Glutamine-derived peptides: Current progress and future directions.

Glutamine, the most abundant amino acid in the body, plays a critical role in preserving immune function, nitrogen balance, intestinal integrity, and resistance to infection. However, its limited solubility and instability present challenges for its use a functional nutrient. Consequently, there is a preference for utilizing glutamine-derived peptides as an alternative to achieve enhanced functionality. This article aims to review the applications of glutamine monomers in clinical, sports, and enteral nutrition. It compares the functional effectiveness of monomers and glutamine-derived peptides and provides a comprehensive assessment of glutamine-derived peptides in terms of their classification, preparation, mechanism of absorption, and biological activity. Furthermore, this study explores the potential integration of artificial intelligence (AI)-based peptidomics and synthetic biology in the de novo design and large-scale production of these peptides. The findings reveal that glutamine-derived peptides possess significant structure-related bioactivities, with the smaller molecular weight fraction serving as the primary active ingredient. These peptides possess the ability to promote intestinal homeostasis, exert hypotensive and hypoglycemic effects, and display antioxidant properties. However, our understanding of the structure-function relationships of glutamine-derived peptides remains largely exploratory at current stage. The combination of AI based peptidomics and synthetic biology presents an opportunity to explore the untapped resources of glutamine-derived peptides as functional food ingredients. Additionally, the utilization and bioavailability of these peptides can be enhanced through the use of delivery systems in vivo. This review serves as a valuable reference for future investigations of and developments in the discovery, functional validation, and biomanufacturing of glutamine-derived peptides in food science.

L-Alanine promotes anti-infectious properties of Bacillus subtilis S-2 spores via the germination receptor gerAA.

Bacillus species, which have two cell-type forms (vegetative cells and spores), demonstrate a variety of probiotic functions in animal feed additives and human nutrition. We previously found that the probiotic effect of Bacillus subtilis S-2 spores with high germination response to L-alanine was specifically enhanced by the L-alanine pretreatment. The germination response of Bacillus is highly associated with the germination receptors of spores. However, how L-alanine-induced germination of spores exerts anti-infectious effect in epithelial cells remains unclear. In this study, we constructed the mutant strain of B. subtilis S-2 with germination receptor gerAA knockout to further explore the role of spore germination in resisting pathogen infection to cells. The differential probiotic effects of B. subtilis S-2 and S-2ΔgerAA spores pretreated with L-alanine were evaluated in intestinal porcine epithelial cells (IPEC-J2) or Caco2 cells infected with enterotoxigenic Escherichia coli (ETEC) or following IL-1ß stimulation. The results showed that the germination response of the S-2ΔgerAA spores to L-alanine was significantly reduced. Compared with the S-2ΔgerAA spores, the L-alanine-induced germination of B. subtilis S-2 spores significantly increased the activity of anti-adhesion of ETEC to IPEC-J2 cells and reduced the expression of inflammatory factors and cell receptors. L-alanine induction also significantly promoted the expression of autophagy-related proteins in the B. subtilis S-2 spores. These findings demonstrate that the gerAA germination receptor is essential for the probiotic function of Bacillus spores and that L-alanine treatment promotes the anti-infectious properties of the germinated spores in porcine intestinal epithelial IPEC-J2 cells. The result suggests the importance of germination receptor gerAA in helping spore germination and enhancing anti-infectious activity. The findings in the study benefit to screening of potential Bacillus probiotics and increasing probiotic efficacy induced by L-alanine as an adjuvant.

Alginate oligosaccharide structures differentially affect DSS-induced colitis in mice by modulating gut microbiota.

