How do probiotics alleviate constipation? A narrative review of mechanisms.

Constipation is a common gastrointestinal condition, which may occur at any age and affects countless people. The search for new treatments for constipation is ongoing as current drug treatments fail to provide fully satisfactory results. In recent years, probiotics have attracted much attention because of their demonstrated therapeutic efficacy and fewer side effects than pharmaceutical products. Many studies attempted to answer the question of how probiotics can alleviate constipation. It has been shown that different probiotic strains can alleviate constipation by different mechanisms. The mechanisms on probiotics in relieving constipation were associated with various aspects, including regulation of the gut microbiota composition, the level of short-chain fatty acids, aquaporin expression levels, neurotransmitters and hormone levels, inflammation, the intestinal environmental metabolic status, neurotrophic factor levels and the body's antioxidant levels. This paper summarizes the perception of the mechanisms on probiotics in relieving constipation and provides some suggestions on new research directions.

How probiotics, prebiotics, synbiotics, and postbiotics prevent dental caries: an oral microbiota perspective.

Dental caries, a highly prevalent oral disease, impacts a significant portion of the global population. Conventional approaches that indiscriminately eradicate microbes disrupt the natural equilibrium of the oral microbiota. In contrast, biointervention strategies aim to restore this balance by introducing beneficial microorganisms or inhibiting cariogenic ones. Over the past three decades, microbial preparations have garnered considerable attention in dental research for the prevention and treatment of dental caries. However, unlike related pathologies in the gastrointestinal, vaginal, and respiratory tracts, dental caries occurs on hard tissues such as tooth enamel and is closely associated with localized acid overproduction facilitated by cariogenic biofilms. Therefore, it is insufficient to rely solely on previous mechanisms to delineate the role of microbial preparations in the oral cavity. A more comprehensive perspective should involve considering the concepts of cariogenic biofilms. This review elucidates the latest research progress, mechanisms of action, challenges, and future research directions regarding probiotics, prebiotics, synbiotics, and postbiotics for the prevention and treatment of dental caries, taking into account the unique pathogenic mechanisms of dental caries. With an enhanced understanding of oral microbiota, personalized microbial therapy will emerge as a critical future research trend.

Exopolysaccharides produced by Antrodia cinnamomea using microparticle-enhanced cultivation: Optimization, primary structure and antibacterial property.

Microparticle-enhanced cultivation was used to enhance the production of exopolysaccharides (EPSs) from Antrodia cinnamomea. The structure and antibacterial activity of two EPSs produced by A. cinnamomea treated with Al2O3 [EPS-Al (crude) and EPS-Al-p (purified)] and without Al2O3 [EPS-C (crude) and EPS-C-p (purified)] were compared. It was observed that the addition of 4 g/L Al2O3 at 0 h resulted in the highest EPS yield of 1.46 g/L, possible attributed to the enhanced permeability of the cell membrane. The structural analysis revealed that EPS-C-p and EPS-Al-p had different structures. EPS-C-p was hyperbranched and spherical with a Mw of 10.8 kDa, while EPS-Al-p was irregular and linear with a Mw of 12.5 kDa. The proportion of Man in EPS-Al-p decreased, while those of Gal and Glc increased when compared to EPS-C-p. The total molar ratios of 6-Glcp and 4-Glcp in EPS-Al-p are 1.45 times that of EPS-C-p. Moreover, EPSs could alter bacterial cell morphology, causing intracellular substance leakage and growth inhibition, with EPS-Al having a stronger antibacterial activity than EPS-C. In conclusion, A. cinnamomea treated with Al2O3 could produce more EPSs, changing monosaccharide composition and glycosidic linkage profile, which could exert stronger antibacterial activity than that produced by untreated A. cinnamomea.

Lesson learned from COVID-19 pandemic for the future of food industry.

