Postbióticos: un nuevo miembro en la familia de los bióticos / Postbiotics: A new member in the biotics family

Los postbióticos fueron definidos en 2021 por la Asociación Científica Internacional de Probióticos y Prebióticos (ISAPP) como "una preparación de microorganismos inanimados y/o sus componentes celulares capaces de conferir un efecto benéfico al hospedador". El campo de los postbióticos es un área nueva dentro de la familia de los bióticos; se han desarrollado ya numerosos productos con aplicaciones clínicas, como la estimulación inmunológica, el manejo de diarreas en niños y adultos, el abordaje del intestino irritable, además de tres fórmulas infantiles. En particular, las fórmulas infantiles con postbióticos obtenidos a partir de la fermentación de la leche con Bifidobacterium breve C50 y Streptococcus thermophilus O65, y sus metabolitos, incluido el oligosacárido 3'-GL, han demostrado seguridad y contribución al desarrollo de la microbiota intestinal y el sistema inmune asociado al intestino. Estas modificaciones contribuyen a la prevención y el manejo de los trastornos funcionales digestivos del lactante.

Postbiotics were defined in 2021 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) as a "preparation of inanimate microorganisms and/or their cellular components that confers a health benefit to the host." The field of postbiotics is a new area within the biotics family; numerous products have already been developed for clinical applications, such as immune stimulation, the management of diarrhea in children and adults, the management of irritable bowel syndrome, and 3 infant formulas. In particular, infant formulas with postbiotics obtained from milk fermented with Bifidobacterium breve C50 and Streptococcus thermophilus O65 ­and their metabolites­, including the oligosaccharide 3'-GL, have demonstrated to be safe and to contribute to the development of the gut microbiota and the gutassociated immune system. These modifications help to prevent and manage functional gastrointestinal disorders in infants.

Appraisal of postbiotics in cancer therapy.

Cancer remains a multifactorial disease with an increased mortality rate around the world for the past several decades. Despite advancements in treatment strategies, lower survival rates, drug-associated side effects, and drug resistance create a need for novel anticancer agents. Ample evidence shows that imbalances in the gut microbiota are associated with the formation of cancer and its progression. Altering the gut microbiota via probiotics and their metabolites has gained attention among the research community as an alternative therapy to treat cancer. Probiotics exhibit health benefits as well as modulate the immunological and cellular responses in the host. Apart from probiotics, their secreted products like bacteriocins, exopolysaccharides, short-chain fatty acids, conjugated linoleic acid, peptidoglycan, and other metabolites are found to possess anticancer activity. The beneficiary role of these postbiotic compounds is widely studied for characterizing their mechanism and mode of action that reduces cancer growth. The present review mainly focuses on the postbiotic components that are employed against cancer with their reported mechanism of action. It also describes recent research works carried out so far with specific strain and anticancer activity of derived compounds both in vitro and in vivo, validating that the probiotic approach would pave an alternative way to reduce the burden of cancer.

A Comprehensive Overview of Postbiotics with a Special Focus on Discovery Techniques and Clinical Applications.

The increasing interest in postbiotics, a term gaining recognition alongside probiotics and prebiotics, aligns with a growing number of clinical trials demonstrating positive outcomes for specific conditions. Postbiotics present several advantages, including safety, extended shelf life, ease of administration, absence of risk, and patentability, making them more appealing than probiotics alone. This review covers various aspects, starting with an introduction, terminology, classification of postbiotics, and brief mechanisms of action. It emphasizes microbial metabolomics as the initial step in discovering novel postbiotics. Commonly employed techniques such as NMR, GC-MS, and LC-MS are briefly outlined, along with their application principles and limitations in microbial metabolomics. The review also examines existing research where these techniques were used to identify, isolate, and characterize postbiotics derived from different microbial sources. The discovery section concludes by highlighting challenges and future directions to enhance postbiotic discovery. In the second half of the review, we delve deeper into numerous published postbiotic clinical trials to date. We provide brief overviews of system-specific trial applications, their objectives, the postbiotics tested, and their outcomes. The review concludes by highlighting ongoing applications of postbiotics in extended clinical trials, offering a comprehensive overview of the current landscape in this evolving field.

