Intestinal Cells Research Articles

Trichinella spiralis excretory/secretory proteins mediated larval invasion via inducing gut epithelial apoptosis and barrier disruption.

Intestinal larva invasion is a crucial step of Trichinella spiralis infection. Intestinal infective larvae (IIL) and their excretory/secretory proteins (ESP) interact with gut epithelium, which often results in gut epithelium barrier injuries. Previous studies showed when T. spiralis invaded intestinal epithelium cells, the IIL ESP disrupted the tight junctions (TJs) of Caco-2 monolayer, but the mechanism is not clear. The IIL ESP might cause gut epithelial apoptosis, weaken the gut barrier and aid the larval invasion. The aim of this study was to investigate whether T. spiralis IIL ESP participate in enterocyte apoptosis and disrupt gut epithelial barrier to promote the larval invasion. Cell viability was assessed by CCK-8 assay and the results showed that 200 μg/ml of IIL ESP incubated with Caco-2 cells for 18 h inhibited the Caco-2 cell viability. The results of trans-epithelial electrical resistance (TEER) and FITC-dextran showed that IIL ESP decreased the TEER, increased FITC-dextran flux in Caco-2 monolayer. qPCR, Western blot and immunofluorescence test (IFT) showed that IIL ESP decreased the mRNA and protein expression of TJs (ZO-1, E-cad, Occludin and Claudin-1). The IIL ESP-induced Caco-2 cell apoptosis was observed by DAPI, Hoechst 33358, TUNEL and Annexin V/PI staining. Besides, flow cytometry revealed an increasing apoptosis rate in Caco-2 cells after the IIL ESP treatment. qPCR and Western blot analysis indicated that IIL ESP activated caspases (Caspase 3, Caspase 9 and Caspase 8), up-regulated the pro-apoptotic factors (Bax and Cytochrome c) and down-regulated the anti-apoptosis molecule Bcl-2. Interestingly, pretreatment of Caco-2 cells with apoptosis inhibitor Z-VAD-FMK abrogated and recovered the barrier function of Caco-2 monolayer destroyed by IIL ESP. Furthermore, the Z-VAD-FMK pretreatment also impeded the in vitro larva invasion of Caco-2 monolayer. T. spiralis IIL ESP induced gut epithelial apoptosis, reduced the TJs expression, damaged gut epithelial integrity and barrier function, and promoted larval invasion. These findings provided a basis of further understanding the interaction mechanism between T. spiralis and host gut epithelium, and they were valuable to the development new prevention and therapeutic strategy of early T. spiralis infection.

A Multipotent PROX1+ Tumor Stem/Progenitor Cell Population Emerges During Intestinal Tumorigenesis and Mediates Radioresistance in Colorectal Cancer.

Colorectal carcinoma (CRC) progression is associated with an increase in PROX1+ tumor cells, which exhibit features of CRC stem cells and contribute to metastasis. Here, we aimed to provide a better understanding to the function of PROX1+ cells in CRC, investigating their progeny and their role in therapy resistance. PROX1+ cells in intestinal adenomas of ApcMin/+ mice expressed intestinal epithelial and CRC stem cell markers, and cells with high PROX1 expression could both self-renew tumor stem/progenitor cells and contribute to differentiated tumor cells. Most PROX1-lineage traced tumor cells were stem/progenitor cells, which can supply cells to multiple intestinal tumor cell lineages, whereas most lineage-traced LGR5+ tumor cells were enterocytes, indicating that PROX1+ and LGR5+ tumor stem cells have distinct differentiation programs. Although the PROX1+ tumor cells proliferated slower than PROX1- cells, irradiation increased the proportion of PROX1+ cells in human CRC cell lines, patient-derived organoids, and tumor xenografts. Furthermore, transcripts related to DNA damage repair (DDR) were enriched in PROX1+ vs. PROX1- cells in adenomas and in CRC tumor cells from patients. Experiments with PROX1 silencing and overexpression indicated that PROX1 expression enhances CRC cell colony formation following irradiation. PROX1 interacted with DDR proteins, including components of non-homologous end-joining (NHEJ) and base excision repair, and inhibition of NHEJ repair led to a decreased proportion of PROX1+ cells following irradiation. In conclusion, PROX1+ cells are irradiation-resistant tumor stem/progenitor cells capable of self-renewal and differentiation. DDR inhibitors could represent a strategy to target the treatment-resistant PROX1+ tumor stem cells.

