Excessive intake of dietary fats is strongly associated with an increased risk of various chronic diseases, such as obesity, diabetes, hepatic metabolic disorders, cardiovascular disease, chronic intestinal inflammation, and certain cancers. A significant portion of the adverse effects of high-fat diet on disease risk is mediated through modifications in the gut microbiota. Specifically, high-fat diets are linked to reduced microbial diversity, an overgrowth of gram-negative bacteria, an elevated Firmicutes-to-Bacteroidetes ratio, and alterations at various taxonomic levels. These microbial alterations influence the intestinal metabolism of small molecules, which subsequently increases intestinal permeability, exacerbates inflammatory responses, disrupts metabolic functions, and impairs signal transduction pathways in the host. Consequently, diet-induced changes in the gut microbiota play a crucial role in the initiation and progression of chronic diseases. This review explores the relationship between high-fat diets and gut microbiota, highlighting their roles and underlying mechanisms in the development of chronic metabolic diseases. Additionally, we propose probiotic interventions may serve as a promising adjunctive therapy to counteract the negative effects of high-fat diet-induced alterations in gut microbiota composition.

Epidemiological evidence suggests that there is a direct relationship between the degree of obesity and acute pancreatitis severity. Intake of different fatty acids leads to different types of hyperlipidemias. Adipose degradation by pancreatic lipase generates different free fatty acids, which can exacerbate pancreatitis. Saturated fatty acids (SFAs) play an inflammatory role in human metabolic syndrome and obesity, whereas unsaturated fatty acids (UFAs) are "good fats" that are thought to enhance overall health status. However, it appears that serum UFAs correlate with severe acute pancreatitis. Additionally, the "obesity paradox" suggests that UFAs potentially minimize direct harm to the organ. This review provides an in-depth overview of the role of SFAs and UFAs in acute pancreatitis of hyperlipidemia and discusses potential prevention targets for severe acute pancreatitis.

Drug-induced liver injury (DILI) presents a major challenge not only in new drug development but also in post-marketing withdrawals and the safety of food, cosmetics, and chemicals. Experimental model organisms such as the rodents have been widely used for preclinical toxicological testing. However, the tension exists associated with the ethical and sustainable use of animals in part because animals do not necessarily inform the human-specific ADME (adsorption, dynamics, metabolism and elimination) profiling. To establish alternative models in humans, in vitro hepatic tissue models have been proposed, ranging from primary hepatocytes, immortal hepatocytes, to the development of new cell resources such as stem cell-derived hepatocytes. Given the evolving number of novel alternative methods, understanding possible combinations of cell sources and culture methods will be crucial to develop the context-of-use assays. This review primarily focuses on 3D liver organoid models for conducting. We will review the relevant cell sources, bioengineering methods, selection of training compounds, and biomarkers towards the rationale design of in vitro toxicology testing.

Lipopolysaccharide (LPS)-induced inflammation of lung tissues triggers irreversible alterations in the lung parenchyma, leading to fibrosis and pulmonary dysfunction. While the molecular and cellular responses of immune and connective tissue cells in the lungs are well characterized, the specific epithelial response remains unclear due to the lack of representative cell models. Recently, we introduced human embryonic stem cell-derived expandable lung epithelial (ELEP) cells as a novel model for studying lung injury and regeneration.

ELEPs were derived from the CCTL 14 human embryonic stem cell line through activin A-mediated endoderm specification, followed by further induction toward pulmonary epithelium using FGF2 and EGF. ELEPs exhibit a high proliferation rate and express key structural and molecular markers of alveolar progenitors, such as NKX2-1. The effects of Escherichia coli LPS serotype O55:B5 on the phenotype and molecular signaling of ELEPs were analyzed using viability and migration assays, mRNA and protein levels were determined by qRT-PCR, western blotting, and immunofluorescent microscopy.

We demonstrated that purified LPS induces features of a hybrid epithelial-to-mesenchymal transition in pluripotent stem cell-derived ELEPs, triggers the unfolded protein response, and upregulates intracellular β-catenin level through retention of E-cadherin within the endoplasmic reticulum.

Human embryonic stem cell-derived ELEPs provide a biologically relevant, non-cancerous lung cell model to investigate molecular responses to inflammatory stimuli and address epithelial plasticity. This approach offers novel insights into the fine molecular processes underlying lung injury and repair.

Obesity is associated with increased gut permeability, which contributes to a state of chronic low-grade inflammation. Obesity is also linked with altered neurocognitive functions, including impaired learning and memory. Whether these changes are secondary to neuroinflammation vs. other comorbidities associated with obesity is unknown. Here, we modeled the chronic low-grade inflammation that accompanies diet-induced obesity, but in the absence of obesity or consumption of an obesogenic diet. Male rats were implanted with intraperitoneal osmotic minipumps, continuously dispensing either saline (control) or lipopolysaccharide (LPS), an endotoxin produced in the gut that triggers inflammation when in circulation. Immunohistochemistry results revealed that LPS exposure led to neuroinflammation, with an increased number of Ionized Calcium-Binding Molecule 1 (Iba1+) cells in the amygdala and hippocampus in LPS rats vs. controls. Given that these brain regions are associated with impulse control, anxiety-like behavior, and learning and memory, we tested whether chronic LPS treatment impacted these behaviors. Interestingly, LPS exposure did not affect hippocampal-dependent memory in the Morris water maze, novel location recognition, or novel object in context memory tests, suggesting that neuroinflammation in the absence of obesity does not induce memory impairments. Further, chronic LPS significantly decreased anxiety-like behavior in the open field test and food impulsivity in an operant-based procedure. LPS animals also had significantly lower corticosterone and melatonin levels when compared to controls, which may contribute to these behavioral outcomes. These results suggest that the low-grade inflammation associated with obesity is not driving obesity-associated memory impairments but does reduce anxiety and food-motivated impulsive responses.