With WHO announcing COVID-19 no longer as a public health emergency of international concern (PHEIC) on May 5, 2023, coupled with the fact that the majority of the countries of the world have dropped strict city lockdown or border closure, this perhaps signals the end of the COVID-19 crisis caused by the SARS-CoV-2 virus. However, the COVID-19 pandemic has resulted in far-reaching effects affecting nearly every aspect of our lives and society. Notably, the food industry including agriculture, food manufacturers, food logistics, distributors and retailers have all felt the profound impact and had experienced significant stress during the pandemic. Therefore, it is essential to retrospect the lessons that can be learned from this pandemic for the food industry. This short review aims to address the food safety issues related to the COVID-19 pandemic by focusing on its foodborne transmission potential, innovations of virus detection strategies suitable for food industry; development of phathogenicaidal methods and devices to inactivate SARS-CoV-2 virus (particularly in industrial scale); and the set-up of related food regulations and guidelines as preventive and control measures for preventing the spread of SARS-CoV-2 virus through the food supply chain during the pandemic. This article may provide useful references for the food industry to minimize the food safety impact of COVID-19 (as well as other respiratory virus) and allows them to better prepare for similar future challenges.

Advances in multifunctional biomass-derived nanocomposite films for active and sustainable food packaging.

Innovative food packaging techniques provide extrinsic systems for ensuring the quality and safety of food products. Recent research has focused on the development of multifunctional nanocomposites towards emerging active and sustainable food packaging (ASFP) systems. Specifically, diverse biomass-derived nanocomposite films (BNFs) are engineered via incorporating functional nanomaterials into the naturally-occurring biopolymers (e.g., polysaccharides and proteins). Such BNFs lead to minimum environmental risks compared to petroleum-derived materials, while exhibit improved physicochemical properties and functionalities, demonstrating great potential for ASFP. This review provides a summary of state-of-art BNFs based on their composition and application. We also highlight the advantages of BNFs for agricultural products. Particularly, the interactions between the biomass matrix and the nanomaterials are discussed to provide insightful rationales for designing high-performance BNFs. We envision that BNFs will not only be emerged as the dominant food packaging materials, but also contribute to the international trade and addressing the global food crisis.

Cancer immunotherapeutic effect of carboxymethylated ß-d-glucan coupled with iron oxide nanoparticles via reprogramming tumor-associated macrophages.

The cancer immunotherapeutic effect of a carboxymethylated ß-d-glucan (CMPTR)/iron oxide nanoparticles (IONPs) system (CMPTR/IONPs) were investigated by using cell culture of bone marrow-derived macrophages (BMDMs) and B16F10 melanoma skin cancer-bearing mouse model. When compared with that of control group, CMPTR/IONPs-treated M2-like BMDMs exhibited upregulated M1 biomarkers expression, significantly inhibited the migration of B16F10 cancer cells (p < 0.05), and had the highest apoptotic percentage of B16F10 cancer cells (80.39 ± 8.73 %) in co-culture system. Intratumoral administration of CMPTR/IONPs significantly (p < 0.05) suppressed tumor growth (46.58 % based on tumor weight) in mice and enhanced the M1/M2 ratio from 0.40 ± 0.09 (control group) to 6.64 ± 1.61 in tumor associated macrophages (TAMs) which was higher than that of in CMPTR (1.27 ± 0.38), IONPs (1.38 ± 0.17). CMPTR/IONPs treatment also promoted apoptosis in cancer cells and increased the infiltration of CD4 and CD8 T-lymphocytes in tumor tissues. These results could be due to the combined effects of CMPTR and IONPs in the CMPTR/IONPs system, possibly mediated by the activation of NF-κB and IRF5 pathways for inducing M1 macrophages polarization and had potential cancer immunotherapeutic applications.

A Tumor-Targeting Dual-Stimuli-Activatable Photodynamic Molecular Beacon for Precise Photodynamic Therapy.

A multifunctional photodynamic molecular beacon (PMB) has been designed and synthesized which contains an epidermal growth factor receptor (EGFR)-targeting cyclic peptide and a trimeric phthalocyanine skeleton in which the three zinc(II) phthalocyanine units are each substituted with a glutathione (GSH)-responsive 2,4-dinitrobenzenesulfonate (DNBS) quencher and are linked via two cathepsin B-cleavable GFLG peptide chains. This tailor-made conjugate is fully quenched in the native form due to the photoinduced electron transfer effect of the DNBS moieties and the self-quenching of the phthalocyanine units. It can target the EGFR overexpressed in cancer cells, and after receptor-mediated endocytosis, it can be activated selectively by the co-existence of intracellular GSH and cathepsin B, both of which are also overproduced in cancer cells, in terms of fluorescence emission and singlet oxygen generation. The cell-selective behavior of this PMB has been demonstrated using a range of cancer cells with different expression levels of EGFR, while the stimuli-responsive properties have been studied both in vitro and in various aqueous media. The overall results show that this advanced PMB, which exhibits several levels of control of the tumor specificity, is a promising photosensitizer for precise antitumoral photodynamic therapy.

