scholarly journals Lactic Acid-Producing Probiotic Saccharomyces cerevisiae Attenuates Ulcerative Colitis via Suppressing Macrophage Pyroptosis and Modulating Gut Microbiota

2021 ◽  
Vol 12 ◽  
Author(s):  
Siyuan Sun ◽  
Xiuxiu Xu ◽  
Ling Liang ◽  
Xiaoli Wang ◽  
Xue Bai ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Ulcerative Colitis ◽  
Lactic Acid ◽  
Intestinal Microbiota ◽  
Macrophage Polarization ◽  
Polarization State ◽  
Mucosal Barrier ◽  
Acid Uptake ◽  
Signal Molecule

Lactic acid, a metabolic by-product of host and intestinal microbiota, has been recovered as an active signal molecule in the immune system. In this study, a lactic acid biosynthesis pathway that directly produces lactic acid from glucose rather than ethanol with high production was reconstructed in Saccharomyces cerevisiae. The engineered S. cerevisiae showed anti-inflammatory activity in dextran sulfate sodium (DSS)-induced mice with improved histological damage, increased mucosal barrier, and decreased intestinal immune response. Lactic acid regulated the macrophage polarization state and inhibited the expression of pro-inflammatory cytokines in vivo and in vitro. Increasing the macrophage monocarboxylic acid transporter-mediated active lactic acid uptake suppressed the excessive activation of the NLRP3 inflammasome and the downstream caspase-1 pathway in macrophages. Moreover, lactic acid promoted histone H3K9 acetylation and histone H3K18 lactylation. Meanwhile, the engineered S. cerevisiae altered the diversity and composition of the intestinal microbiota and changed the abundance of metabolic products in mice with colitis. In conclusion, this study shows that the application of engineered S. cerevisiae attenuated DSS-induced colitis in mice via suppressing macrophage pyroptosis and modulating the intestinal microbiota, which is an effective and safe treatment strategy for ulcerative colitis.

Use of Synbiotics for Ulcerative Colitis Treatment

2020 ◽  
Vol 15 (3) ◽  
pp. 174-182 ◽  
Author(s):  
Marianna Roselli ◽  
Alberto Finamore
Keyword(s):  
Ulcerative Colitis ◽  
Gastrointestinal Tract ◽  
Intestinal Microbiota ◽  
Strong Impact ◽  
Beneficial Effects ◽  
System A ◽  
Bowel Diseases ◽  
Ulcerative Colitis Treatment ◽  
Inflammatory Bowel

Inflammatory bowel diseases, namely Crohn's disease and ulcerative colitis, are currently considered multifactorial pathologies in which various combined environmental factors act on genetic background, giving rise to chronic inflammation of the gastrointestinal tract. Ulcerative colitis is an inflammation of the colon caused by a dysregulated immune response to host intestinal microbiota in genetically susceptible subjects. Ulcerative colitis has a strong impact on patients' quality of life, as well as high costs for the health-care system. A great interest on the role of intestinal microbiota modulation in ulcerative colitis is emerging. Several studies have shown an improvement of inflammatory markers and symptoms in ulcerative colitis patients through treatments with probiotics and prebiotics separately. Despite the low number of studies on the treatment of ulcerative colitis by specific strains of probiotics plus selected prebiotics, i.e. synbiotics, the results are promising, even if discordant. The mechanism of action in synbiotics supplementation is still unclear and needs more investigation, although there is a large number of data indicating that the synergism between probiotics and prebiotics favours the survival and implantation of probiotics into the gastrointestinal tract with beneficial effects on human health by modulating the inflammatory response and gut microbiota composition. The aim of this minireview is to describe the main in vitro, animal and human studies performed up to now, that have used synbiotics to treat ulcerative colitis, and to highlight limitations and future perspectives.

scholarly journals Functional expression of the lactate permease Jen1p of Saccharomyces cerevisiae in Pichia pastoris

