AG1, a Novel Synbiotic, Maintains Gut Barrier Function following Inflammatory Challenge in a Caco-2/THP1-Blue™ Co-Culture Model.

Nutritional interventions to reduce gastrointestinal (GI) permeability are of significant interest to physically active adults and those experiencing chronic health conditions. This in vitro study was designed to assess the impact of AG1, a novel synbiotic, on GI permeability following an inflammatory challenge. Interventions [AG1 (vitamins/minerals, pre-/probiotics, and phytonutrients) and control (control medium)] were fed separately into a human GI tract model (stomach, small intestine, and colon).

Poly(D,l-lactide-co-glycolide) particles are metabolised by the gut microbiome and elevate short chain fatty acids.

The production of short chain fatty acids (SCFAs) by the colonic microbiome has numerous benefits for human health, including maintenance of epithelial barrier function, suppression of colitis, and protection against carcinogenesis. Despite the therapeutic potential, there is currently no optimal approach for elevating the colonic microbiome's synthesis of SCFAs. In this study, poly(D,l-lactide-co-glycolide) (PLGA) was investigated for this application, as it was hypothesised that the colonic microbiota would metabolise PLGA to its lactate monomers, which would promote the resident microbiota's synthesis of SCFAs.

Ex Vivo Colonic Fermentation of NUTRIOSE Exerts Immuno-Modulatory Properties and Strong Anti-Inflammatory Effects.

NUTRIOSE (Roquette, Lestrem, France) is a resistant dextrin with well-established prebiotic effects. This study evaluated the indirect effects of pre-digested NUTRIOSE on host immune response and gut barrier integrity. Fecal samples from eight healthy donors were inoculated in a Colon-on-a-plate system (ProDigest, Ghent, Belgium) with or without NUTRIOSE supplementation.

Amino Acid Digestibility of Different Formulations of Torula Yeast in an In Vitro Porcine Gastrointestinal Digestion Model and Their Protective Effects on Barrier Function and Inflammation in a Caco-2/THP1Co-Culture Model.

Single-cell protein from torula yeast () grown on lignocellulosic biomass has been proven to be an excellent alternative protein source for animal feed. This study aimed to evaluate the amino acid (AA) digestibility by estimating intestinal absorption from three yeast-based ingredients, produced by cultivating on hydrolysate, using either mixed woody species (drum- (WDI) or spray-dried (WSI)) or corn dextrose (drum-dried (DDI)) as the carbon source. Further, the protective effect of intestinal digests on activated THP1-Blue™-induced epithelial damage and cytokine profile was evaluated.

Capacity of a Microbial Synbiotic To Rescue the Metabolic Activity of the Gut Microbiome following Perturbation with Alcohol or Antibiotics.

The human gut microbiome contributes crucial bioactive metabolites that support human health and is sensitive to perturbations from the ingestion of alcohol and antibiotics. We interrogated the response and recovery of human gut microbes after acute alcohol or broad-spectrum antibiotic administration in a gut model simulating the luminal and mucosal colonic environment with an inoculated human microbiome. Both alcohol and antibiotic treatments reduced the production of major short-chain fatty acids (SCFAs) (acetate, propionate, and butyrate), which are established modulators of human health.

Investigation of Enterogermina's Protective and Restorative Mechanisms on the Gut Microbiota with PPI, Using SHIME Technology.

Proton pump inhibitors (PPIs) are commonly prescribed medications associated with changes in the gut microbiome and dysbiosis when used long-term. Probiotics, such as Enterogermina (containing four strains of ) reduce side effects from triple therapy with PPI+antibiotics. We aim to assess the ability of this probiotic in preventing and/or treating the dysbiosis induced by PPI use.

The Modulation of Chaihu Shugan Formula on Microbiota Composition in the Simulator of the Human Intestinal Microbial Ecosystem Technology Platform and its Influence on Gut Barrier and Intestinal Immunity in Caco-2/THP1-Blue™ Cell Co-Culture Model.

The traditional Chinese medicine (TCM)-Chaihu Shugan Formula (CSF), consisting of several Chinese botanical drugs like Bupleurum, is derived from the ancient Chinese pharmacopeia. It has been used for more than thousands of years in various suboptimal health statuses and diseases induced by chronic stress based on empirical therapy. Recent studies confirm the role of CSF in the development of many diseases, including depression, stress-induced hepatic injury and tumors.

Influence of probiotic bacteria on gut microbiota composition and gut wall function in an model in patients with Parkinson's disease.