A 37-Color Spectral Flow Cytometric Panel to Assess Transcription Factors and Chemokine Receptors in Human Intestinal Lymphoid Cells.

We have developed a 37-color spectral flow cytometry panel to assess the phenotypical differentiation of innate and adaptive immune lymphoid subsets within human intestinal tissue. In addition to lineage markers for identifying innate lymphoid cells (ILC), TCRγδ, MAIT (mucosal-associated invariant T), natural killer (NK), CD4+ and CD8+ T cells, we incorporated markers of differentiation and activation (CD45RA, CD45RO, CD25, CD27, CD38, CD39, CD69, CD103, CD127, CD161, HLA-DR, CTLA-4 [CD152]), alongside transcription factors (Bcl-6, FoxP3, GATA-3, Helios, T-bet, PU.1 and RORγt) and chemokine receptors (CCR4, CCR6, CCR7, CXCR3, and CXCR5). Additionally, Granzyme B and Ki-67 were included to assess cytotoxicity and proliferation potential of the different subsets. This panel is currently used for in-depth immunophenotyping in endoscopic biopsies and peripheral blood mononuclear cells (PBMC) from inflammatory bowel disease (IBD) patients. Distinguished from other OMIP papers, the comprehensive detection of both transcription factors and chemokine receptors facilitates the efficient assessment of several subsets, particularly CD4+ T helper cells, and its potential application extends to both tissue and circulation.

Plastic nanoparticle toxicity is accentuated in the immune-competent inflamed intestinal tri-culture cell model

Introduction: Important cell-based models of intestinal inflammation have been advanced in hopes of predicting the impact of nanoparticles on disease. We sought to determine whether a high level and extended exposure of nanoplastic might result in the added intestinal inflammation caused by nanoplastic reported in a mouse model of irritable bowel disease. Methods: The cell models consist of a Transwell©-type insert with a filter membrane upon which lies a biculture monolayer of Caco-2 and HT29-MTX-E12 made up the barrier cells (apical compartment). This monolayer was exposed to digested 40 nm diameter polymethacrylate (PMA) with surface-functionalized COOH (PMA-) or NH2 (PMA+) at a ‘low level’ (143 µg/cm2 monolayer surface area) or ‘high level’ (571 µg/cm2) for 24 or 48 h. Beyond the apical compartment in the well of the tissue culture plate, was a monolayer of macrophages, previously differentiated from THP-1 cells (basolateral compartment). Thus, the immune competent tri-cultures were examined as two models: healthy and inflamed. The inflamed model, the barrier cell monolayer having been previously activated with IFN-γ and the macrophages having been previously activated with IFN-γ and LPS expressed a greater secretion of pro-inflammation cytokines. Results: Sedimentation, Diffusion and Dosimetry model (ISDD) simulated that 8%–12% of the PMA was deposited onto the barrier cell monolayer in 24–48-h. The structure of the barrier cells in the inflamed model was disorganized for both PMA, high level, 48-h experiments. While neither the amount of PMA nor the exposure duration influenced the lactate dehydrogenase (LDH) secretion in the healthy model, only the high levels of both PMA- and PMA+ in 48-h exposure experiments resulted in a significantly increased LDH secreted by the barrier cells in the inflamed model, compared to inflamed control. This study is the first to show an additive inflammation of nanoplastic in an inflamed intestinal model of the intestine.

Relevance of mouse and human IBD patients-derived colon organoids to investigate intestinal macrophage differentiation.