Mushroom Carboxymethylated ß-d-Glucan Functions as a Macrophage-Targeting Carrier for Iron Oxide Nanoparticles and an Inducer of Proinflammatory Macrophage Polarization for Immunotherapy.

ß-d-glucans have the potential of serving as both macrophage-targeted carriers and immune stimulators via inducing trained immunity in macrophages. In this study, a carboxymethylated ß-glucan from mushroom sclerotium of Pleurotus tuber-regium (CMPTR) was combined with iron oxide nanoparticles (IONPs) to form nanocomplexes (CMPTR/IONPs) with particle size around 193 ± 7 nm, which could exert a concerted effect on inducing proinflammatory M1 phenotype macrophages for immunotherapy. This nanocomplex exhibited good stability and low cytotoxicity (over 80% cellular viability of RAW 264.7 and THP-1) and higher cellular uptake by murine macrophages compared with B16F10 cells (p < 0.05). CMPTR/IONPs could convert M2-like bone marrow-derived macrophages into M1 phenotypes with upregulated expression of pro-inflammatory cytokines (IL12 and TNF-α, p < 0.05) and reduced immune-suppressive cytokines (IL10 and TGF-ß, p < 0.05). Such polarization was mediated by the combined signaling regulatory factors, including IONP-stimulated IRF5 and CMPTR-triggered TLRs-NF-κB pathways (p < 0.05). Accordingly, CMPTR could have a dual function as a macrophage-targeting carrier for IONPs and an immunostimulant to induce inflammatory M1 macrophage polarization for immunotherapy.

Biogenetic nanocarriers with enhanced pH stability formed by zein and selectively depolymerized mushroom hyperbranched ß-glucans.

Hyperbranched polysaccharide from Pleurotus tuber-regium (PTR-HBPS) is a ß-glucan with high degree of branching (DB, 0.69) and a molecular weight (Mw) of 31.2 × 105 g/mol with mixed ß-1, 4/ß-1, 4, 6/ß-1, 6 glucosidic linkages. PTR-HBPS was depolymerized by cellulase and ß-glucosidase under optimized conditions to form PC (PTR-HBPS depolymerized by cellulase) and PG (PTR-HBPS depolymerized by ß-glucosidase) fractions with a minimum Mw of 2.74 × 105 and 3.98 × 105 g/mol, respectively. PC fractions had no significant changes for its primary structure in terms of glycosidic linkages, DB, and triple helical structure, while the DB of PG fractions was reduced to 0.63 with the loss of triple helical structure. Nanoparticles fabricated by PC fractions with zein showed better stability under different pH conditions. Enzymatic depolymerized low Mw ß-glucan derived from PTR-HBPS with similar structural characteristics as the native one has potential as nanocarriers for food bioactive substances.

Stimulating mechanism of corn oil on biomass and polysaccharide production of Pleurotus tuber-regium mycelium.

Hyperbranched polysaccharides (HBPSs) are the main components in cell wall and exopolysaccharide (EPS) of Pleurotus tuber-regium. To enhance the yield of these macromolecules, corn oil at 4% addition exhibited the best effect for production of mycelial biomass at 20.49 g/L and EPS at 0.59 g/L, which was 2.56 folds and 1.90 folds of the control, respectively. The treated hyphae were much thicker with smooth surface, while its cell wall content (43.81 ± 0.02%) was 1.96 times of the control (22.34 ± 0.01%). Moreover, a large number of lipid droplets could be visualized under the view of confocal laser scanning microscopy (CLSM). RNA-seq analysis revealed that corn oil could enter the cells and result in the up-regulation of genes on cell morphology and membrane permeability, as well as the down-regulation on expression level of polysaccharide hydrolase and genes involved in the MAPK pathway, all of which probably contribute to the increase of polysaccharides production.