The pathogenesis of enteric viral infections is attributed to both viral replication and the resultant immune-inflammatory response. To recapitulate this complex pathophysiology, we engineer macrophage-augmented organoids (MaugOs) by integrating human macrophages into primary intestinal organoids. Echovirus 1, echovirus 6, rotavirus, seasonal coronavirus OC43 and SARS-CoV-2- known to directly invade the intestine- are used as disease modalities. We demonstrate that these viruses efficiently propagate in MaugOs and stimulate the host antiviral response. However, rotavirus, coronavirus OC43 and SARS-CoV-2, but not the two echoviruses, trigger inflammatory responses. Acetate, a microbial metabolite abundantly present in the intestine, potently inhibits virus-induced inflammatory responses in MaugOs, while differentially affecting viral replication in macrophages and organoids. Furthermore, we provide a proof-of-concept of combining antiviral agent with either anti-inflammatory regimen or acetate to simultaneously inhibit viral infection and inflammatory response in MaugOs. Collectively, these findings demonstrate that MaugOs are innovative tools for studying the complex virus-host interactions and advancing therapeutic development.

The importance of the microbiome, particularly the gut microbiota and its implications for health, is well established. However, an increasing number of studies further strengthen the link between an imbalanced gut microbiota and a greater predisposition to different diseases. The gut microbiota constitutes a fundamental ecosystem for maintaining human health. Its alteration, known as dysbiosis, is associated with a wide range of conditions, including intestinal, metabolic, immunological, or neurological pathologies, among others. In recent years, there has been a substantial increase in knowledge about probiotics-bacterial species that enhance health or address various diseases-with numerous studies reporting their benefits in preventing or improving these conditions. This review aims to analyze the most common pathologies resulting from an imbalance in the gut microbiota, as well as detail the most important and known gut probiotics, their functions, and mechanisms of action in relation to these conditions.

The multistrain probiotics' efficacy in ameliorating the endotoxemic effect in Lipopolysaccharide (LPS) challenged mice was evaluated with the agonist of anti-inflammatory peptide, neurotensin (NTS), especially targeting the inflammation of the gut and liver. Swiss Albino Mice (Female, 8 weeks old) were maintained in eight groups: Group I as Control, Group II-Group V were exposed to intraperitoneal (i.p.) LPS (1 mg/kg bw) for 5 days. After that, Group III and Group VI were administered probiotics orally (0.6 gm/kg bw/day), Group IV and Group VII with NTS receptor 1 (NTSR1) agonist PD149163 (50 µg/kg bw/day i.p.), and Group V and Group VIII co-administered with probiotics and PD149163 for 28 days. Group II (LPS-exposed) was maintained without any further treatment; mice of all the groups were sacrificed at day 34. In the LPS-exposed mice, endotoxemia was distinct from a significant (P < 0.001) increase of plasma pro-inflammatory cytokines (TNF-α; IL-6), a decrease of anti-inflammatory cytokine (IL-10), oxidative stress, and inflammation of the gut and liver. Increased serum transaminases indicated hepatic inflammation. A decreased population of the bifidobacteria and increased clostridia indicated microbiota dysbiosis. Probiotics when used as an adjunct along with PD149163 have shown better efficacy in inflammation modulation as reflected in the significantly decreased (P < 0.001) inflammatory mediators, oxidative stress, restoration of the beneficial bacterial population, along with a significant reduction in histopathological scores of the gut and the liver than when used alone. This study suggests probiotics could be used as an adjunct in clinical practice along with anti-inflammatory drugs for better therapeutic efficacy.

Overproduction of reactive oxygen species and antioxidant superoxide dismutases (SOD1, SOD2) dysregulation contribute to chronic inflammation such as generated in inflammatory bowel diseases (IBD). A kinetic redox shotgun proteomic strategy (OcSILAC for Oxidized cysteine Stable Isotope Labelling by Amino acids in Cell culture) was used to explore the lipopolysaccharide (LPS) effects including LPS-induced oxidation and inflammation cascades on a dedicated intestinal epithelial cell line (HT29-MD2) together with the potential mitigating role of a Mn-based SOD-mimic Mn1. While LPS induced transient oxidative damages at early times (15 min), cells incubated with Mn1 showed, in this time frame, a significantly reduced cysteine oxidation, highlighting Mn1 antioxidant properties. Over time, cysteine oxidation of LPS-treated cells was counteracted by an overexpression of antioxidant proteins (SOD1, NQO1) and a late (6 h) preponderant increase in SOD2 level. Mn1, when co-incubated with LPS, attenuated the level of most LPS-modified proteins, that is, proteins involved in the inflammatory response. Our results highlight Mn1 as a potentially effective antioxidant and anti-inflammatory agent to consider in the treatment of IBD, as well as a useful tool for exploring the interconnection between oxidative stress and inflammation.

This systematic review investigates gut bacterial diversity and composition in patients with Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS) and examines how these changes may contribute to cardiovascular complications.

A comprehensive search was conducted in PubMed, Web of Science, and Scopus up to March 2025. After removing duplicates, titles and abstracts were screened by two reviewers, and full texts were assessed for inclusion. Data extraction on study characteristics and outcomes was performed. Methodological quality was evaluated using the Joanna Briggs Institute checklist. α-diversity was assessed using richness and diversity indices, while β-diversity examined community structure differences. Meta-analysis was conducted using standardized mean differences (SMD) and confidence intervals (CIs), and heterogeneity was assessed with the Cochrane I2 test.

The review included 18 studies (16 adults, 2 pediatrics) examining the gut microbiome in OSAHS. Meta-analysis revealed significant reductions in α-diversity indices (Shannon, Chao1, observed species, ACE) in OSAHS patients, while Simpson's index showed no difference. β-diversity analyses showed distinct gut microbiome differences in OSA. Key differential bacteria included Bacteroides, Proteobacteria, Faecalibacterium, Ruminococcaceae, Megamonas, Oscillibacter, Dialister, Roseburia, and Lachnospira. Study quality was medium to high.

OSAHS is associated with significant gut microbiome alterations, including a reduction in beneficial bacteria and an increase in LPS-producing bacteria, leading to intestinal barrier dysfunction. These changes may contribute to systemic inflammation and elevate the risk of cardiovascular diseases.