Changes in Digestive Health, Satiety and Overall Well-Being after 14 Days of a Multi-Functional GI Primer Supplement.

A recent review proposed a role for multi-functional food or supplement products in priming the gut to support both digestive and systemic health. Accordingly, we designed and eva-luated the effect of a multi-functional gastrointestinal (GI) primer supplement on participant-reported measures for digestive health, quality-of-life (e.g., energy/vitality and general health), and reasons for satiation (e.g., attitudes towards food and eating). In this single-arm clinical trial, 68 participants with mild digestive symptoms consumed the GI primer supplement daily for 14 days. Digestive symptoms were evaluated daily from baseline (Day 0) through Day 14. At baseline and Day 14, participants reported their stool consistency, reasons for satiation, and quality-of-life measures using validated questionnaires. At Day 14, participants reported significant improvements in all (13/13) digestive symptom parameters (p-values < 0.05) and an increase in % of stools with normal consistencies. There were significant improvements (p-values < 0.05) in energy/vitality and general health, and in specific attitudes towards food and eating (e.g., physical satisfaction, planned amount, decreased eating priority, decreased food appeal, and self-consciousness). Results suggest the GI primer supplement promotes digestive health, improves quality of life, and impacts attitudes towards food/eating. This study provides preliminary support for the gut priming hypothesis through which multi-functional digestive products may improve GI health.

Aggregation and adhesion ability of various probiotic strains and Candida species: An in vitro study.

Background/purpose: The ability of probiotics to inhibit Candida adhesion is a crucial characteristic that prevents Candida colonization and infection progression. This study aimed to explore aggregation, adhesion, and cell surface characterization of probiotic and Candida strains and to evaluate the effect of probiotics and their cell-free supernatants (CFSs) as postbiotics on Candida adhesion to human oral keratinocytes. Materials and methods: Eight probiotic strains and five reference Candida strains were tested for autoaggregation, coaggregation, adhesin on human oral keratinocytes (H357), and cell surface properties. The anti-Candida adhesion activities of probiotic strains and CFSs were investigated. Results: The results showed that most probiotics exhibited high adhesion to H357 cells, specifically oral probiotic Lacticaseibacillus rhamnosus SD4, Limosilactobacillus fermentum SD7, and L. rhamnosus SD11, and adhesion ability of probiotic strains was strongly related to their autoaggregation, cell surface charges, and hydrophobicity. Candida strains also revealed a high level of adhesion to H357 cells. Candida albicans and C andida glabrata showed significantly higher adhesion abilities than others. After a combination of Candida with probiotics or their CFSs, Candida adhesion was significantly reduced. The anti-Candida adhesion property of probiotics was strongly related to their autoaggregation, coaggregation, and adhesion abilities. Conclusion: This study demonstrated that oral probiotic strains may be useful probiotics for preventing and treating oral candidiasis due to their high ability of aggregation, adhesion, and anti-Candida adhesion to H357 cells.

Candidate-Probiotic Lactobacilli and Their Postbiotics as Health-Benefit Promoters.

Lactobacillus species are widely recognized for their probiotic potential, focusing on their mechanisms of health benefits and protection. Here we conducted an in vitro investigation of the probiotic potential with a role in microbiome homeostasis of four strains: Lactiplantibacillus plantarum L6 and F53, Ligilactobacillus salivarius 1, and Lactobacillus helveticus 611. A broad spectrum of antibacterial and antifungal activity was determined. The strain-specific inhibition of Staphylococcus aureus, Streptococcus mutans, Escherichia coli, Pseudomonas aeruginosa, and saprophytic/toxigenic fungi makes them promising as protective cultures. DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid) measurements showed that tested samples had strain-specific capacity for scavenging of radicals. The molecular base for the antioxidant potential of two lyophilized forms of active strains was investigated by electron paramagnetic resonance spectroscopy. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, with fractions of the most active postbiotics obtained by SEC-FPLC (fast protein liquid chromatography) analysis, showed a wide variety of effects on the growth of a K562 myeloid leukemia cell line. The IC50 (half-maximal inhibitory concentration) of L. salivarius 1 was determined to be 46.15 mg/mL. The proven in vitro functionality of the selected lactobacilli make them suitable for development of target probiotics with specific beneficial effects expected in vivo. Further investigations on produced postbiotics and safety have to be completed before they can be considered as scientifically proven probiotic strains.