2003 ◽  
Vol 376 (3) ◽  
pp. 781-787 ◽  
Author(s):  
Isabel SOARES-SILVA ◽  
Dorit SCHULLER ◽  
Raquel P. ANDRADE ◽  
Fátima BALTAZAR ◽  
Fernanda CÁSSIO ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Acetic Acid ◽  
Lactic Acid ◽  
Pichia Pastoris ◽  
Plasma Membranes ◽  
Membrane Vesicle ◽  
Dry Weight ◽  
Functional Expression ◽  
Acid Uptake ◽  
Methanol Induction

In Saccharomyces cerevisiae the activity for the lactate–proton symporter is dependent on JEN1 gene expression. Pichia pastoris was transformed with an integrative plasmid containing the JEN1 gene. After 24 h of methanol induction, Northern and Western blotting analyses indicated the expression of JEN1 in the transformants. Lactate permease activity was obtained in P. pastoris cells with a Vmax of 2.1 nmol·s−1·mg of dry weight−1. Reconstitution of the lactate permease activity was achieved by fusing plasma membranes of P. pastoris methanol-induced cells with Escherichia coli liposomes containing cytochrome c oxidase, as proton-motive force. These assays in reconstituted heterologous P. pastoris membrane vesicles demonstrate that S. cerevisiae Jen1p is a functional lactate transporter. Moreover, a S. cerevisiae strain deleted in the JEN1 gene was transformed with a centromeric plasmid containing JEN1 under the control of the glyceraldehyde-3-phosphate dehydrogenase constitutive promotor. Constitutive JEN1 expression and lactic acid uptake were observed in cells grown on either glucose and/or acetic acid. The highest Vmax (0.84 nmol·s−1·mg of dry weight−1) was obtained in acetic acid-grown cells. Thus overexpression of the S. cerevisiae JEN1 gene in both S. cerevisiae and P. pastoris cells resulted in increased activity of lactate transport when compared with the data previously reported in lactic acid-grown cells of native S. cerevisiae strains. Jen1p is the only S. cerevisiae secondary porter characterized so far by heterologous expression in P. pastoris at both the cell and the membrane-vesicle levels.

scholarly journals Role of LpL (Lipoprotein Lipase) in Macrophage Polarization In Vitro and In Vivo

2019 ◽  
Vol 39 (10) ◽  
pp. 1967-1985 ◽  
Author(s):  
Hye Rim Chang ◽  
Tatjana Josefs ◽  
Diego Scerbo ◽  
Namrata Gumaste ◽  
Yunying Hu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipoprotein Lipase ◽  
Lipid Accumulation ◽  
Macrophage Polarization ◽  
Myeloid Cell ◽  
Acid Uptake ◽  
Lipid Uptake ◽  
Very Low Density Lipoproteins

Objective: Fatty acid uptake and oxidation characterize the metabolism of alternatively activated macrophage polarization in vitro, but the in vivo biology is less clear. We assessed the roles of LpL (lipoprotein lipase)-mediated lipid uptake in macrophage polarization in vitro and in several important tissues in vivo. Approach and Results: We created mice with both global and myeloid-cell specific LpL deficiency. LpL deficiency in the presence of VLDL (very low-density lipoproteins) altered gene expression of bone marrow–derived macrophages and led to reduced lipid uptake but an increase in some anti- and some proinflammatory markers. However, LpL deficiency did not alter lipid accumulation or gene expression in circulating monocytes nor did it change the ratio of Ly6C high /Ly6C low . In adipose tissue, less macrophage lipid accumulation was found with global but not myeloid-specific LpL deficiency. Neither deletion affected the expression of inflammatory genes. Global LpL deficiency also reduced the numbers of elicited peritoneal macrophages. Finally, we assessed gene expression in macrophages from atherosclerotic lesions during regression; LpL deficiency did not affect the polarity of plaque macrophages. Conclusions: The phenotypic changes observed in macrophages upon deletion of Lpl in vitro is not mimicked in tissue macrophages.

scholarly journals In-Vitro Characterization of Growth Inhibition against the Gut Pathogen of Potentially Probiotic Lactic Acid Bacteria Strains Isolated from Fermented Products