The gastrointestinal tract is a remarkable example of complex biology, with a constant dialogue between the intestinal epithelium, in close contact with the microbiota, and the immune cells that protect the gut from infection. Organoids have revolutionized our approach to modelling the intestinal cellular compartment and have opened new avenues for unravelling the mechanisms involved in intestinal homeostasis and chronic pathogenesis such as inflammatory bowel disease. To date, few models have been established to explore the role of the colon, which is however the main site of inflammation in ulcerative colitis (UC). Here, we used conditioned media produced by colon organoids (OCM) from mice or human (control and UC patients) to investigate the relationship between macrophages and the colon epithelium. We addressed transcriptomic profiles of OCM-stimulated bone marrow-derived macrophages and found that these cells exhibited a unique anti-inflammatory signature distinct from that of conventional in vitro IL-4/IL-13 M2 differentiated macrophages. In addition, OCM induced a clear CD5 antigen-like-mediated immunoregulatory effect characterized by a significant reduction in LPS-induced iNOS expression. In line, OCM from human colons inhibited LPS-dependent inflammatory cytokine expression in human monocytes-derived macrophages. Interestingly, the inflammatory marker CD68 was reduced by OCM from control patients but not from UC patients, suggesting epithelial dysfunction in UC patients. Our results report new regulatory mechanisms in the colon and highlight the importance of developing new in vitro models to better characterize the relationship between the intestinal epithelium and immune mucosal cells.

Highly Potent New Probiotic Strains from Traditional Turkish Fermented Foods.

Traditional Turkish fermented foods like boza, pickles, and tarhana are recognized for their nutritional and health benefits, yet the probiotic potential of lactic acid bacteria (LAB) strains isolated from them remains underexplored. Sixty-six LAB strains were isolated from fermented foods using bacterial morphology, Gram staining, and catalase activity. The isolates were differentiated at strain level by RAPD-PCR (Random Amplification of Polymorphic DNA-Polymerase Chain Reaction) and twenty-five strains were selected for further evaluation of acid and bile salt tolerance. Among these, ten strains exhibited high tolerance and were subsequently assessed for adhesion to Caco-2 colorectal carcinoma cells, antimicrobial activity, exopolysaccharide (EPS) production, lysozyme resistance, and hemolytic activity. Using k-means clustering, three strains: Lactiplantibacillus plantarum ES-3, Pediococcus pentosaceus N-1, and Enterococcus faecium N-2 demonstrated superior probiotic characteristics, including significant acid (100% survival at pH3.0) and 0.3% bile salt tolerance (57%, 64%, 67%), strong adhesion to intestinal cells (65%, 88%, 91%), high lysozyme resistance (88%, 88%, 77%), and produced high amounts of EPS. These strains show promising potential as probiotics and warrant further investigation to confirm their functional properties and potential applications.

Differential Enhancement of Fat-Soluble Vitamin Absorption and Bioefficacy via Micellization in Combination with Selected Plant Extracts In Vitro.

Background/Objectives: Individuals with special metabolic demands are at risk of deficiencies in fat-soluble vitamins, which can be counteracted via supplementation. Here, we tested the ability of micellization alone or in combination with selected natural plant extracts to increase the intestinal absorption and bioefficacy of fat-soluble vitamins. Methods: Micellated and nonmicellated vitamins D3 (cholecalciferol), D2 (ergocalciferol), E (alpha tocopheryl acetate), and K2 (menaquionone-7) were tested in intestinal Caco-2 or buccal TR146 cells in combination with curcuma (Curcuma longa), black pepper (Piper nigrum), or ginger (Zingiber officinale Roscoe) plant extracts. The vitamin uptake was quantified via HPLC-MS, and bioefficacy was assessed via gene expression analyses or the Griess assay for nitric oxide generation. Results: Micellization increased the uptake of vitamin D into buccal and intestinal cells, with vitamin D3 being more efficient than vitamin D2 in increasing the expression of genes involved in calcium transport. The micellization of vitamin E acetate increased its uptake and conversion into biologically active free vitamin E in intestinal cells only. The vitamin K2 uptake into buccal and intestinal cells was increased via micellization. Plant extracts increased the uptake of select micellated vitamins, with no plant extract being effective in combination with all vitamins. The curcuma extract increased the uptake of vitamins D2/D3 but not their bioefficacy. Black pepper and ginger extracts increased the uptake of vitamin E acetate into intestinal cells but failed to increase its conversion into free vitamin E. The ginger extract augmented the uptake of vitamin K2 and increased NO generation additively. Conclusions: Our data substantiate the positive effects of micellization on fat-soluble vitamin absorption and bioefficacy in vitro. While the application of plant extracts in addition to micellization to further increase bioefficacy is an interesting approach, further studies are warranted to understand vitamin-specific interactions and translation into increased bioefficacy.