Evaluating the antibacterial, antibiofilm, and anti-toxigenic effects of postbiotics from lactic acid bacteria on Clostridium difficile.

Background and Objectives: The most common cause of healthcare-associated diarrhea is Clostridium difficile infection (CDI), which causes severe and recurring symptoms. The increase of antibiotic-resistant C. difficile requires alternate treatments. Postbiotics, metabolites produced by probiotics, fight CDI owing to their antibacterial capabilities. This study aims to evaluate the antibacterial, antibiofilm, and anti-toxigenic potential of postbiotics in combating CDI. Materials and Methods: GC-MS evaluated postbiotics from Bifidobacterium bifidum and Lactobacillus plantarum. Disk diffusion and broth microdilution determined C. difficile antibacterial inhibition zones and MICs. Microtiter plates assessed antibiofilm activity. MTT assay evaluated postbiotics anti-viability on HEK293. ELISA testing postbiotic detoxification of toxins A and B. Postbiotics were examined for tcdA and tcdB genes expression using real-time PCR. Results: The most identified B. bifidum and L. plantarum postbiotic compounds were glycolic acid (7.2%) and butyric acid (13.57%). B. bifidum and L. plantarum displayed 13 and 10 mm inhibition zones and 2.5 and 5 mg/ml MICs against C. difficile. B. bifidum reduced biofilm at 1.25 mg/ml by 49% and L. plantarum by 31%. MTT assay showed both postbiotics had little influence on cell viability, which was over 80%. The detoxification power of postbiotics revealed that B. bifidum decreased toxin A and B production more effectively than L. plantarum, and also their related tcdA and tcdB genes expression reduction were statistically significant (p < 0.05). Conclusion: Postbiotics' ability to inhibit bacterial growth, biofilm disruption, and toxin reduction makes them a promising adjunctive for CDI treatment and a good solution to pathogens' antibiotic resistance.

Lactobacilli Cell-Free Supernatants Modulate Inflammation and Oxidative Stress in Human Microglia via NRF2-SOD1 Signaling.

Microglia are macrophage cells residing in the brain, where they exert a key role in neuronal protection. Through the gut-brain axis, metabolites produced by gut commensal microbes can influence brain functions, including microglial activity. The nuclear factor erythroid 2-related factor 2 (NRF2) is a key regulator of the oxidative stress response in microglia, controlling the expression of cytoprotective genes. Lactobacilli-derived cell-free supernatants (CFSs) are postbiotics that have shown antioxidant and immunomodulatory effects in several in vitro and in vivo studies. This study aimed to explore the effects of lactobacilli CFSs on modulating microglial responses against oxidative stress and inflammation. HMC3 microglia were exposed to lipopolysaccaride (LPS), as an inflammatory trigger, before and after administration of CFSs from three human gut probiotic species. The NRF2 nuclear protein activation and the expression of NRF2-controlled antioxidant genes were investigated by immunoassay and quantitative RT-PCR, respectively. Furthermore, the level of pro- and anti-inflammatory cytokines was evaluated by immunoassay. All CFSs induced a significant increase of NRF2 nuclear activity in basal conditions and upon inflammation. The transcription of antioxidant genes, namely heme oxygenase 1, superoxide dismutase (SOD), glutathione-S transferase, glutathione peroxidase, and catalase also increased, especially after inflammatory stimulus. Besides, higher SOD1 activity was detected relative to inflamed microglia. In addition, CFSs pre-treatment of microglia attenuated pro-inflammatory TNF-α levels while increasing anti-inflammatory IL-10 levels. These findings confirmed that gut microorganisms' metabolites can play a relevant role in adjuvating the microglia cellular response against neuroinflammation and oxidative stress, which are known to cause neurodegenerative diseases.