2021 ◽  
Vol 9 (10) ◽  
pp. 2141
Author(s):  
Ji Young Jung ◽  
Sang-Soo Han ◽  
Z-Hun Kim ◽  
Myung Hoo Kim ◽  
Hye Kyeong Kang ◽  
...  
Keyword(s):  
Lactic Acid ◽  
Lactic Acid Bacteria ◽  
Intestinal Microbiota ◽  
Cell Surface Hydrophobicity ◽  
16S Rrna Genes ◽  
Rrna Genes ◽  
In Vitro Assays ◽  
The Impact ◽  
Fermented Products

Lactic acid bacteria (LAB) are probiotic candidates that may restore the balance of microbiota populations in intestinal microbial ecosystems by controlling pathogens and thereby promoting host health. The goal of this study was to isolate potential probiotic LAB strains and characterize their antimicrobial abilities against pathogens in intestinal microbiota. Among 54 LAB strains isolated from fermented products, five LAB strains (NSMJ15, NSMJ16, NSMJ23, NSMJ42, and NFFJ04) were selected as potential probiotic candidates based on in vitro assays of acid and bile salt tolerance, cell surface hydrophobicity, adhesion to the intestinal epithelium, and antagonistic activity. Phylogenetic analysis based on 16S rRNA genes showed that they have high similarities of 99.58–100% to Lacticaseibacillus paracasei strains NSMJ15 and NFFJ04, Lentilactobacillus parabuchneri NSMJ16, Levilactobacillus brevis NSMJ23, and Schleiferilactobacillus harbinensis NSMJ42. To characterize their antimicrobial abilities against pathogens in intestinal microbiota, the impact of cell-free supernatant (CFS) treatment in 10% (v/v) fecal suspensions prepared using pooled cattle feces was investigated using in vitro batch cultures. Bacterial community analysis using rRNA amplicon sequencing for control and CFS-treated fecal samples at 8 and 16 h incubation showed the compositional change after CFS treatment for all five LAB strains. The changed compositions were similar among them, but there were few variable increases or decreases in some bacterial groups. Interestingly, as major genera that could exhibit pathogenicity and antibiotic resistance, the members of Bacillus, Escherichia, Leclercia, Morganella, and Vagococcus were decreased at 16 h in all CFS-treated samples. Species-level classification suggested that the five LAB strains are antagonistic to gut pathogens. This study showed the probiotic potential of the five selected LAB strains; in particular, their antimicrobial properties against pathogens present in the intestinal microbiota. These strains would therefore seem to play an important role in modulating the intestinal microbiome of the host.

scholarly journals Primary human macrophages are polarized towards pro-inflammatory phenotypes in alginate hydrogels

2019 ◽  
Author(s):  
Derfogail Delcassian ◽  
Anna A. Malecka ◽  
Donaldson Opoku ◽  
Virginia Palomares Cabeza ◽  
Catherine Merry ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Polarization State ◽  
Fold Increase ◽  
M2 Macrophages ◽  
Human Macrophages ◽  
Culture Systems ◽  
Wide Range ◽  
Alginate Hydrogels ◽  
Planar Substrates

AbstractDysregulated macrophage function is implicated in a wide range of disorders. In vitro hydrogel culture systems are often used as matrices to model and explore the effect of various external stimuli on macrophage polarization and behaviour. Here, we show that 3D alginate hydrogels are not “macrophage inert” and instead help to direct the maturation of primary human macrophages towards specific phenotypes. We compared polarization of M1-like and M2-like cells activated on planar substrates or in 3D alginate hydrogels (with or without adhesion motifs (RGD)). We show that culture in 3D alginate systems selectively alters M2 polarisation following activation; cells show a 2.6-fold increase in CD86 expression compared to cells matured on planar controls, and increase IL1β cytokine secretion even in response to an M2-like stimulus (LPS alone in the absence of IFNγ). Our results suggest that alginate materials may intrinsically stimulate M2 macrophages to acquire a unique polarization state (resembling M2b), characterized by enhanced expression of CD86 and IL1β secretion while retaining low IL12 and high IL10 secretion typical for M2 macrophages. This has important implications for researchers using alginate hydrogels to study macrophage behavior in culture and co-culture systems, as alginate itself may induce direct phenotypic changes independently or in conjunction with other stimuli.