Beta-d-glucan-based drug delivery system and its potential application in targeting tumor associated macrophages.

Use of polysaccharides as carriers in drug delivery system is a hot topic, especially those with specific recognition of immune cells, enabling them to be applied in targeting delivery system. ß-d-glucans are naturally occurring non-digestible polysaccharides with immunomodulatory activities that have attracted increasing attention to serve as therapeutic agents or immune-adjuvants. Being able to be specifically recognized by immune cells like macrophages, ß-d-glucans can be developed as promising carriers for targeting delivery with stability, biocompatibility and specificity when applied in immunotherapy. Targeting tumor associated macrophages (TAMs) is an emerging strategy for cancer immunotherapy since it exerts anti-cancer effects based on modulating body immunity in tumor microenvironment (TME). This new strategy does not require high concentration of drugs to kill cancer cells directly and lessen tumor recurrence by creating unique immune memory for malignant cells. In this review, construction strategies of polysaccharide-based drug delivery system of three types of ß-d-glucan including non-yeast and yeast ß-d-glucans as well as hyper-branched ß-d-glucan are discussed with reference to their branching characteristics and conformation. The applications of these ß-d-glucans as nano-carrier for drug delivery targeting TAMs are also discussed.

Research on a Specialty Mushroom (Pleurotus tuber-regium) as a Functional Food: Chemical Composition and Biological Activities.

Pleurotus tuber-regium (PTR) is an edible specialty mushroom that has attracted growing interest recently because of its sensory attributes, high nutritional values, and important medicinal properties. PTR is rich in bioactive polysaccharides, proteins with essential amino acids, essential fatty acids, dietary fiber, minerals, and vitamins. Current studies have shown that the nutrients and bioactive ingredients of PTR contribute to their antitumor, antihypercholesterolemic, antihypertensive, antiobesity, hepatic-protective, antimicrobial, antioxidant, and prebiotic activities, indicating that PTR is a promising functional food and nutraceutical. In this review, the chemical constituents and physiological functions of PTR are summarized, which provide the scientific basis to support the further research and development of its application in the food and pharmaceutical industries.

pH-sensitive PEG-coated hyper-branched ß-d-glucan derivative as carrier for CpG oligodeoxynucleotide delivery.

ß-d-glucan is a natural non-digestible polysaccharide that can be selectively recognized by recognition receptors such as Dectin-1 receptors, resulting in an emerging interest on exploring its capacity for carrying biological information to desired organs or cells. CpG oligodeoxynucleotide (ODN) has the potentiality to initiate an immune-stimulatory cascade via activating B cells inducing proinflammatory cytokines, which is conducive to immunotherapy and nucleic acid vaccine. Herein, we developed a pH-sensitive delivery system loading with CpG ODN by introducing poly-ethylenimine (PEI) to a hyperbranched ß-d-glucan (HBB) and coating with poly-ethylene glycol (PEG) shell via acidic liable Schiff bond. This delivery system exhibited a favorable biocompatibility and facilitated the cellular uptake of CpG ODN at pH 6.8 with the possibility of having higher accumulation in acidic cancer microenvironment. Furthermore, this carrier together with class B CpG ODN could enhance the secretion of cytokines including interleukin-6 and interferon-α as well as capable of interferon-α induction.

Anti-Inflammatory Activity of the Wild Mushroom, Echinodontium tinctorium, in RAW264.7 Macrophage Cells and Mouse Microcirculation.