This study was conducted to investigate the protective effects of chlorogenic acid (CGA) on intestinal health in broilers challenged with avian pathogenic Escherichia coli (APEC). One hundred and eighty one-day-old male broiler chicks were divided into three groups with six replicates of ten chicks each for a 21-day trial. The birds in the control and APEC groups were fed a basal diet, while birds in the CGA-treated group received a basal diet supplemented with 1000 mg/kg of CGA. At 14 days, birds in the APEC and CGA groups were administered with an APEC suspension Compared with the APEC group, CGA incorporation decreased mortality and cecal Escherichia coli colonies in bacterially challenged broilers (P < 0.05). Additionally, CGA reduced the relative weight of the heart, liver, kidney, gizzard, proventriculus, and intestine, as well as serum triglyceride level and alanine aminotransferase activity in APEC-challenged broilers (P < 0.05). Supplementing CGA reduced the concentrations of interferon-γ, tumor necrosis factor-α, interleukin-1β, and/or interleukin-6 in serum, duodenum, jejunum, and/or ileum in APEC-challenged broilers presumably through the inactivation of the toll-like receptor 4/myeloid differentiation factor 88 pathway (P < 0.05). CGA administration reduced serum diamine oxidase activity and d-lactate and endotoxin concentrations, but increased the ratio between villus height and crypt depth in duodenum and jejunum of APEC-infected chickens, accompanied by the restored intestinal expression of tight junction proteins (claudin-1, claudin-2, occludin, and zonula occludens-1) and genes involved in apoptosis (B cell lymphoma-2 associated X protein, B cell lymphoma-2, and cysteine-requiring aspartate protease 9) (P < 0.05). Additionally, CGA increased superoxide dismutase, glutathione peroxidase, and catalase activities, and glutathione levels in serum and intestinal mucosa, but inhibited the accumulation of intestinal malondialdehyde in APEC-challenged broilers possibly via activating the nuclear factor-erythroid 2-related factor-2/heme oxygenase-1 pathway (P < 0.05). The results suggested that CGA alleviated APEC-induced intestinal damage in broilers by inhibiting inflammation and oxidative stress. However, its potential application in practical poultry production is contingent upon both its efficacy and cost-effectiveness.

Irritable bowel syndrome (IBS) is a chronic, functional gastrointestinal disorder (FGID) which is characterized by chronic pain related to defecation and alteration in GI motility. Recent findings indicated that intestinal barrier dysfunction, hyperpermeability, oxidative stress, and inflammation play a role in IBS pathogenesis. Considering the antioxidant properties of Spirulina (Arthrospira) platensis (SP), this study aimed to investigate the effect of SP supplementation on Quality of life (QoL), disease severity, antioxidant capacity, oxidative stress index and intestinal permeability in constipation-dominant IBS (IBS-C) patients.

This study was a parallel randomized, double-blind, placebo-controlled clinical trial involving 60 IBS-C patients aged 18-50 years. The patients were given either 1 g SP (two capsules/day; each capsule contained 500 mg of SP) or placebo for 12 weeks. IBS-QoL, IBS-Severity system score (IBS-SSS), plasma total antioxidant capacity (TAC), malondialdehyde (MDA), and zonulin levels were measured at baseline and the end of the intervention. Univariate comparison and intention-to-treat (ITT) were used for analysis.

SP supplementation compared to placebo resulted in a significant increase in QoL score (7.05 ± 2.02 vs. - 1.57 ± 2.49; p = 0.008), TAC (145.27 ± 30.77 vs. -54.90 ± 45.72; p < 0.001) and decrease in IBS-SSS (-32.17 ± 8.96 vs. 1.07 ± 8.49; p = 0.002), MDA level (- 11.61 ± 2.57 vs. - 2.00 ± 2.24; p < 0.001) and zonulin level (- 0.22 ± 0.05 vs. 0.12 ± 0.07; p = 0.001). These results remained significant after adjusting for baseline values.

SP supplementation demonstrated a promising effect in the management of IBS. However, larger trials with a dose-dependent approach in IBS-C and other subtypes of IBS are warranted.

The study protocol was approved by the ethical committee at the Isfahan University of Medical Sciences (Registration No. IR.MUI.

REC.1401.370) and registered online at http://www.IRCT.ir (code: IRCT20140208016529N8, approved date 25.04.2023).

The high prevalence and disability rate of type 2 diabetes (T2D) caused a huge social burden to the world. Currently, new mechanisms and therapeutic approaches that may affect this disease are being sought. With in-depth research on the pathogenesis of T2D and growing advances in microbiome sequencing technology, the association between T2D and gut microbiota has been confirmed. The gut microbiota participates in the regulation of inflammation, intestinal permeability, short-chain fatty acid metabolism, branched-chain amino acid metabolism and bile acid metabolism, thereby affecting host glucose and lipid metabolism. Interventions focusing on the gut microbiota are gaining traction as a promising approach to T2D management. For example, dietary intervention, prebiotics and probiotics, faecal microbiota transplant and phage therapy. Meticulous experimental design and choice of analytical methods are crucial for obtaining accurate and meaningful results from microbiome studies. How to design gut microbiome research in T2D and choose different machine learning methods for data analysis are extremely critical to achieve personalized precision medicine.

Harnessing the effect of the cyclic GMP-AMP Synthase-STimulator of INterferon Genes (cGAS-STING) signaling pathway has emerged as a promising approach to developing novel strategies for the oral treatment of inflammatory bowel disease (IBD). In this work, we screened different cGAS-STING inhibitors in vitro in murine macrophages. Then, we encapsulated the cGAS-STING inhibitor H-151 within lipid nanocapsules (LNCs), owing to their inherent ability to induce the secretion of glucagon-like peptide 2 (GLP-2), a re-epithelizing peptide, upon oral administration. We demonstrated that our formulation (LNC(H-151)) could induce GLP-2 secretion and selectively target the cGAS-STING pathway and its downstream key markers (including TBK1 and pTBK1) while reducing the expression of pro-inflammatory cytokines associated with the cGAS-STING pathway (TNF-α and CXCL10) in murine macrophages. In an in vivo acute dextran sodium sulfate (DSS)-induced colitis mouse model, the oral administration of LNC(H-151) significantly reduced pro-inflammatory cytokines to levels comparable to the CTRL Healthy group while promoting mucosal healing. The therapeutic potential of this scalable and cost-effective nanomedicine warrants further investigation as an alternative for the oral treatment of IBD.