scholarly journals Topical insulin application accelerates diabetic wound healing by promoting anti-inflammatory macrophage polarization

2020 ◽  
Vol 133 (19) ◽  
pp. jcs235838
Author(s):  
Peilang Yang ◽  
Xiqiao Wang ◽  
Di Wang ◽  
Yan Shi ◽  
Meng Zhang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Macrophage Polarization ◽  
Healing Process ◽  
Polarization State ◽  
Wound Healing Process ◽  
Diabetic Wound ◽  
Insulin Degrading Enzyme ◽  
Diabetic Wound Healing ◽  
Diabetic Wounds

ABSTRACTBesides regulating glucose levels, insulin has been reported to participate actively in many other functions, including modulating inflammatory reactions. In this study we investigated how topical insulin application would affect the diabetic wound healing process. We found that the excessive expression of insulin-degrading enzyme led to insufficient insulin levels in diabetic skin during wound healing, which ultimately reduced the recovery rate of diabetic wounds. We confirmed that topical insulin application could reverse the impaired inflammation reaction in the diabetic wound environment and promote healing of diabetic wounds. Our study revealed that insulin promoted apoptosis of neutrophils and subsequently triggered polarization of macrophages. Both in vivo and in vitro studies verified that insulin re-established phagocytosis function and promoted the process of phagocytosis-induced apoptosis in neutrophils. Furthermore, we found that insulin treatment also promoted efferocytosis of the apoptosed neutrophils by macrophages, and thus induced macrophages to change their polarization state from M1 to M2. In conclusion, our studies proved that the exogenous application of insulin could improve diabetic wound healing via the restoration of the inflammatory response.

scholarly journals Rosmarinic acid protects against ulcerative colitis by regulating macrophage polarization depending on heme oxygenase-1 in mice

2020 ◽  
Vol 18 ◽  
pp. 205873922095991
Author(s):  
Ping Mai ◽  
Cheng Chen ◽  
Xiaohui Xiao ◽  
Xin Ma ◽  
Yuping Shi ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Heme Oxygenase ◽  
Rosmarinic Acid ◽  
Molecular Mechanisms ◽  
Macrophage Polarization ◽  
Alternative Activation ◽  
Heme Oxygenase 1 ◽  
Zinc Protoporphyrin ◽  
M1 Polarization

Ulcerative colitis (UC) is an unknown-cause inflammatory disease of colorectum. At present, there are no specific therapeutic drugs. We found that rosmarinic acid (RA) can significantly improve UC and further explored the relevant cellular and molecular mechanisms. Firstly, using F4/80 as marker for mouse macrophages, we found there were large numbers of macrophages infiltrating into colonic tissue of dextran sulfate sodium (DSS)-induced mice UC model. Meanwhile, RA markedly improved weight loss, diarrhea, hematochezia and colonic inflammation in mice with DSS treatment. Further, RA changed macrophage polarization in mouse colon, showing that classical activation (M1) phenotype decreased, alternative activation (M2) phenotype increased, and M1/M2 ratio reversed by Real-time PCR. In vitro, we cultured the peripheral blood macrophages (PBM) and found that RA inhibited PBM M1 polarization and favored M2 polarization directly. Heme oxygenase-1 (HO-1) mediated the anti-inflammatory effect of RA. RA induced HO-1 expression in PBM, and the HO-1 inhibitor, zinc protoporphyrin, blunted the inhibitory effect of RA on lipopolysaccharide (LPS)-induced nuclear factor-kappa B (NF-κB) translocation and M1 polarization. In addition, blocking NF-κB signal has no effect on the role of RA. In conclusion, RA protects against UC by regulating macrophage polarization depending on HO-1. These data suggest that reversing macrophage polarization can be used as a strategy for UC treatment and RA is an effective drug to cure UC by regulating macrophage polarization.