Evolution and therapeutic potential of glucagon-like peptide 2 analogs.

Glucagon-like peptide 2 (GLP-2) is a proglucagon-derived peptide released by intestinal endocrine cells. However, its therapeutic potential is limited by rapid inactivation via dipeptidyl peptidase-IV. The elucidation of three-dimensional structures of G-protein-coupled receptors, including GLP-2 receptor, has facilitated the rational design of novel peptide therapeutics. Recent studies have explored various structural modifications based on the structure of GLP-2, such as amino acid substitution, lipidation, and fusion with proteins, to extend the half-life of GLP-2 and enhance its biological activity. One promising avenue involves the development of multifunctional molecules targeting multiple pharmacological systems to boost therapeutic efficacy. This paper reviews the recent advancements in understanding GLP-2, including its physiological roles and structure-activity relationships, and evaluates the development prospects of GLP-2 analogs.

The proneural transcription factor Atoh1 promotes odontogenic differentiation in human dental pulp stem cells (DPSCs)

BackgroundBioengineering of human teeth for replacement is an appealing regenerative approach in the era of gene therapy. Developmentally regulated transcription factors hold promise in the quest because these transcriptional regulators constitute the gene regulatory networks driving cell fate determination. Atonal homolog 1 (Atoh1) is a transcription factor of the basic helix-loop-helix (bHLH) family essential for neurogenesis in the cerebellum, auditory hair cell differentiation, and intestinal stem cell specification. The functional versatility of Atoh1 prompted us to test the possibility that Atoh1 may intersect the dental pulp stem cell (DPSC) gene regulatory network governing odontogenic differentiation.MethodsWe isolated DPSCs from human dental pulps and treated the cells with a replication-deficient adenoviral vector to achieve robust ectopic expression of Atoh1, following which the growth and odontogenic differentiation profiles of DPSCs were characterized.ResultsDPSCs harboring the Atoh1 expression vector exhibited an approximately 3,000-fold increase in the expression of Atoh1 compared to the negative control, leading to increased DPSC proliferation in the growth medium (P < 0.05). In the odontogenic medium, Atoh1 caused an early induction of BMP2 (P < 0.001) followed by a late induction of BMP7 (P < 0.01) and increased Wnt signaling (P < 0.01). The increased BMP/Wnt signaling led to up to 8-fold increased expression of the master osteogenic transcription factor Osterix (P < 0.005) while exhibiting no significant effect on Runx2 or Dlx5, which are abundantly expressed in DPSCs. Atoh1 stimulated expression of type I collagen (P < 0.005) and small integrin-binding ligand, N-linked glycoproteins (SIBLINGs) such as bone sialoprotein (P < 0.001), dentin matrix protein 1 (P < 0.05), dentin sialophosphoprotein (P < 0.005), and osteopontin (P < 0.001), resulting in increased dentin matrix mineralization (P < 0.05). The odontogenic phenotype is associated with metabolic remodeling marked by enhanced glycolytic flux and attenuated mitochondrial metabolic enzyme activities.ConclusionsAtoh1, despite being a proneural transcription factor in development, possesses a novel odontogenic function upon ectopic expression in DPSCs. This in vitro study demonstrates a novel odontogenic mechanism mediated by ectopic expression of the transcription factor Atoh1 in human DPSCs. The finding may offer an innovative strategy for gene-based regeneration of the pulp-dentin complex.