The study investigates the strain-specific immunomodulatory properties of live and thermally-inactivated (TI) lactic acid bacteria (LAB) derived from traditional Polish fermented foods, focusing on their potential as probiotics and postbiotics. LAB strains, known for their role in food fermentation, were assessed for their ability to influence cytokine production in THP-1 macrophages, maintain intestinal epithelial barrier integrity in Caco-2 monolayers, exhibit antioxidant activity, and produce specific organic acids and sugars. The research demonstrated that live LAB strains significantly upregulated the anti-inflammatory cytokine IL-10, particularly under inflammatory conditions, while TI strains exhibited notable antioxidant and anti-inflammatory properties. TI strains showed a greater ability to protect epithelial barrier function and reduce pro-inflammatory cytokine secretion than live strains, suggesting a promising role for postbiotics. The findings underscore the potential of LAB from fermented foods, demonstrating that postbiotic derivatives can differently influence inflammation compared to live bacteria, highlighting their potential as immune-enhancing agents, capable of modulating immune responses and offering therapeutic benefits against inflammation-related disorders. However, the limitations of in vitro models highlight the need for further in vivo and clinical studies to validate these effects and fully uncover the health benefits of these LAB strains for humans.

The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) have therapeutic effects in diabetes mellitus. Prior clinical studies suggest incretins are prognostic of adverse outcomes in critical illness. We investigated whether incretin levels indicate disease severity and clinical outcomes in patients with acute respiratory failure, a common cause of critical illness.

Retrospective cohort study.

ICUs in UPMC Health Systems hospitals within Western Pennsylvania.

Two hundred ninety-seven critically ill adults with acute respiratory failure.

None.

We measured GLP-1 and GIP levels in baseline samples collected at the time of study enrollment. We compared incretin levels across subgroups differing by severity of illness and investigated associations between incretins and markers of systemic host responses and intestinal permeability. In our primary analysis, we tested the association of each incretin level with 90-day mortality by logistic regression in unadjusted analyses and in analyses adjusted for age, Sequential Organ Failure Assessment score, and circulating interleukin-6 levels. GLP-1 levels were higher in nonsurvivors and patients with or at-risk for acute respiratory distress syndrome compared to those intubated for airway protection. GLP-1 levels also positively correlated with systemic immune response biomarkers but not with markers of intestinal permeability. GLP-1 levels positively correlated with mortality in unadjusted (odds ratio, 1.99 [1.55-2.56]; p < 0.01) and adjusted (2.02 [1.23-3.31]; p < 0.01) analyses. GIP levels were not associated with mortality or with host response biomarkers.

GLP-1 but not GIP levels were positively associated with systemic inflammation and mortality in critically ill patients with acute respiratory failure. Increased circulating GLP-1 levels may serve as prognostic biomarkers to identify patients who are likely to have worse outcomes.

Low-calorie sweeteners (LCSs) are popular sugar substitutes and have been shown to alter the gut microbiota, which raises concerns about potential impacts on intestinal permeability.

This study aimed to examine cross-sectional associations between LCS consumption and circulating biomarkers of intestinal permeability.

We analyzed data from 572 United States adults participating in the Cancer Prevention Study-3 Diet Assessment Substudy who provided ≤2 fasting blood samples, collected 6 mo apart, to measure biomarkers of intestinal permeability including antibodies to flagellin (anti-flagellin), lipopolysaccharide (anti-LPS), and total antibodies; and ≤6 24-h dietary recalls, collected over the course of 12 mo, to estimate average intake of LCS including aspartame, sucralose, acesulfame-potassium, and saccharin. Multivariable linear regression, adjusted for sociodemographic characteristics, lifestyle factors, and medical history, was used to examine associations between LCS consumption and levels of intestinal permeability biomarkers by comparing mean differences in biomarkers among lower (>0 to ≤50th percentile) (n = 158) and higher (>50th percentile) LCS consumers (n = 157) than nonconsumers. A linear trend across nonconsumers and the 2 consumption categories was evaluated using a continuous variable based on the median LCS intake (median = 0, 11.3, and 124.2 mg/d for non-, lower, and higher consumers, respectively).

Among the 572 study participants, the mean age was 52.5 y, 63.3% were female, 60.7% were on-Hispanic White, and 55.1% reported consuming LCS-containing products. Greater LCS consumption was not associated with anti-flagellin, anti-LPS, or total antibodies. Additionally, no associations between specific types of LCS and intestinal permeability biomarkers were observed.

The results of our study did not demonstrate an association between LCS consumption and intestinal permeability biomarkers. Further research with larger sample sizes and randomized controlled trials is needed to confirm our findings.

Plastic cutting boards are commonly used in food preparation, increasing human exposure to microplastics (MPs). However, the health implications are still not well understood.

The objective of this study was to assess the impacts of long-term exposure to MPs released from cutting boards on intestinal inflammation and gut microbiota.

MPs were incorporated into mouse diets by cutting the food on polypropylene (PP), polyethylene (PE), and willow wooden (WB) cutting boards, and the diets were fed to mice over periods of 4 and 12 wk. Serum levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α ), interleukin-10 (IL-10), lipopolysaccharide (LPS, an endotoxin), and carcinoembryonic antigen (CEA), along with ileum and colon levels of interleukin-1β (IL-1 β ), TNF-α , malondialdehyde (MDA), superoxide dismutase (SOD), secretory immunoglobulin A (sIgA), and myosin light chain kinase (MLCK), were measured using mouse enzyme-linked immunosorbent assay (ELISA) kits. The mRNA expression of mucin 2 and intestinal tight junction proteins in mouse ileum and colon tissues was quantified using real-time quantitative reverse transcription polymerase chain reaction. Fecal microbiota, fecal metabolomics, and liver metabolomics were characterized.

PP and PE cutting boards released MPs, with concentrations reaching 1,088 ± 95.0 and 1,211 ± 322 μ g / g in diets, respectively, and displaying mean particle sizes of 10.4 ± 0.96 vs. 27.4 ± 1.45 μ m . Mice fed diets prepared on PP cutting boards for 12 wk exhibited significantly higher serum levels of LPS, CRP, TNF-α , IL-10, and CEA, as well as higher levels of IL-1β , TNF-α , MDA, SOD, and MLCK in the ileum and colon compared with mice fed diets prepared on WB cutting boards. These mice also showed lower relative expression of Occludin and Zonula occludens-1 in the ileum and colon. In contrast, mice exposed to diets prepared on PE cutting boards for 12 wk did not show evident inflammation; however, there was a significant decrease in the relative abundance of Firmicutes and an increase in Desulfobacterota compared with those fed diets prepared on WB cutting boards, and exposure to diets prepared on PE cutting boards over 12 wk also altered mouse fecal and liver metabolites compared with those fed diets prepared on WB cutting boards.

