conventional diet for 7 or 14 consecutive d with or without supplemental Lr or fermented goat's milk (FGM). Malnourished mice and well-nourished mice were used as controls. Histological and flow cytometry studies were carried out in BM and spleen to study myeloid and lymphoid cells. RESULTS: Malnutrition induced quantitative alterations in spleen B and T cells; however, no alteration was observed in the ability of splenic B cells to produce immunoglobulins after challenge with LPS or CpG. The analysis of BM B cell subsets based on B220, CD24, IgM and IgD expression showed that malnutrition affected B cell development. In addition, BM myeloid cells decreased in malnourished mice. On the contrary, protein deprivation increased BM T cell number. These alterations were reverted with Lr or FGM repletion treatments since normal numbers of BM myeloid, T and B cells were observed in these groups. CONCLUSIONS: Protein malnutrition significantly alters B cell development in BM. The treatment of malnourished mice with L. rhamnosus CRL1505 was able to induce a recovery of B cells that would explain its ability to increase immunity against infections. This work highlights the possibility of using immunobiotics to accelerate the recovery of lymphopoyesis in immunocompromised-malnourished hosts

Determination of the prebiotic activity of wheat arabinogalactan peptide (AGP) using batch culture fermentation

Purpose To test the prebiotic activity of wheat arabinogalactan-peptide (AGP), which is a soluble dietary fibre composed of arabinogalactan polysaccharide linked to a 15-residue peptide, which accounts for up to 0.4% of the dry weight of wheat flour. Methods The prebiotic activity of AGP prepared from white wheat flour was tested using in-vitro fermentation by colonic bacteria in automated pH controlled anaerobic stirred batch cultures and compared to fructooligosaccharide (FOS) and wheat flour arabinoxylan (AX). Bacterial populations were measured using fluorescence in-situ hybridisation (flow-FISH) and short-chain fatty acid (SCFA) concentrations were measured using HPLC. Results Fermentation of AGP resulted in a significant bifidogenic activity and increased concentrations of SCFAs, mainly acetate after 24 h of fermentation. Conclusions These results were comparable to those obtained with AX and confirm the prebiotic potential of AGP. Furthermore, fermentation of a mixture of AGP and AX was faster compared to the single substrates and more similar to FOS, indicating that combinations of fermentable carbohydrates with different structures are potentially more effective as prebiotics than single substrates

An in vitro approach to study effects of prebiotics and probiotics on the faecal microbiota and selected immune parameters relevant to the elderly

The aging process leads to alterations of gut microbiota and modifications to the immune response, such changes may be associated with increased disease risk. Prebiotics and probiotics can modulate microbiome changes induced by aging; however, their effects have not been directly compared. The aim of this study was to use anaerobic batch culture fermenters to assess the impact of various fermentable carbohydrates and microorganisms on the gut microbiota and selected immune markers. Elderly volunteers were used as donors for these experiments to enable relevance to an aging population. The impact of fermentation supernatants on immune markers relevant to the elderly were assessed in vitro. Levels of IL-1β, IL-6, IL-8, IL-10 and TNF-α in peripheral blood mononuclear cell culture supernatants were measured using flow cytometry. Trans-galactooligosaccharides (B-GOS) and inulin both stimulated bifidobacteria compared to other treatments (p<0.05). Fermentation supernatants taken from faecal batch cultures supplemented with B-GOS, inulin, B. bifidum, L. acidophilus and Ba. coagulans inhibited LPS induced TNF-α (p<0.05). IL-10 production, induced by LPS, was enhanced by fermentation supernatants from faecal batch cultures supplemented with B-GOS, inulin, B. bifidum, L. acidophilus, Ba. coagulans and Bac. thetaiotaomicron (p<0.05). To conclude, prebiotics and probiotics could lead to potentially beneficial effects to host health by targeting specific bacterial groups, increasing saccharolytic fermentation and decreasing inflammation associated with aging. Compared to probiotics, prebiotics led to greater microbiota modulation at the genus level within the fermenters

Gut-central nervous system axis is a target for nutritional therapies

Historically, in the 1950s, the chemist Linus Pauling established a relationship between decreased longevity and obesity. At this time, with the advent of studies involving the mechanisms that modulate appetite control, some researchers observed that the hypothalamus is the "appetite centre" and that peripheral tissues have important roles in the modulation of gut inflammatory processes and levels of hormones that control food intake. Likewise, the advances of physiological and molecular mechanisms for patients with obesity, type 2 diabetes mellitus, inflammatory bowel diseases, bariatric surgery and anorexia-associated diseases has been greatly appreciated by nutritionists. Therefore, this review highlights the relationship between the gut-central nervous system axis and targets for nutritional therapies