Transcytosis of T4 Bacteriophage Through Intestinal Cells Enhances Its Immune Activation.

Interactions between bacteriophages with mammalian immune cells are of great interest and most phages possess at least one molecular pattern (nucleic acid, sugar residue, or protein structure) that is recognizable to the immune system through pathogen associated molecular pattern (PAMP) receptors (i.e., TLRs). Given that phages reside in the same body niches as bacteria, they share the propensity to stimulate or quench immune responses depending on the nature of their interactions with host immune cells. While most in vitro research focuses on the outcomes of direct application of phages to immune cells of interest, the potential impact of their transcytosis through the intestinal barrier has yet to be considered. As transcytosis through intestinal cells is a necessary step in healthy systems for access by phage to the underlying immune cell populations, it is imperative to understand how this step may play a role in immune activation. We compared the activation of macrophages (as measured by TNFα secretion) following direct phage application to those stimulated by incubation with phage transcytosed through a polarized Caco2 epithelial barrier model. Our results demonstrate that phages capable of activating TNFα secretion upon direct contact maintain the stimulatory capability following transcytosis. Furthermore, activation of macrophages by a transcytosed phage is enhanced as compared to that occurring with an equivalent multiplicity of directly applied phage.

Beneficial Effects of In Vitro Reconstructed Human Gut Microbiota by Ginseng Extract Fermentation on Intestinal Cell Lines.

Oxidative stress caused by reactive oxygen species (ROS) affects the aging process and increases the likelihood of several diseases. A new frontier in its prevention includes bioactive foods and natural extracts that can be introduced by the diet in combination with specific probiotics. Among the natural compounds that we can introduce by the diet, Panax ginseng extract is one of the most utilized since it contains a vast number of bioactive molecules such as phenolic acids, flavonoids, and polysaccharides that have been shown to possess antioxidant, anti-ageing, anti-cancer, and immunomodulatory activity. In this work, the ability of a P. ginseng extract in combination with a probiotic formulation was taken into consideration to evaluate its effects on the modulation of in vitro reconstructed human gut microbiota (HGM). After evaluating the growth of the individual strains on the ginseng extract, we tested the in vitro reconstructed HGM setup (probiotics, minimal core, and whole community) using 2% w/v ginseng as the only carbon and energy source. The probiotic strains reached the highest growth, while the minimal core and the whole community showed almost the same growth. Specifically, the presence of the ginseng extract favors L. plantarum and B. animalis subsp. lactis among the probiotics, while B. cellulosilyticus prevails over the other strains in the minimal core condition. In the presence of both probiotics and minimal core strains, L. plantarum, B. animalis subsp. lactis, and B. cellulosilyticus reach the highest growth values. The bacterial metabolites produced during ginseng extract fermentation in the three conditions were administered to human intestinal epithelial cells (HT-29) to investigate a potential antioxidant effect. Remarkably, our results highlighted a significant reduction in the total ROS and a slightly reduction in the cytosolic superoxide anion content in HT-29 cells treated with bacterial metabolites deriving from ginseng extract fermentation by the whole community.

Influence of Mesalazine on Ferroptosis-Related Gene Expression in In Vitro Colorectal Cancer Culture.