Alginate oligosaccharides (AOS) are divided by their monomer sequences into three types: oligomannuronate (MAOS), oligoguluronate (GAOS), and heterogeneous AOS (HAOS). However, how these AOS structures differentially regulate health and modulate gut microbiota is unclear. We explored the structure-function relationship of AOS both in an in vivo colitis model and an in vitro enterotoxigenic Escherichia coli (ETEC)-challenged cell model. We found that MAOS administration significantly alleviated the symptom of experimental colitis and improved the gut barrier function in vivo and in vivo. Nevertheless, HAOS and GAOS were less effective than MAOS. The abundance and diversity of gut microbiota are obviously increased by MAOS intervention, but not by HAOS or GAOS. Importantly, microbiota from MAOS-dosed mice through FMT decreased the disease index level, alleviated histopathological changes, and improved gut barrier function in the colitis model. Super FMT donors induced by MAOS but not by HAOS or GAOS, seemed to exert potential in colitis bacteriotherapy. These findings may aid in establishing precise pharmaceutical applications based on the targeted production of AOS.

Effects of chitosan oligosaccharides (COS) and FMT from COS-dosed mice on intestinal barrier function and cell apoptosis.

Chitosan oligosaccharides (COS) show the potential to support the intestinal health, but the mechanism and role of COS-derived intestinal microbiota are unknown. We explored the protective effect of direct administration of COS on intestinal barrier function using an in vivo colitis mouse model and an in vitro enterotoxigenic Escherichia coli (ETEC)-challenged IPEC-J2 cell model. COS directly enhanced the intestinal barrier function. COS intervention also promoted the abundance and diversity of intestinal flora. Importantly, FMT intervention with a COS-derived microbiome decreased the disease index level and alleviated histopathological changes, and improved gut barrier function in the colitis model. Both COS and COS-derived microbiota suppressed ETEC-induced cellular apoptosis in IPEC-J2 cells. This study firstly confirms transplantation of COS-modified fecal microbiota can enhance the intestinal barrier function. The mechanism underlying COS benefits is due to a direct intervention by COS supplementation and an indirect improvement of the gut microbiota induced by COS exposure.

Bacillus-derived probiotics: metabolites and mechanisms involved in bacteria-host interactions.

Bacillus probiotics have a sporulation capacity that makes them more suitable for processing and storage and for surviving passage through the gastrointestinal tract. The probiotic functions and regulatory mechanisms of different Bacillus have been exploited in many reports, but little is known about how various Bacillus probiotics perform different functions. This knowledge gap results in a lack of specificity in the selection and application of Bacillus. The probiotic properties are strain-specific and cell-type-specific, and are related to the germination potential and to the diversity of metabolites produced following intestinal germination, as this causes the variation in probiotic function and mechanisms. In this review, we discuss the Bacillus metabolites produced during germination and sporulation in the GI tract, as well as possible processes affecting intestinal homeostasis. We conclude that the oxygen-capturing capability and the production of antimicrobials, exoenzymes, competence and sporulation factors (CSF), exopolysaccharides, lactic acid, and cell components are specifically associated with the functional mechanisms of probiotic Bacillus. The aim of this review is to guide the screening of potential Bacillus strains for probiotics and their application in nutrition research. The information provided will also promote further research on Bacillus-derived functional metabolites in human nutrition.

Alginate oligosaccharides: The structure-function relationships and the directional preparation for application.

Alginate oligosaccharides (AOS) are degradation products of alginate extracted from brown algae. With low molecular weight, high water solubility, and good biological activity, AOS present anti-inflammatory, antimicrobial, antioxidant, and antitumor properties. They also exert growth-promoting effects in animals and plants. Three types of AOS, mannuronate oligosaccharides (MAOS), guluronate oligosaccharides (GAOS), and heterozygous mannuronate and guluronate oligosaccharides (HAOS), can be produced from alginate by enzymatic hydrolysis. Thus far, most studies on the applications and biological activities of AOS have been based mainly on a hybrid form of HAOS. To improve the directional production of AOS for practical applications, systematic studies on the structures and related biological activities of AOS are needed. This review provides a summary of current understanding of structure-function relationships and advances in the production of AOS. The current challenges and opportunities in the application of AOS is suggested to guide the precise application of AOS in practice.