New therapy for metabolic syndrome: Gut microbiome supplementation.

The gut microbiota is important in the development and progression of metabolic illnesses such type 2 diabetes, cardiovascular disease (CVD), and obesity. This diverse community of microorganisms controls a variety of physiological functions, including metabolism, inflammation, and immune response. Understanding these interactions has resulted in novel therapeutic options, including microbiome supplementation. The gut microbiome is extremely susceptible to dietary changes, which can alter its makeup and function, influencing metabolite synthesis that affects host health. Certain metabolites, such as butyrate and propionate, have been proven to protect against metabolic illnesses, whereas trimethylamine has been linked to CVD. Prebiotics, probiotics, synbiotics, and postbiotics are being investigated by researchers as ways to change the gut microbiome and boost metabolic health. Despite advances in therapy and lifestyle adjustments, the prevalence of metabolic syndrome is increasing, emphasizing the need for new medicines.

Closed-loop theranostic microgels for immune microenvironment modulation and microbiota remodeling in ulcerative colitis.

Inflammatory bowel disease (IBD) is characterized by the upregulation of reactive oxygen species (ROS) and dysfunction of gut immune system, and microbiota. The conventional treatments mainly focus on symptom control with medication by overuse of drugs. There is an urgent need to develop a closed-loop strategy that combines in situ monitoring and precise treatment. Herein, we innovatively designed the 'cluster munition structure' theranostic microgels to realize the monitoring and therapy for ulcerative colitis (a subtype of IBD). The superoxide anion specific probe (tetraphenylethylene-coelenterazine, TPC) and ROS-responsive nanogels consisting of postbiotics urolithin A (UA) were loaded into alginate and ion-crosslinked to obtain the theranostic microgels. The theranostic microgels could be delivered to the inflammatory site, where the environment-triggered breakup of the microgels and release of the nanogels were achieved in sequence. The TPC-UA group had optimal results in reducing inflammation, repairing colonic epithelial tissue, and remodeling microbiota, leading to inflammation amelioration and recovery of tight junction between the colonic epithelium, and maintenance of gut microbiota. During the recovery process, the local chemiluminescence intensity, which is proportional to the degree of inflammation, was gradually inhibited. The cluster munition of theranostic microgels displayed promising outcomes in monitoring inflammation and precise therapy, and demonstrated the potential for inflammatory disease management.

Health Benefits and Safety of Postbiotics Derived from Different Probiotic Species.

Nowadays, the usage of probiotics in the food industry has become common. It has been proven that probiotics have many health benefits, such as adjusting the intestinal microbiome, boosting the immune system, and enhancing anti-inflammatory and anti-cancer activities. However, in recent years, some concerns have arisen about the consumption of probiotics, especially in vulnerable populations such as elderly, infants, and people with underlying diseases. As a result, finding a new alternative to probiotics that has the same function as probiotics and is safer has been prioritized. In recent years, postbiotics have been introduced as a great replacement for probiotics. However, the safety of these compounds is not exactly confirmed due to the limited in vivo research. In this review, the definition, classification, activities, limitations, and some advantages of postbiotics over probiotics are discussed. Finally, the limited published data about the safety of postbiotics is summarized.

Postbiotic impact on host metabolism and immunity provides therapeutic potential in metabolic disease.

The gut microbiota influences aspects of metabolic disease, including tissue inflammation, adiposity, blood glucose, insulin, and endocrine control of metabolism. Prebiotics or probiotics are often sought to combat metabolic disease. However, prebiotics lack specificity and can have deleterious bacterial community effects. Probiotics require live bacteria to find a colonization niche sufficient to influence host immunity or metabolism. Postbiotics encompass bacterial-derived components and molecules, which are well-positioned to alter host immunometabolism without relying on colonization efficiency or causing widespread effects on the existing microbiota. Here, we summarize the potential for beneficial and detrimental effects of specific postbiotics related to metabolic disease and the underlying mechanisms of action. Bacterial cell wall components such as lipopolysaccharides, muropeptides, lipoteichoic acids and flagellin have context-dependent effects on host metabolism by engaging specific immune responses. Specific types of postbiotics within broad classes of compounds such as lipopolysaccharides, muropeptides can have opposing effects on endocrine control of host metabolism where certain postbiotics are insulin sensitizers and others promote insulin resistance. Bacterial metabolites such as short chain fatty acids, bile acids, lactate, glycerol, succinate, ethanolamine, and ethanol can be substrates for host metabolism. Postbiotics can fuel host metabolic pathways directly or influence endocrine control of metabolism through immunomodulation or mimicking host-derived hormones. The interaction of postbiotics in the host-microbe relationship should be considered during metabolic inflammation and metabolic disease.