Background/Objectives: Colorectal cancer (CRC) is one of the most common oncological disorders. Its fundamental treatments include surgery and chemotherapy, predominantly utilizing 5-fluorouracil (5-FU). Despite medical advances, CRC continues to present a high risk of recurrence, metastasis and low survival rates. Consequently, significant emphasis has been directed towards exploring novel types of cell death, particularly ferroptosis. Ferroptosis is characterized by iron imbalance and the accumulation of lipid peroxides and reactive oxygen species (ROS), leading to cellular damage and death. Thus, the discovery of safe inducers of ferroptosis, offering new hope in the struggle against CRC, remains crucial. In this study, we applied the concept of drug repositioning, selecting mesalazine (MES), a non-steroidal anti-inflammatory drug (NSAID), for investigation. Methods: The study was conducted on the colon cancer cell line DLD-1 and normal intestinal epithelial cells from the CCD 841 CoN cell line. Both cell lines were treated with MES solutions at concentrations of 10, 20, 30, 40, and 50 mM. Cytotoxicity was assessed using the MTT assay, while ferroptosis-related gene expression analysis was performed using oligonucleotide microarrays, with RT-qPCR used for validation. Results: MES effectively reduces the viability of DLD-1 cells while minimally affecting normal intestinal cells. Subsequent oligonucleotide microarray analysis revealed that MES significantly alters the expression of 56 genes associated with ferroptosis. Conclusions: Our results suggest that MES may induce ferroptosis in CRC, providing a foundation for further research in this area.

Oral Akkermansia muciniphila Biomimetic Nanotherapeutics for Ulcerative Colitis Targeted Treatment by Repairing Intestinal Epithelial Barrier and Restoring Redox Homeostasis.

The structural disruption of intestinal barrier and excessive reactive oxygen/nitrogen species (RONS) generation are two intertwined factors that drive the occurrence and development of ulcerative colitis (UC). Synchronously restoring the intestinal barrier and mitigating excess RONS is a promising strategy for UC management, but its treatment outcomes are still hindered by low drug accumulation and retention in colonic lesions. Inspired by intestine colonizing bacterium, we developed a mucoadhesive probiotic Akkermansia muciniphila-mimic entinostat-loaded hollow mesopores prussian blue (HMPB) nanotherapeutic (AM@HMPB@E) for UC-targeted therapy via repairing intestinal barrier and scavenging RONS. After oral administration, the negatively charged AM@HMPB@E specifically bind to the positively charged inflamed colon lesions via electrostatic interactions and Akkermansia muciniphila membrane-mediated bioadhesion mechanism. Subsequently, the superoxide dismutase (SOD)-, and catalase (CAT)-like HMPB eliminated RONS, thereby alleviating RONS-mediated inflammation and intestinal epithelial damage. Meanwhile, the UC-site locally released entinostat could repair the damaged intestinal epithelial barrier by inhibiting intestinal endothelial cell apoptosis and up-regulating the expression of tight junctions. Both in vitro and in vivo results shown that AM@HMPB@E not only exhibited an exceptional retention in the colitis site but also demonstrated superior therapeutic efficacy compared to the first-line drug sulfasalazine, as evidenced by the longer colon, less rectal bleeding and body weight loss. Collectively, our findings highlight the clinical application prospects of this synchronous nanotherapeutic strategy for UC treatment, offering a paradigm for the rational design of oral nanomedicine.

Air-liquid interface culture combined with differentiation factors reproducing intestinal cell structure formation in vitro.

Reproducing intestinal cells in vitro is important in pharmaceutical research and drug development. Caco-2 cells and human iPS cell-derived intestinal epithelial cells are widely used, but few evaluation systems can mimic the complex crypt-villus-like structure. We attempted to generate intestinal cells mimicking the three-dimensional structure from human iPS cells. After inducing the differentiation of iPS cells into intestinal organoids, these were dispersed into single cells and cultured two-dimensionally. An air-liquid interface culture was used, with CHIR99021, forskolin, and A-83-01 used as key compounds. Long-term culture was also performed by adding Wnt3a, Noggin, and RSPO1, which are frequently used in organoid culture. The air-liquid interface culture combined several compounds that successfully induced the formation of a crypt-villus-like structure, which grew rapidly at around day 6. The expression of pharmacokinetic genes such as CYP3A4 was also enhanced. The intestinal stem cells were efficiently maintained by the addition of Wnt3a, Noggin, and RSPO1. We were able to construct a crypt-villus-like structure on cell culture inserts, which is considered a very simple culture platform. This structure had characteristics extremely similar to living intestinal tissues and may have a superior homeostatic mechanism.