scholarly journals Copper/Zinc-Modified Palygorskite Protects Against Salmonella Typhimurium Infection and Modulates the Intestinal Microbiota in Chickens

2021 ◽  
Vol 12 ◽  
Author(s):  
Chaozheng Zhang ◽  
Dawei Yao ◽  
Zenan Su ◽  
Huan Chen ◽  
Pan Hao ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Intestinal Inflammation ◽  
Antibacterial Properties ◽  
Inhibitory Effect ◽  
Mucosal Barrier ◽  
Serovar Typhimurium ◽  
Copper Zinc ◽  
Modified Palygorskite

Palygorskite (Pal), a clay nanoparticle, has been demonstrated to be a vehicle for drug delivery. Copper has antibacterial properties, and zinc is an essential micronutrient for intestinal health in animals and humans. However, whether copper/zinc-modified Pal (Cu/Zn-Pal) can protect chickens from Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) infection remains unclear. In this study, three complexes (Cu/Zn-Pal-1, Cu/Zn-Pal-2, and Cu/Zn-Pal-3) were prepared, and Cu/Zn-Pal-1 was shown to be the most effective at inhibiting the growth of S. Typhimurium in vitro, whereas natural Pal alone had no inhibitory effect. In vivo, Cu/Zn-Pal-1 reduced S. Typhimurium colonization in the intestine of infected chickens and relieved S. Typhimurium-induced organ and intestinal mucosal barrier damage. Moreover, this reduction in Salmonella load attenuated intestinal inflammation and the oxidative stress response in challenged chickens. Additionally, Cu/Zn-Pal-1 modulated the intestinal microbiota in infected chickens, which was characterized by the reduced abundance of Firmicutes and the increased abundance of Proteobacteria and Bacteroidetes. Our results indicated that the Cu/Zn-Pal-1 complex may be an effective feed supplement for reducing S. Typhimurium colonization of the gut.

scholarly journals Harmine Alleviates Titanium Particle-Induced Inflammatory Bone Destruction by Immunomodulatory Effect on the Macrophage Polarization and Subsequent Osteogenic Differentiation

2021 ◽  
Vol 12 ◽  
Author(s):  
Liangliang Wang ◽  
Qing Wang ◽  
Wei Wang ◽  
Gaoran Ge ◽  
Nanwei Xu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Osteogenic Differentiation ◽  
Macrophage Polarization ◽  
Polarization State ◽  
Bone Destruction ◽  
Wear Particle ◽  
Central Nervous Systems ◽  
The Impact

Peri-prosthetic osteolysis (PPO) and following aseptic loosening are regarded as the prime reasons for implant failure after joint replacement. Increasing evidence indicated that wear-debris-irritated inflammatory response and macrophage polarization state play essential roles in this osteolytic process. Harmine, a β-carboline alkaloid primitively extracted from the Peganum harmala seeds, has been reported to have various pharmacological effects on monoamine oxidase action, insulin intake, vasodilatation and central nervous systems. However, the impact of harmine on debris-induced osteolysis has not been demonstrated, and whether harmine participates in regulating macrophage polarization and subsequent osteogenic differentiation in particle-irritated osteolysis remains unknown. In the present study, we investigated the effect of harmine on titanium (Ti) particle-induced osteolysis in vivo and in vitro. The results suggested harmine notably alleviated Ti particle-induced bone resorption in a murine PPO model. Harmine was also found to suppress the particle-induced inflammatory response and shift the polarization of macrophages from M1 phenotypes to M2 phenotypes in vivo and in vitro, which improved anti-inflammatory and bone-related cytokines levels. In the conditioned medium from Ti particle-stimulated murine macrophage RAW264.7 cells treated with harmine, the osteoblast differentiation ability of mouse pre-osteoblastic MC3T3-E1 cells was greatly increased. And we also provided evidences that the immunomodulatory capacity of harmine might be attributed to the inhibition of the c-Jun N-terminal kinase (JNK) in wear particle-treated macrophages. All the results strongly show that harmine might be a promising therapeutic agent to treat PPO.

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