The findings suggest that MPs from PP cutting boards impair intestinal barrier function and induce inflammation, whereas those from PE cutting boards affect the gut microbiota, gut metabolism, and liver metabolism in the mouse model. These findings offer crucial insights into the safe use of plastic cutting boards. https://doi.org/10.1289/EHP15472.

Endotoxin-driven systemic immune activation is a common hallmark across various clinical conditions. During acute critical illness, elevated plasma lipopolysaccharide triggers non-specific systemic immune activation. In addition, a compositional shift in the gut microbiota, including an increase in gut-luminal opportunistic pathogens, is observed. Whether a causal link exists between acute endotoxemia and abundance of gut-luminal opportunistic pathogens is incompletely understood. Here, we model acute, pathophysiological lipopolysaccharide concentrations in mice and show that systemic exposure promotes a 100-10'000-fold expansion of Klebsiella pneumoniae, Escherichia coli, Enterococcus faecium and Salmonella Typhimurium in the gut within one day, without overt enteropathy. Mechanistically, this is driven by a Toll-like receptor 4-dependent increase in gut-luminal oxygen species levels, which transiently halts microbiota fermentation and fuels growth of gut-luminal facultative anaerobic pathogens through oxidative respiration. Thus, systemic immune activation transiently perturbs microbiota homeostasis and favours opportunistic pathogens, potentially increasing the risk of infection in critically ill patients.

The developmental origins of health and disease (DOHaD) concept suggests that adverse conditions during gestation can influence the development and function of multiple organs, including the gastrointestinal tract. Maternal protein restriction (MPR) exposure has been associated with negative effects on reproduction, the endocrine system, and liver metabolic health. However, limited research has explored the impact of MPR on the offspring's intestinal morphophysiology. This study investigated the effects of gestational and lactational MPR on the duodenum and colon of young male offspring rats at postnatal (PND)21. We hypothesize that MPR affects intestinal morphophysiology and development early in life. Our findings revealed tachygastria in offspring exposed to MPR. The ultrastructural analysis uncovered a reduction in goblet cell numbers and changes in collagen deposition in the duodenum and colon. We also identified imbalances in inflammatory markers (IL-6 and TGF-β1) and antioxidant enzymes (CAT and SOD). These results demonstrate that MPR significantly affects gastrointestinal morphophysiology early in life by disrupting gastric motility and altering duodenal and colonic histoarchitecture, antioxidant defense, and inflammatory pathways. Such alterations may predispose the descendants to long-term gastrointestinal disorders, underscoring the importance of further research on the developmental origins of intestinal health and disease.

Over the last four decades, clinical research and experimental studies have established that lipopolysaccharide (LPS)-a component of the outer membrane of gram-negative bacteria-is a potent hepatotoxic molecule in humans and animals. Alcohol abuse is commonly associated with LPS endotoxemia. This review highlights LPS molecular structures and modes of release from bacteria, plasma LPS concentrations, induction of microbiota dysbiosis, disruption of gut epithelial barrier, and translocation of LPS into the portal circulation impacting the pathophysiology of hepatic cells via the gut-liver axis. We describe and illustrate the portal vein circulation and its distributaries draining the gastrointestinal tract. We also elaborate on the gut-liver axis coupled with enterohepatic circulation that represents a bidirectional communication between the gut and liver. The review also updates the data on how circulating LPS is cleared in a coordinated effort between Kupffer cells, hepatocytes, and liver sinusoidal endothelial cells. Significantly, the article reviews and updates the modes/mechanisms of action by which LPS mediates the diverse pathophysiology of Kupffer cells, hepatocytes, sinusoidal endothelial cells, and hepatic stellate cells primarily in association with alcohol consumption. Specifically, we review the intricate linkages between ethanol, microbiota dysbiosis, LPS production, gut-liver axis, and pathophysiology of various hepatic cells. The maintenance of the gut barrier structural and functional integrity and microbiome homeostasis is essential in mitigating alcoholic liver disease and improving liver health.

The Highly Pathogenic Island (HPI) found in Yersinia pestis can be horizontally transferred to E. coli, enhancing its virulence and pathogenicity. Ubiquitin (Ub) acts as an activator of the NF-κB pathway and plays a critical role in the inflammatory response. However, the precise mechanism by which Ub and the regulated TLR4/NF-κB pathway contribute to HPI-induced intestinal inflammation in E. coli remains unclear.

In this study, we established Ub overexpression models of small intestinal epithelial cells (in vitro) and BALB/c mice (in vivo) and infected these models with HPI-rich E. coli. We investigated the role of the Ub-regulated TLR4/NF-κB pathway in E. coli HPI-induced intestinal inflammation through qPCR, ELISA, immunofluorescence, immunohistochemistry, and H&E staining. Our findings confirmed that E. coli HPI promoted the expression of Ub, TLR4, and NF-κB in IPEC-J2 cells and induced the translocation of NF-κB p65 protein to the nucleus. Further investigations revealed that Ub overexpression enhanced epithelial cell damage induced by E. coli HPI. This was accompanied by up-regulation of mRNA levels of TLR4, MyD88, NF-κB, IL-1β, and TNF-α, as well as increased release of the inflammatory factors IL-1β and TNF-α. In a mouse model with Ub overexpression infected with E. coli HPI, we observed that Ub overexpression promoted E. coli HPI-induced intestinal inflammation. Mechanistically, E. coli HPI induced intestinal epithelial cell damage by inducing Ub overexpression and modulating the TLR4/NF-κB pathway.

In conclusion, this study sheds light on the significant role of the Ub-regulated TLR4/NF-κB pathway in E. coli HPI-induced duodenitis, offering novel insights into the pathogenesis of E. coli infections.