The aim of this study was to investigate the anti-inflammatory activity of a previously un-studied wild mushroom, Echinodontium tinctorium, collected from the forests of north-central British Columbia. The lipopolysaccharide (LPS)-induced RAW264.7 macrophage model was used to study the in vitro anti-inflammatory activity. The crude alkaline extract demonstrated potent anti-inflammatory activity, and was further purified using a "bio-activity-guided-purification" approach. The size-exclusion and ion-exchange chromatography yielded a water-soluble anti-inflammatory polysaccharide (AIPetinc). AIPetinc has an average molecular weight of 5 kDa, and is a heteroglucan composed of mainly glucose (88.6%) with a small amount of galactose (4.0%), mannose (4.4%), fucose (0.7%), and xylose (2.3%). In in vivo settings, AIPetinc restored the histamine-induced inflammatory event in mouse gluteus maximus muscle, thus confirming its anti-inflammatory activity in an animal model. This study constitutes the first report on the bioactivity of Echinodontium tinctorium, and highlights the potential medicinal benefits of fungi from the wild forests of northern British Columbia. Furthermore, it also reiterates the need to explore natural resources for alternative treatment to modern world diseases.

Immunomodulatory Effect of Structurally Characterized Mushroom Sclerotial Polysaccharides Isolated from Polyporus rhinocerus on Bone Marrow Dendritic Cells.

This study evaluated the immunomodulatory effects of two high-molecular-weight and structurally different mushroom polysaccharides, an alkali-soluble polysaccharide (mPRSon) and a water-soluble polysaccharide-protein complex (PRW), isolated previously from the sclerotia of Pleurotus rhinocerus, on the maturation of murine bone-marrow-derived dendritic cells (BMDCs). The effects of mPRSon and PRW on the expression of morphological change, surface molecules, phagocytic activity, and cytokine release in BMDCs were determined by flow cytometry and a mouse cytokine array. The results showed that both mPRSon and PRW could induce phenotypic and functional maturation of BMDCs. At the same time, mPRSon upregulated the expression of membrane phenotypic marker CD86 and PRW markedly upregulated CD40, CD80, and CD86. In addition, mPRSon could bind to the dectin-1 receptor and stimulate the release of MIP-1α, MIP-2, and IL-2, while PRW could bind to complement receptor 3 and toll-like receptor 2 with an upregulation of the expression of IL-2, IL-6, MIP-1α, MIP-2, RANTES, IL-12p40p70, IL-12p70, TIMP-1, IFN-γ, KC, MCP-1, and GCSF. The study provides additional information on how structural differences in sclerotial polysaccharides influence their immunomodulatory activities on BMDCs involving different PAMP receptors. It is anticipated that more understanding of the interactions between the sclerotial polysaccharides and their receptors in immune cells can facilitate their future application for cancer immunotherapy.

Structure, bioactivity and applications of natural hyperbranched polysaccharides.

In recent years, hyperbranched polymers, especially the natural hyperbranched polysaccharides (HBPSs), are receiving much attention due to their diverse biological activities and applications. With high degree of branching (DB), HBPSs mainly exist in the form of either a comb-brush shape, dendrimer-like particulate, or globular particle. HBPSs also possess some unique properties, such as high density, large spatial cavities, and numerous terminal functional groups, which distinguish them from other polymers. As a natural biopolymer, HBPS has excellent bioavailability, biocompatibility, and biodegradability, which have versatile applications in the fields of food, medicine, cosmetic, and nanomaterials. In this review, the source and structure of HBPSs from plant, animal, microbial and fungal origins as well as their biological functions and applications are covered, with the aim of further advancing the research of their structure and bioactivity.

Structure and Immunomodulatory Activity of Microparticulate Mushroom Sclerotial ß-Glucan Prepared from Polyporus rhinocerus.

In this study, an immunologically active novel microparticulate mushroom ß-glucan (PRA-1p) was prepared using an alkali-soluble glucan PRA-1 by an emulsification and cross-linking method. PRA-1 was a hyperbranched (1→3),(1→6)-ß-d-glucan with a degree of branching of 0.89, isolated from the sclerotia of Polyporus rhinocerus. PRA-1 had a rod-like conformation, while PRA-1p exhibited a monodisperse and homogeneous spherical conformation with a diameter ranging from 0.3 to 2.0 µm in water. PRA-1p significantly induced nitric oxide and reactive oxygen species production as well as morphological changes of murine macrophages (RAW 264.7 cells) and upregulated their phagocytic activity. Furthermore, PRA-1p treatment markedly enhanced the secretion of cytokines, including cutaneous T cell-attracting chemokine 27, granulocyte-colony-stimulating factor, monocyte chemoattractant protein 1, macrophage inflammatory protein 1α, macrophage inflammatory protein 2, regulated on activation, normal T cell expressed and secreted, soluble tumor necrosis factor receptor 1, and tissue inhibitors of metalloproteinases. Activation of RAW 264.7 cells triggered by PRA-1p was associated with activation of inducible nitric oxide synthase, nuclear factor κB, extracellular signal-regulated kinase, and protein kinase B. This work suggests that novel PRA-1p derived from the mushroom sclerotia of P. rhinocerus has potential application as an immunostimulatory agent.