Microbial Extracellular Vesicles in Host-Microbiota Interactions.

Extracellular vesicles have emerged as key players in cellular communication, influencing various physiological processes and pathophysiological progression, including digestion, immune response, and tissue repairs. Recently, a class of EVs derived from microbial communities has gained significant attention due to their pivotal role in intercellular communication and their potential as biomarkers and biotherapeutic agents. Microbial EVs are membrane-bound molecules encapsulating bioactive metabolites that modulate host physiological and pathological processes. This chapter discusses the evolving history of microbiota-produced EVs, including their discovery, characterization, current research status, and their diverse mechanisms of interaction with other microbes and hosts. This review also highlights the importance of EVs in health and disease and discusses recent research that shows promising results for the therapeutic potential of EVs.

Synergistic Antidepressant-like Effects of Biotics and n-3 Polyunsaturated Fatty Acids on Dopaminergic Pathway through the Brain-Gut Axis in Rats Exposed to Chronic Mild Stress.

Probiotics, postbiotics, and n-3 polyunsaturated fatty acids (PUFA) have antidepressant-like effects. However, the underlying mechanisms of the dopaminergic pathway are unclear. The present study investigated the hypothesis that probiotics and postbiotics combined with n-3 PUFA synergistically improve depression by modulating the dopaminergic pathway through the brain-gut axis. Rats were randomly divided into seven groups: non-chronic mild stress (CMS) with n-6 PUFA, and CMS with n-6 PUFA, n-3 PUFA, probiotics, postbiotics, probiotics combined with n-3 PUFA, and postbiotics combined with n-3 PUFA. Probiotics, postbiotics, and n-3 PUFA improved depressive behaviors, decreased blood concentrations of interferon-γ, and interleukin-1ß, and increased the brain and gut concentrations of short chain fatty acids and dopamine. Moreover, probiotics, postbiotics, and n-3 PUFA increased the brain and gut expression of glucocorticoid receptor and tyrosine hydroxylase; brain expression of l-type amino acid transporter 1 and dopamine receptor (DR) D1; and gut expression of DRD2. The expression of phosphorylated protein kinase A/protein kinase A and phosphorylated cAMP response element-binding protein/cAMP response element-binding protein increased in the brain, however, decreased in the gut by the supplementation of probiotics, postbiotics, and n-3 PUFA. There was synergistic effect of probiotics and postbiotics combined with n-3 PUFA on the depressive behaviors and dopaminergic pathway in blood, brain, and gut. Moreover, no significant difference in the dopaminergic pathways between the probiotics and postbiotics was observed. In conclusion, probiotics and postbiotics, combined with n-3 PUFA have synergistic antidepressant-like effects on the dopaminergic pathway through the brain-gut axis in rats exposed to CMS.

Benefits and concerns of probiotics: an overview of the potential genotoxicity of the colibactin-producing Escherichia coli Nissle 1917 strain.