The present study investigated the role of the neurotensin/NTS in the modulation of the lipopolysaccharide/LPS induced dysfunction of the sympatho-adrenal-medullary system/SAM using both the NTS receptor 1/NTSR1 agonist PD149163/PD and antagonist SR48692 /SR. Forty eight mice were maintained in eight groups; Group I/control, Groups II, III, IV, and VII received LPS for 5 days further Group III/IV/VII received PD low dose/PDL, PD high dose /PDH and SR for 28 days respectively. Group V/VI received similar only PDL and PDH dose respectively whereas Group VIII was exposed to only SR for 28 days. Adrenal tissues histopathology examined through hematoxylin-eosin staining. The plasma levels of pro-inflammatory mediators (NF-kβ, TNF-α, IL-6), IL-10, corticosterone/CORT, nor-epinephrine/NE and NTS were assessed through ELISA. Biochemical detection was adopted to check the level of oxidative stress, assessed by measuring the thiobarbituric acid reactive substance/TBARS, superoxide dismutase/SOD and catalase/CAT in adrenal tissue to determine the therapeutic effect of NTS receptor 1 analogs. Compared with LPS group, PD ameliorated the adrenal medulla histopathology by significantly decreasing pro-inflammatory mediators, CORT and NE as well as enhancing IL-10, normalizing NTS level via down-regulating NF-κβ level. PD inhibited the oxidative stress in SAM system of adrenal by reducing TBARS, while enhancing SOD and CAT activity via regulating the CORT and NE levels. Conversely, SR administration could not normalize the deleterious effect caused by the LPS due to up-regulation of NF-κβ level. Therefore, PD ameliorates the inflammation and oxidative stress of SAM system by inhibiting NF-kβ/NE signaling pathway. Thus, PD could be used as a biological tool in SAM dysfunction for therapeutic evaluation of chronic inflammatory diseases.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major contributor to liver-related morbidity, cardiovascular disease, and metabolic complications. Lifestyle interventions, including diet and exercise, are first line in treating MASLD. Dietary approaches such as the low-glycemic-index Mediterranean diet, the ketogenic diet, intermittent fasting, and high fiber diets have demonstrated potential in addressing the metabolic dysfunction underlying this condition. The development and progression of MASLD are closely associated with taxonomic shifts in gut microbial communities, a relationship well-documented in the literature. Given the importance of diet as a primary treatment for MASLD, it is important to understand how gut microbiota and their metabolic byproducts mediate favorable outcomes induced by healthy dietary patterns. Conversely, microbiota changes conferred by unhealthy dietary patterns such as the Western diet may induce dysbiosis and influence steatotic liver disease through promoting hepatic inflammation, up-regulating lipogenesis, dysregulating bile acid metabolism, increasing insulin resistance, and causing oxidative damage in hepatocytes. Although emerging evidence has identified links between diet, microbiota, and development of MASLD, significant gaps remain in understanding specific microbial roles, metabolite pathways, host interactions, and causal relationships. Therefore, this review aims to provide mechanistic insights into the role of microbiota-mediated processes through the analysis of both healthy and unhealthy dietary patterns and their contribution to MASLD pathophysiology. By better elucidating the interplay between dietary nutrients, microbiota-mediated processes, and the onset and progression of steatotic liver disease, this work aims to identify new opportunities for targeted dietary interventions to treat MASLD efficiently.

High-fat diet (HFD) induces low-grade chronic inflammation, contributing to obesity and insulin resistance. However, the precise mechanisms triggering obesity-associated metabolic inflammation remain elusive. In this study, we identified epigenetic factor Brd4 as a key player in this process by regulating the expression of Ccr2/Ccr5 in colonic macrophage. Upon 4-week HFD, myeloid-lineage-specific Brd4 deletion (Brd4-CKO) mice showed reduced colonic inflammation and macrophage infiltration with decreased expression of Ccr2 and Ccr5. Mechanistically, Brd4 was recruited by NF-κB to the enhancer regions of Ccr2 and Ccr5, promoting enhancer RNA expression, which facilitated Ccr2/Ccr5 expression and macrophage migration. Furthermore, decreased infiltration of Ccr2/Ccr5-positive colonic macrophages in Brd4-CKO mice altered gut microbiota composition and reduced intestinal permeability, thereby lowering metabolic endotoxemia. Finally, Brd4-CKO mice subjected to a 4-week LPS infusion exhibited restored susceptibility to HFD-induced obesity and insulin resistance. This study identifies Brd4 as a critical initiator of colonic macrophage-mediated inflammation and metabolic endotoxemia upon HFD, suggesting Brd4 as a potential target for mitigating HFD-induced inflammation, obesity, and its metabolic complications.

Obstructive sleep apnea (OSA) is a state of sleep disorder, characterized by repetitive episodes of apnea and chronic intermittent hypoxia. OSA has an extremely high prevalence worldwide and represents a serious challenge to public health, yet its severity is frequently underestimated. It is now well established that neurocognitive dysfunction, manifested as deficits in attention, memory, and executive functions, is a common complication observed in patients with OSA, whereas the specific pathogenesis remains poorly understood, despite the likelihood of involvement of inflammation. Here, we provide an overview of the current state of the art, demonstrating the intimacy of OSA with inflammation and cognitive impairment. Subsequently, we present the recent findings on the investigation of gut microbiota alteration in the OSA conditions, based on both patients-based clinical studies and animal models of OSA. We present an insightful discussion on the role of changes in the abundance of specific gut microbial members, including short-chain fatty acid (SCFA)-producers and/or microbes with pathogenic potential, in the pathogenesis of inflammation and further cognitive dysfunction. The transplantation of fecal microbiota from the mouse model of OSA can elicit inflammation and neurobehavioral disorders in naïve mice, thereby validating the causal relationship to inflammation and cognitive abnormality. This work calls for greater attention on OSA and the associated inflammation, which require timely and effective therapy to protect the brain from irreversible damage. This work also suggests that modification of the gut microbiota using prebiotics, probiotics or fecal microbiota transplantation may represent a potential adjuvant therapy for OSA.