Review on Intestinal Stem Cell

The intestine performs the functions of absorption and protection. Located in the intestine, the intestinal stem cells play an important role in sustaining the intestinal homeostasis. The niche environment affects the intestinal stem cells functions via signaling, structural, and immune pathways. Active intestinal stem cells can differentiate into other intestinal cells and replenish them. This process is regulated by various signaling pathways, including Wnt, BMP, EGF and so on. In addition, other impact factors like aging and microbiota may also influence the intestinal homeostasis through affecting intestinal stem cells. Colorectal cancer, originating from abnormal intestinal stem, may be treated by multiple therapies

Effects of the Interactions Between Food Additive Titanium Dioxide and Matrices on Genotoxicity.

Titanium dioxide (TiO2), a white color food additive, is widely used in bakery products, candies, chewing gums, soups, and creamers. Concerns about its potential genotoxicity have recently emerged, particularly following the European Union's ban on its usage as a food additive due to its genotoxicity potential. Conflicting in vitro and in vivo results regarding its genotoxicity highlight the need for further in-depth investigation. Moreover, food additives can interact with food components or biological matrices, potentially altering their biological responses and genotoxicity. In this study, we evaluated the interactions between two different sizes of additive TiO2 particles and food or biological matrices, including albumin, fetal bovine serum (FBS), and glucose. The results showed that the hydrodynamic diameters of TiO2 increased upon interaction with albumin or FBS, but not with glucose. The presence of albumin or FBS reduced TiO2-induced cytotoxicity, oxidative stress, in vitro intestinal transport, and ex vivo intestinal absorption to untreated control levels, regardless of particle size. While TiO2 caused DNA damage in intestinal Caco-2 cells, the interactions with albumin or FBS significantly reduced the DNA damage to levels comparable to untreated controls. The DNA damage was closely related to oxidative stress caused by TiO2. These findings suggest that the interaction of TiO2 with albumin or FBS, resulting in increased hydrodynamic diameters, mitigates its cytotoxicity, oxidative stress, intestinal transport, and genotoxicity. Further investigation is required to fully understand the potential genotoxicity of TiO2 in food contexts.

Chemerin loss-of-function attenuates glucagon-like peptide-1 secretion in exercised obese mice.

To investigate the role of chemerin reduction in mediating exercise-induced Glucagon-like peptide-1 (GLP-1) secretion and the amelioration of pancreatic β-cell function in obesity. Obesity models were established using wild-type and chemerin systemic knockout mice, followed by 8 weeks of moderate-intensity continuous aerobic exercise training. Serum chemerin levels, GLP-1 synthesis, glucose tolerance, pancreatic β-cell function, structure, and apoptosis were assessed. In vitro experiments were conducted on STC-1 cells, derived from murine intestinal endocrine cells, to evaluate GLP-1 secretion following exogenous chemerin treatment. Additionally, colonic tissue inflammation and apoptosis were analyzed using qPCR and TUNEL staining. In obese wild-type mice, moderate-intensity aerobic exercise significantly reduced serum chemerin levels, enhanced GLP-1 secretion, and improved glucose tolerance, pancreatic β-cell structure, function, and apoptosis. These effects were absent in obese chemerin knockout mice. Exogenous chemerin treatment reduced GLP-1 secretion in STC-1 cells. Furthermore, the beneficial effects of exercise on colonic inflammation and apoptosis observed in wild-type mice were abolished in chemerin knockout mice. Reduction of chemerin is crucial for the beneficial effects of aerobic exercise on GLP-1 secretion and pancreatic β-cell function in obesity. The mechanisms behind these effects may involve improvements in colonic inflammation and apoptosis. These findings offer new insights into the molecular mechanisms through which exercise improves obesity-related metabolic dysfunction.

Bacteroides Fragilis Transplantation Reverses Reproductive Senescence by Transporting Extracellular Vesicles Through the Gut-Ovary Axis.