Recently, the mounting integration of probiotics into human health strategies has gathered considerable attention. Although the benefits of probiotics have been widely recognized in patients with gastrointestinal disorders, immune system modulation, and chronic-degenerative diseases, there is a growing need to evaluate their potential risks. In this context, new concerns have arisen regarding the safety of probiotics as some strains may have adverse effects in humans. Among these strains, Escherichia coli Nissle 1917 (EcN) exhibited traits of concern due to a pathogenic locus in its genome that produces potentially genotoxic metabolites. As the use of probiotics for therapeutic purposes is increasing, the effects of potentially harmful probiotics must be carefully evaluated. To this end, in this narrative review article, we reported the findings of the most relevant in vitro and in vivo studies investigating the expanding applications of probiotics and their impact on human well-being addressing concerns arising from the presence of antibiotic resistance and pathogenic elements, with a focus on the polyketide synthase (pks) pathogenic island of EcN. In this context, the literature data here discussed encourages a thorough profiling of probiotics to identify potential harmful elements as done for EcN where potential genotoxic effects of colibactin, a secondary metabolite, were observed. Specifically, while some studies suggest EcN is safe for gastrointestinal health, conflicting findings highlight the need for further research to clarify its safety and optimize its use in therapy. Overall, the data here presented suggest that a comprehensive assessment of the evolving landscape of probiotics is essential to make evidence-based decisions and ensure their correct use in humans.

The interplay between probiotics and host autophagy: mechanisms of action and emerging insights.

Autophagy, a lysosome-dependent protein degradation mechanism, is a highly conserved catabolic process seen in all eukaryotes. This cell protection system, which is present in all tissues and functions at a basic level, can be up- or downregulated in response to various stresses. A disruption in the natural route of the autophagy process is frequently followed by an interruption in the inherent operation of the body's cells and organs. Probiotics are live bacteria that protect the host through various mechanisms. One of the processes through which probiotics exert their beneficial effects on various cells and tissues is autophagy. Autophagy can assist in maintaining host homeostasis by stimulating the immune system and affecting numerous physiological and pathological responses. In this review, we particularly focus on autophagy impairments occurring in several human illnesses and investigate how probiotics affect the autophagy process under various circumstances.Abbreviation: AD: Alzheimer disease; AKT: AKT serine/threonine kinase; AMPK: 5'AMP-activated protein kinase; ATG: autophagy related; CCl4: carbon tetrachloride; CFS: cell-free supernatant; CMA: chaperone-mediated autophagy; CRC: colorectal cancer; EPS: L. plantarum H31 exopolysaccharide; HD: Huntington disease; HFD: high-fat diet; HPV: human papillomavirus; IFNG/IFN-γ: interferon gamma; IL6: interleukin 6; LGG: L. rhamnosus GG; LPS: lipopolysaccharide; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; PD: Parkinson disease; Pg3G: pelargonidin-3-O-glucoside; PI3K: phosphoinositide 3-kinase; PolyQ: polyglutamine; ROS: reactive oxygen species; SCFAs: short-chain fatty acids; SLAB51: a novel formulation of lactic acid bacteria and bifidobacteria; Slp: surface layer protein (of acidophilus NCFM); SNCA: synuclein alpha; ULK1: unc-51 like autophagy-activating kinase 1; YB: B. longum subsp. infantis YB0411; YFP: yeast fermentate prebiotic.

Derivatives of postbiotics (cell wall constituents) from Bacillus subtilis (LCBS1) relieve soybean meal-induced enteritis in bullfrog (Aquarana catesbeianus).

Soybean meal (SM) serves as a primary alternative to fish meal in aquafeeds. However, a high-SM diet may result in intestinal injury. Our previous study demonstrated the probiotic effects of heat-inactivated Bacillus subtilis (LCBS1) on bullfrogs (Aquarana catesbeianus) fed a high-SM diet, probably attributed to the bioactive constituent of cell wall. Therefore, in this study, the main constituents of cell wall from LCBS1, including peptidoglycan (PGN), lipoteichoic acid (LTA), cell wall protein (CWP), and whole cell wall (WCW), were extracted and added to a high-SM (~55 %) diet to investigate their probiotic effects on bullfrogs and reveal the possible mechanisms. The results indicated that bullfrogs fed the LTA of LCBS1 showed the highest weight gain, feed efficiency, and protein efficiency ratio. Additionally, the LTA of LCBS1 could activate the humoral immunity and modulate intestinal microbiota. It might activate JAK2-STAT3 and MAPK-ERK pathways, as well as up-regulate tlr5 gene to promote intestinal cell proliferation, thereby alleviating jejunal injury. The WCW of LCBS1 effectively increased the growth performance of bullfrogs by improving the humoral immunity, enhancing intestinal barrier function, and alleviating intestinal inflammatory response. The PGN and CWP of LCBS1 could stimulate the humoral immunity and enhance intestinal barrier function, but had no significant effect on the growth performance of bullfrogs. In conclusion, the LTA might be the primary bioactive constituent of heat-inactivated LCBS1, with the beneficial effects of promoting intestinal cell proliferation and enhancing intestinal barrier function, therefore alleviating the intestinal injury induced by SM on bullfrogs. This study establishes a theoretical basis for the efficient utilization of plant proteins by the application of postbiotics additive in aquafeed, which further saves the feed costs and promotes development of economically sustainable aquaculture.