The gut microbiota, a diverse collection of microorganisms in the gastrointestinal tract, plays a critical role in regulating metabolic, immune, and cognitive functions. Disruptions in the composition of these microbial communities, termed dysbiosis, have been linked to various neurodegenerative diseases (NDs), such as Parkinson's disease (PD) and Alzheimer's disease (AD). One of the key pathological features of NDs is neuroinflammation, which involves the activation of microglia and peripheral immune cells. The gut microbiota modulates immune responses through the production of metabolites and interactions with immune cells, influencing the inflammatory processes within the central nervous system. This review explores the impact of gut dysbiosis on neuroinflammation, focusing on the roles of microglia, immune cells, and potential therapeutic strategies targeting the gut microbiota to alleviate neuroinflammatory processes in NDs.

The intensive broiler farming model has accelerated the development of the poultry farming industry. However, it has also inevitably brought about many stressors that lead to oxidative stress in the organism. The intestine is the leading site of nutrient digestion, absorption, and metabolism, as well as a secretory and immune organ. Oxidative stress in animal production can harm the intestine, potentially leading to significant losses for the farming industry. Under conditions of oxidative stress, many free radicals are produced in the animal's body, attacking the intestinal mucosal tissues and destroying the barrier integrity of the intestinal tract, leading to disease. Recently, herbs have been shown to have a favorable safety profile and promising application in improving intestinal oxidative stress in poultry. Therefore, future in-depth studies on the specific mechanisms of herbs and their extracts for treating intestinal oxidative stress can provide a theoretical basis for the clinical application of herbs and new therapeutic options for intestinal oxidative stress injury during poultry farming. This review focuses on the causes and hazards of oxidative stress in the intestinal tract of poultry, and on herbs and their extracts with therapeutic potential, to provide a reference for developing and applying new antioxidants.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD)-previously described as nonalcoholic fatty liver disease-continues to rise globally. Despite this, therapeutic measures for MASLD remain limited. Recently, there has been a growing interest in the gut microbiome's role in the pathogenesis of MASLD. Understanding this relationship may allow for the administration of therapeutics that target the gut microbiome and/or its metabolic function to alleviate MASLD development or progression. This review will discuss the interplay between the gut microbiome's structure and function in relation to the development of MASLD, assess the diagnostic yield of gut microbiome-based signatures as a noninvasive tool to identify MASLD severity, and examine current and emerging therapies targeting the gut microbiome-liver axis.

Prostaglandins (PGs) play a crucial role in sleep regulation, yet the broader physiological context that leads to the activation of the prostaglandin-mediated sleep-promoting system remains elusive. In this study, we explored sleep-inducing mechanisms potentially involving PGs, including microbial, immune and thermal stimuli as well as homeostatic sleep responses induced by short-term sleep deprivation using cyclooxygenase-2 knockout (COX-2 KO) mice and their wild-type littermates (WT). Systemic administration of 0.4 µg lipopolysaccharide (LPS) induced increased non-rapid-eye movement sleep (NREMS) and fever in WT animals, these effects were completely absent in COX-2 KO mice. This finding underscores the essential role of COX-2-dependent prostaglandins in mediating sleep and febrile responses to LPS. In contrast, the sleep and fever responses induced by tumor necrosis factor α, a proinflammatory cytokine which activates COX-2, were preserved in COX-2 KO animals, indicating that these effects are independent of COX-2-related signaling. Additionally, we examined the impact of ambient temperature on sleep. The sleep-promoting effects of moderate warm ambient temperature were suppressed in COX-2 KO animals, resulting in significantly reduced NREMS at ambient temperatures of 30 °C and 35 °C compared to WT mice. However, rapid-eye-movement sleep responses to moderately cold or warm temperatures did not differ between the two genotypes. Furthermore, 6 h of sleep deprivation induced rebound increases in sleep with no significant differences observed between COX-2 KO and WT mice. This suggests that while COX-2-derived prostaglandins are crucial for the somnogenic effects of increased ambient temperature, the homeostatic responses to sleep loss are COX-2-independent. Overall, the results highlight the critical role of COX-2-derived prostaglandins as mediators of the sleep-wake and thermoregulatory responses to various physiological challenges, including microbial, immune, and thermal stimuli. These findings emphasize the interconnected regulation of body temperature and sleep, with peripheral mechanisms emerging as key players in these integrative processes.

This study examined the effect of exposure of small and large intestinal epithelial cells to the bacterial lipopolysaccharide (LPS) on uptake of free form of vitamin B1, i.e., thiamin. The intestinal tract encounters two sources of thiamin: diet and the gut microbiota. Absorption of thiamin in both the small and large intestine occurs via a carrier-mediated process that involves thiamin transporters 1 and 2 (THTR-1 and -2). Complementary in vitro (human duodenal epithelial HuTu-80 cells and human colonic epithelial NCM460 cells), in vivo (mice), and ex vivo (human primary differentiated enteroid and colonoid monolayers) models were used. The results showed that exposure to LPS causes a significant inhibition in carrier-mediated [3H]-thiamin uptake by small and large intestinal epithelia, with no change in the levels of expression of THTR-1 and -2 mRNAs and their total cellular proteins. However, a significant decrease in the fractions of the THTR-1 and -2 proteins that are expressed at the cell membranes of these epithelial cells was observed. These effects of LPS appeared to involve a protein kinase A (PKA) signaling pathway as activating this pathway caused a reversal in the inhibition of thiamin uptake and level of expression of its transporters at the cell membrane. These findings demonstrate that exposure of gut epithelia to LPS (a situation that occurs under different pathological conditions) leads to inhibition in thiamin uptake due to a decrease in level of expression of its transporters at the cell membrane that is likely mediated via a PKA signaling pathway. NEW & NOTEWORTHY This study shows that the exposure of gut epithelial cells to bacterial LPS negatively impact the uptake process of the free form of vitamin B1 (i.e., thiamin). This appears to be mediated via suppression in the level of thiamin transporters 1 and 2 (THTR-1 and -2) expression at the cell membrane and involves a protein kinase A (PKA) signaling pathway.