The diverse and dynamic population of microorganisms present in the gut microbiota may affect host health. There are evidences to support the role of gut microbiota as a key player in reproductive development. Unfortunately, the relationship between reproductive disorders caused by aging and gut microbiota remains largely unknown. Here, it is shown for the first time that gut microorganism Bacteroides fragilis (BF) transplantation ameliorates ovarian aging by transporting extracellular vesicles (EVs) through the gut-ovary axis. Mechanistically, miR-1246 is enriched in EVs derived from BF-treated intestinal cells, and these miR-1246-enriched EVs are transferred to ovaries, thereby effectively improving reproductive senescence by reducing oxidative stress in the ovaries. Specifically, miR-1246 reduces the ubiquitination of p62 and stabilizes the protein level of p62 by targeting E3 ligase SKP2. Then Keap1-Nrf2 complex is dissociated and Keap1 is recruited to form the p62-Keap1 complex. With the dissociation of Keap1-Nrf2 complex, Nrf2 is released and activated, thus promoting the transcription of antioxidant enzymes and relieving reproductive senescence. Collectively, the data indicates that intestinal cell-derived EVs serve as natural information carriers in the crosstalk between the gut and the ovary, and intestinal microorganism transplantation is a promising approach for the treatment of ovarian dysfunction diseases.

In Vitro and In Vivo Interventions Reveal the Health Benefits of Levan-Type Exopolysaccharide Produced by a Fish Gut Isolate Lactobacillus reuteri FW2.

Microorganisms synthesize diverse types of exopolysaccharides (EPSs). EPSs with varying structural and physical properties can demonstrate unique health benefits, which allow for their tailored applications as functional foods such as prebiotics. Levan, a fructose-based EPS, is gaining considerable attention as an effective prebiotic to support the growth of beneficial gut bacteria. Consequently, this enhances digestive health, boosts the immune system, and reduces the risk of chronic diseases. Unfortunately, limited studies are available on levan-type EPSs to demonstrate their role as prebiotics. Therefore, in this study, we conducted in vitro and in vivo experiments, concerning intestinal cell integrity and metabolic syndrome, to assess the therapeutic potential of levan derived from Lactobacillus reuteri FW2. The in vitro experimental results revealed that levan improved the survival of impaired HT-29 epithelial cells of the intestine and also exerted antioxidant effects. In the in vivo experiments, mice fed with levan-supplemented feed exhibited low body weight gain, blood glucose, and serum cholesterol levels compared to the control group. These findings highlight the biotherapeutic potential of L. reuteri FW2-derived levan for improving metabolic syndrome and its associated aspects. It also signifies the need for a further detailed investigation based on clinical trials to include levan in dietary supplements for improved health and well-being.

Combined BPA and DIBP Exposure Induced Intestinal Mucosal Barrier Impairment Through the Notch Pathway and Gut Microbiota Dysbiosis in Mice.

Bisphenol A (BPA) and diisobutyl (DIBP) phthalate are widely used as typical plasticizers in food packaging. Plasticizers can be released from polymers, migrate into food, and be ingested by humans, leading to various health problems. However, little research has investigated the combined toxicity of BPA and DIBP, particularly their intestinal toxicity. Our goal is to analyse the combined toxicity of BPA (50 mg/kg) and DIBP (500 mg/kg) on the intestines of KM mice. Additionally, we tried to find natural products that can inhibit or prevent the combined toxicity of BPA and DIBP. The results indicated that the combination of BPA and DIBP exposure resulted in a reduction of beneficial flora, an increase in D-Lac levels (136 ± 14 μmol/L), an increase in intestinal permeability, activation of the notch pathway, and a decline in intestinal stem cells (ISCs) to goblet cells, compared to single-exposure sources. Nevertheless, Rubus chingii Hu phenolic extract (RHPE) (200, 400 and 600 mg/kg) ameliorated the BPA and DIBP-induced intestinal microbiota disruption and intestinal mucosal barrier impairment by inhibiting the overactivation of the notch pathway. The results of this study highlight the potential risks to human health posed by the combination of BPA and DIBP and may help explain the potential pathways of enterotoxicity caused by combined ingestion.