Phosphorylation-dependent immunomodulatory properties of B.PAT polysaccharide isolated from Bifidobacterium animalis ssp. animalis CCDM 218.

A wide range of articles describe the role of different probiotics in the prevention or treatment of various diseases. However, currently, the focus is shifting from whole microorganisms to their easier-to-define components that can confer similar or stronger benefits on the host. Here, we aimed to describe polysaccharide B.PAT, which is a surface antigen isolated from Bifidobacterium animalis ssp. animalis CCDM 218 and to understand the relationship between its structure and function. For this reason, we determined its glycerol phosphate-substituted structure, which consists of glucose, galactose, and rhamnose residues creating the following repeating unit: To fully understand the role of glycerol phosphate substitution on the B.PAT function, we prepared the dephosphorylated counterpart (B.MAT) and tested their immunomodulatory properties. The results showed that the loss of glycerol phosphate increased the production of IL-6, IL-10, IL-12, and TNF-α in bone marrow dendritic cells alone and after treatment with Lacticaseibacillus rhamnosus GG. Further studies indicated that dephosphorylation can enhance B.PAT properties to suppress IL-1ß-induced inflammatory response in Caco-2 and HT-29 cells. Thus, we suggest that further investigation of B.PAT and B.MAT may reveal distinct functionalities that can be exploited in the treatment of various diseases and may constitute an alternative to probiotics.

Metal(loid)-gut microbiota interactions and microbiota-related protective strategies: A review.

Human exposure to metal(loid)s has dramatically increased over the past five decades, which has triggered public concern worldwide. Recently, gut microbiota has been considered a target for metal(loid)s, and some literature has reviewed the interactions between gut microbiota and heavy metal(loid)s (HMs) with high toxicity. However, whether there is an interaction between gut microbiota and metal(loid)s with essential roles or some normal functions are far from clear to date. Importantly, in addition to traditional probiotics that have been clarified to alleviate the adverse effect of HMs on the body, some novel probiotics, prebiotics, synbiotics, and postbiotics may also exhibit comparable or even better abilities of metal(loid) remediation. In this review, we mainly outline and discuss recent research findings on the metal(loid)-gut microbiota interactions and microbiota-related protective strategies.

Establishment of an Apical-Out Organoid Model for Directly Assessing the Function of Postbiotics.

In vitro organoids that mimic the physiological properties of in vivo organs based on threedimensional cell cultures overcome the limitations of two-dimensional culture systems. However, because the lumen of a typical intestinal organoid is internal, we used an apical-out intestinal organoid model in which the lumen that absorbs nutrients is outside to directly assess the function of postbiotics. A composite culture supernatant of Lactiplantibacillus plantarum KM2 and Bacillus velezensis KMU01 was used as a postbiotic treatment. Expression of COX-2 decreased in apical-out organoids co-treated with a lipopolysaccharide (LPS) and postbiotics. Expression of tight-junction markers such as ZO-1, claudin, and Occludin increased, and expression of mitochondrial homeostasis factors such as PINK1, parkin, and PGC1a also increased. As a result, small and large intestine organoids treated with postbiotics protected tight junctions from LPS-induced damage and maintained mitochondrial homeostasis through mitophagy and mitochondrial biogenesis. This suggests that an apical-out intestinal organoid model can confirm the function of food ingredients.