In addition to numerous clinical studies, research using experimental models have contributed extensive evidence to the link between antibiotic exposure and atopic disease. A number of mouse models of allergy have been developed and used to uncover the specific effects of various microbiota members and perturbations on allergy development. Studies in mice that lack microbes entirely have also demonstrated the various components of the immune system that require microbial exposure. The importance of the early-life period and the mechanisms by which atopy "protective" species identified in human cohorts promote immune development have been elucidated in mice. Finally, non-animal models involving human-derived cells shed light on specific effects of bacteria on human epithelial and immune responses. When considered alongside clinical cohort studies, experimental model systems have provided crucial evidence for the link between the neonatal gut microbiota and allergic disease, immensely supporting the stewardship of antibiotic administration in infants. The following review aims to describe the range of experimental models used for studying factors that affect the relationship between the gut microbiota and allergic disease and summarize key findings that have come from research in animal and in vitro models.

Numerous studies have revealed that a long-term high-fat diet can raise intestinal deoxycholate acid concentration, which can harm intestinal mucosal barrier function in several ways. This study aims to verify the protective effect of GYY4137, as a slow-releasing H2S donor, on microbiome disturbance and the chronic injury of the intestinal mucosal barrier function caused by sodium deoxycholate.

Caco-2 monolayer and mouse models were treated with a relatively high concentration of sodium deoxycholate (1.0 mM and 0.2%, respectively) for longer periods (32 h and 12 weeks, respectively) to understand the effects of GYY4137 on sodium deoxycholate-induced chronic intestinal barrier dysfunction and its fundamental mechanisms.

A relatively long period of sodium deoxycholate treatment can remarkably increase the intestinal barrier permeability, alter the distribution and expression of tight junction proteins and generate the production of pro-inflammatory cytokines (TNF-α and IL-1β) in the Caco-2 monolayers and mouse models. Moreover, it can activate the MLCK-P-MLC2 pathway in the Caco-2 monolayers, which was further confirmed using RNA sequencing. The body weight, intestinal barrier histological score, and TUNEL index of sodium deoxycholate-treated mice worsened. In addition, an induced microbiome imbalance was observed in these mice. The above variations can be reversed with the administration of GYY4137.

This study demonstrates that GYY4137 ameliorates sodium deoxycholate-induced chronic intestinal barrier injury by restricting the MLCK-P-MLC2 pathway while elevating the expression level of tight junction proteins, anti-apoptosis and maintaining the microbiome's homeostasis.

Developmental stuttering is a complex neurodevelopmental disorder characterized by disfluent speech. It has been associated with mutations in genes involved in lysosomal enzyme trafficking. Mice with mutations in one such gene, Gnptab, exhibit atypical vocalizations analogous to stuttering in humans. This mouse model has enabled the study of various molecular mechanisms related to the disorder. Simultaneously, an increasing number of reports have suggested the role of gut microbiota in altered brain function and development in neurological disorders. In this study, we compared gut microbiota profiles from Gnptab mutant mice to wildtype control mice. Microbiome analysis demonstrated a distinct microbiota profile in Gnptab mutant mice. The most significant alteration was an increased relative abundance of Akkermansia, a genus of mucin degrading bacteria, which has previously been associated with multiple neurological disorders. Moreover, the altered microbiota profile of these mice was predicted to result in differences in abundance of several metabolic pathways, including short chain fatty acid and lipopolysaccharide synthesis. These pathways may play a role in the onset, progression and persistence of developmental stuttering. This is the first study to show a potential link between developmental stuttering and changes in the gut microbiota, laying the groundwork for a new research direction.

To study the para- and transcellular permeability of columnar epithelium and follicle-associated epithelium of Peyer's patches in the rat intestine, LPS was applied from the mucosal side to simulate the action of endotoxins from gram-negative bacteria of gut microbiota. LPS did not affect transepithelial resistance or sodium fluorescein permeability, but increased the levels of claudin-3 and claudin-4 in enterocytes, suggesting strengthening of the paracellular intestinal barrier. Transcellular permeability was evaluated by electron microscopy based on the number of vesicular structures in the cytoplasm of different cell types. LPS increased the number of small vesicles in follicle-associated epithelium of Peyers' patches. In columnar epithelial cells, LPS reduced the number of smaller vesicles and increased the number of larger ones. LPS did not damage the tissue barrier, but enhanced transcytosis, which could potentiate the effects of endotoxin on its receptors in the intestinal mucosa.

Microbial interactions are widespread and important processes that support the link between disease and microbial ecology. The gut microbiota is a major source of microbial stimuli that can have detrimental or beneficial effects on human health. It is also an endocrine organ that maintains energy homeostasis and host immunity. Obesity is a highly and increasingly prevalent metabolic disease and the leading cause of preventable death worldwide. An imbalance in the gut microbiome is associated with several diseases including obesity-related metabolic disorders. This review summarizes the complex association between the gut microbiome and obesity-associated metabolic diseases and validates the role and mechanisms of ecological dysregulation in the gut in obesity-associated metabolic disorders. Therapies that could potentially alleviate obesity-associated metabolic diseases by modulating the gut microbiota are discussed.

Epidemiological studies have revealed an inverse relationship between the incidence of Alzheimer's disease (AD) and various cancers, including colorectal cancer (CRC). We aimed to determine whether the incidence of CRC is reduced in AD-like mice and whether gut microbiota confers resistance to tumorigenesis through inducing inflammatory tolerance using 16S ribosomal RNA gene sequencing and fecal microbiota transplantation (FMT). AD-like mice experienced a significantly decreased incidence of CRC tumorigenesis induced by azoxymethane-dextran sodium sulfate as evidenced by suppressed intestinal inflammation compared with control mice. However, FMT from age-matched control mice reversed the inhibitory effects on the tumorigenesis of CRC and inflammatory response in AD-like mice. The key bacterial genera in gut microbiota, including Prevotella, were increased in both the AD-like mice and in patients with amnestic mild cognitive impairment (aMCI) but were decreased in patients with CRC. Pretreatment with low-dose Prevotella-derived lipopolysaccharides (LPS) induced inflammatory tolerance both in vivo and in vitro and inhibited CRC tumorigenesis in mice. Imbalanced gut microbiota increased intestinal barrier permeability, which facilitated LPS absorption from the gut into the blood, causing cognitive decline in AD-like mice and patients with aMCI. These data reveal that intestinal Prevotella-derived LPS exerts a resistant effect to CRC tumorigenesis via inducing inflammatory tolerance in the presence of AD. These findings provide biological evidence demonstrating the inverse relationship between the incidence of AD and CRC.