We report here the potential role of a 4-strain probiotic suspension for use with patients with Parkinson's disease (PD). Stool samples from a group of three patients with diagnosed PD were used to create microbiotas in an gut model. The effects of dosing with an oral probiotic suspension (Symprove) on bacterial composition and metabolic activity in the microbiotas was evaluated over 48 h and compared with healthy controls.

Water Kefir and Derived Pasteurized Beverages Modulate Gut Microbiota, Intestinal Permeability and Cytokine Production In Vitro.

Fermentation is an ancient food preservation process, and fermented products have been traditionally consumed in different cultures worldwide over the years. The interplay between human gut microbiota, diet and host health is widely recognized. Diet is one of the main factors modulating gut microbiota potentially with beneficial effects on human health.

Chitin Glucan Shifts Luminal and Mucosal Microbial Communities, Improve Epithelial Barrier and Modulates Cytokine Production In Vitro.

The human gut microbiota has been linked to the health status of the host. Modulation of human gut microbiota through pro- and prebiotic interventions has yielded promising results; however, the effect of novel prebiotics, such as chitin-glucan, on gut microbiota-host interplay is still not fully characterized. We assessed the effect of chitin-glucan (CG) and chitin-glucan plus (CGB) on human gut microbiota from the luminal and mucosal environments in vitro.

A Cranberry Concentrate Decreases Adhesion and Invasion of (AIEC) LF82 In Vitro.

While many beneficial host-microbiota interactions have been described, imbalanced microbiota in the gut is speculated to contribute to the progression and recurrence of chronic inflammatory diseases such as Crohn's disease (CD). This in vitro study evaluated the impact of a cranberry concentrate Type M (CTM) on adherent-invasive (AIEC) LF82, a pathobiont associated with CD. Different stages of pathogenic infection were investigated: (i) colonization of the mucus layer, and (ii) adhesion to and (iii) invasion of the epithelial cells.

Inclusion of small intestinal absorption and simulated mucosal surfaces further improve the Mucosal Simulator of the Canine Intestinal Microbial Ecosystem (M-SCIME™).

While a large set of in vitro models are available to study the effects of specific food ingredients (e.g. pre- and probiotics) on the human gut microbiome, the availability of such models for companion animals is limited.

A 4-strain probiotic supplement influences gut microbiota composition and gut wall function in patients with ulcerative colitis.

Symprove, a multi-strain probiotic, has been shown to exert a mild anti-inflammatory effect in patients with ulcerative colitis (UC). We examined stool samples from 3 patients with UC in order to create microbiotas in an in-vitro gut model. The effects of Symprove on bacterial diversity and metabolic activity in the microbiotas was evaluated over 48 h.

A Novel Non-Digestible, Carrot-Derived Polysaccharide (cRG-I) Selectively Modulates the Human Gut Microbiota while Promoting Gut Barrier Integrity: An Integrated in Vitro Approach.

Modulation of the gut microbiome as a means to improve human health has recently gained increasing interest. In this study, it was investigated whether cRG-I, a carrot-derived pectic polysaccharide, enriched in rhamnogalacturonan-I (RG-I) classifies as a potential prebiotic ingredient using novel in vitro models. First, digestion methods involving α-amylase/brush border enzymes demonstrated the non-digestibility of cRG-I by host-derived enzymes versus digestible (starch/maltose) and non-digestible controls (inulin).

A Bacteriophage Cocktail Eliminates Typhimurium from the Human Colonic Microbiome while Preserving Cytokine Signaling and Preventing Attachment to and Invasion of Human Cells by In Vitro.

Nontyphoidal strains continue to be a major cause of foodborne illness globally. One intriguing approach to reducing the risk of salmonellosis is the direct ingestion of phages targeting to enhance natural gut resilience and provide protection during foodborne disease outbreaks. We evaluated the ability of a prophylactically administered bacteriophage cocktail, the foodborne outbreak pill (FOP) targeting O157:H7, and to resolve a infection in the Simulator of the Human Intestinal Microbial Ecosystem (SHIME), a simulated gut platform populated by the human intestinal microbiome of healthy donors.

Mepazine Inhibits RANK-Induced Osteoclastogenesis Independent of Its MALT1 Inhibitory Function.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is an intracellular cysteine protease (paracaspase) that plays an integral role in innate and adaptive immunity. The phenothiazine mepazine has been shown to inhibit the proteolytic activity of MALT1 and is frequently used to study its biological role. MALT1 has recently been suggested as a therapeutic target in rheumatoid arthritis.

Unusual Lipid A from a Cold-Adapted Bacterium: Detailed Structural Characterization.