Synbiotic-driven improvement of metabolic disturbances is associated with changes in the gut microbiome in diet-induced obese mice.

OBJECTIVE: The gut microbiota is an important influencing factor of metabolic health. Although dietary interventions with probiotics, prebiotics, and synbiotics can be effective means to regulate obesity and associated comorbidities, the underlying shifts in gut microbial communities, especially at the functional level, have not been characterized in great details. In this study, we sought to investigate the effects of synbiotics on the regulation of gut microbiota and the alleviation of high-fat diet (HFD)-induced metabolic disorders in mice. METHODS: Specific pathogen-free (SPF) male C57BL/6J mice were fed diets with either 10% (normal diet, ND) or 60% (high-fat diet, HFD) of total calories from fat (lard). Dietary interventions in the HFD-fed mice included (i) probiotic (Bifidobacterium animalis subsp. lactis and Lactobacillus paracasei subsp. paracasei DSM 46331), (ii) prebiotic (oat ß-glucan), and (iii) synbiotic (a mixture of i and ii) treatments for 12 weeks. Besides detailed characterization of host metabolic parameters, a multi-omics approach was used to systematically profile the microbial signatures at both the phylogenetic and functional levels using 16S rRNA gene sequencing, metaproteomics and targeted metabolomics analysis. RESULTS: The synbiotic intervention significantly reduced body weight gain and alleviated features of metabolic complications. At the phylogenetic level, the synbiotic treatment significantly reversed HFD-induced changes in microbial populations, both in terms of richness and the relative abundance of specific taxa. Potentially important species such as Faecalibaculum rodentium and Alistipes putredinis that might mediate the beneficial effects of the synbiotic were identified. At the functional level, short-chain fatty acid and bile acid profiles revealed that all dietary interventions significantly restored cecal levels of acetate, propionate, and butyrate, while the synbiotic treatment reduced the bile acid pools most efficiently. Metaproteomics revealed that the effects of the synbiotic intervention might be mediated through metabolic pathways involved in carbohydrate, amino acid, and energy metabolisms. CONCLUSIONS: Our results suggested that dietary intervention using the novel synbiotic can alleviate HFD-induced weight gain and restore gut microbial ecosystem homeostasis phylogenetically and functionally.

Production of bioactive metabolites by submerged fermentation of the medicinal mushroom Antrodia cinnamomea: recent advances and future development.

Edible and medicinal mushrooms have usually been considered as a sustainable source of unique bioactive metabolites, which are valued as promising provisions for human health. Antrodia cinnamomea is a unique edible and medicinal fungus widespread in Taiwan, which has attracted much attention in recent years for its high value in both scientific research and commercial applications owing to its potent therapeutic effects, especially for its hepatic protection and anticancer activity. Due to the scarcity of the fruiting bodies, the cultivation of A. cinnamomea by submerged fermentation appears to be a promising substitute which possesses some unique advantages, such as short culture time period and its high feasibility for scale-up production. However, the amount of fungal bioactive metabolites derived from the cultured mycelia of A. cinnamomea grown by submerged fermentation is much less than those obtained from the wild fruiting bodies. Hence, there is an urgent need to bridge such a discrepancy on bioactive metabolites between the wild fruiting bodies and the cultured mycelia. The objective of this article is to review recent advances and the future development of the mycelial submerged fermentation of A. cinnamomea in terms of enhancement for the production of fungal bioactive components by the optimization of culture conditions and the regulation of fungal metabolism. This review provides valuable information for further biotechnological applications of A. cinnamomea as well as other mushrooms being the source of bioactive ingredients by submerged fermentation.