Colwellia psychrerythraea 34H is a Gram-negative cold-adapted microorganism that adopts many strategies to cope with the limitations associated with the low temperatures of its habitat. In this study, we report the complete characterization of the lipid A moiety from the lipopolysaccharide of Colwellia. Lipid A and its partially deacylated derivative were completely characterized by high-resolution mass spectrometry, NMR spectroscopy, and chemical analysis.

TRAF2 multitasking in TNF receptor-induced signaling to NF-κB, MAP kinases and cell death.

Tumor Necrosis Factor (TNF) is a potent inflammatory cytokine that exerts its functions through the activation of two distinct receptors, TNFR1 and TNFR2. Both receptors can activate canonical NF-κB and JNK MAP kinase signaling, while TNFR2 can also activate non-canonical NF-κB signaling, leading to numerous changes in gene expression that drive inflammation, cell proliferation and cell survival. On the other hand, TNFR1 also activates signaling pathways leading to cell death by either apoptosis or necroptosis, depending on the cellular context.

Receptor proximal kinases in NF-κB signaling as potential therapeutic targets in cancer and inflammation.

Many signaling pathways leading to activation of transcription factors and gene expression are characterized by phosphorylation events mediated by specific kinases. The transcription factor NF-κB plays a key role in multiple cellular processes, including immune signaling, inflammation, development, proliferation and survival. Dysregulated NF-κB activation is associated with autoimmunity, chronic inflammation and cancer.

The biology of A20-binding inhibitors of NF-kappaB activation (ABINs).

The family of A20-Binding Inhibitors of NF-kappaB (ABINs) consists of three proteins, ABIN-1, ABIN-2 and ABIN-3, which were originally identified as A20-binding proteins and inhibitors of cytokines and Lipopolysaccharide (LPS) induced NF-kappaB activation. ABIN family members have limited sequence homology in a number of short regions that mediate A20-binding, ubiquitin-binding, and NF-kappaB inhibition. The functional role of A20 binding to ABINs remains unclear, although an adaptor function has been suggested.

IκB kinase ε (IKKε): a therapeutic target in inflammation and cancer.

The innate immune system forms our first line of defense against invading pathogens and relies for a major part on the activation of two transcription factors, NF-κB and IRF3. Signaling pathways that activate these transcription factors are intertwined at the level of the canonical IκB kinases (IKKα, IKKβ) and non-canonical IKK-related kinases (IKKε, TBK1). Recently, significant progress has been made in understanding the function and mechanism of action of IKKε in immune signaling.

A20 inhibits LUBAC-mediated NF-κB activation by binding linear polyubiquitin chains via its zinc finger 7.

Linear polyubiquitination of proteins has recently been implicated in NF-κB signalling and is mediated by the linear ubiquitin chain assembly complex (LUBAC), consisting of HOIL-1, HOIP and Sharpin. However, the mechanisms that regulate linear ubiquitination are still unknown. Here, we show that A20 is rapidly recruited to NEMO and LUBAC upon TNF stimulation and that A20 inhibits LUBAC-induced NF-κB activation via its C-terminal zinc-finger 7 (ZF7) domain.

No ubiquitin anchors and fully RIGged.

Unanchored chains of ubiquitin have recently been proposed to play a role in signaling. In this issue of Immunity, Jiang et al. (2012) demonstrate that binding of free polyubiquitin to the viral RNA sensors RIG-I and MDA5 leads to their oligomerization and activation.

Linear ubiquitination in NF-κB signaling and inflammation: What we do understand and what we do not.

Despite its small size, ubiquitin is one of the most versatile signaling molecules in the cell and affects distinct cellular processes. It forms the building block of a repertoire of posttranslational modifications of cellular proteins, ranging from the attachment of a single ubiquitin to ubiquitin chains of different linkage. Proteins that contain ubiquitin chain-specific ubiquitin-binding domains recognize different types of ubiquitination and determine the mode of signaling of modified proteins.

TAX1BP1, a ubiquitin-binding adaptor protein in innate immunity and beyond.

The innate immune system senses and protects against invading microorganisms and endogenous danger signals by triggering inflammatory and antimicrobial responses. However, dysregulation of these pathways, which involve the transcription factors nuclear factor-κB (NF-κB) and interferon regulatory factor (IRF) 3, can lead to severe inflammatory diseases. Tax1-binding protein 1 (TAX1BP1) plays a key role in the negative regulation of NF-κB and IRF3 signaling by acting in concert with the ubiquitin-editing enzyme A20.