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The toxic effects of tire wear particles (TWPs) in the environment are a growing concern for a variety of aquatic organisms. However, studies about TWPs toxicity on aquatic organisms are limited. This study investigated the accumulation and depuration of TWPs in zebrafish at three different concentrations (5 mg/L, 10 mg/L, and 20 mg/L), as well as the toxic effects on the gill, liver, and gut. We found that TWPs could accumulate in the gill and gut for a long time, and the number of TWPs at the high-concentration (20 mg/L) was higher than at the low-concentration (5 mg/L). TWPs induced oxidative stress in the gill and liver. The liver transcriptome profiles indicated that the high concentration of TWPs tended to up-regulate metabolic processes, whereas the low concentration of TWPs was inclined to down-regulate cellular processes. The high-concentration treatment significantly increased xenobiotic biodegradation and metabolism, and lipid metabolism-related pathways, whereas the low-concentration treatment distinctly altered amino acid metabolism-related pathways. The expression of gstt1b, ugt1a1, mgst3b, miox, hsd17b3, and cyp8b1 gene was up-regulated in all TWPs treatments. In addition, Gemmobacter and Shinella enriched in the high-concentration treatment were closely correlated with the degradation of TWPs. These findings provided objective evidence for the toxicity evaluation of TWPs on zebrafish., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Spodoptera frugiperda is an economic agricultural pest that has invaded many countries around the world and caused huge losses in grain production. Camptothecin (CPT) is one of the botanical compounds with insecticidal activity and has the potential for pest control. However, the effects of CPT on development and metabolism of S. frugiperda remain unknown. In this study, we have investigated the adverse effects of 1.0 and 5.0 mg/kg CPT exposures on the growth and development of S. frugiperda. Our results found that 1.0 and 5.0 mg/kg CPT treatments altered the parameters of the life cycle, including inducing larval mortality, altering the weight of larvae, pupae, and adults, the larval duration, and decreasing the pupation rate and emergence rate. In addition, comparative metabolomics analysis was performed in the larval midgut of S. frugiperda to explore the toxicity mechanism of CPT. A total of 261 and 348 differential metabolites were identified in the groups with 1.0 and 5.0 mg/kg CPT treatments, respectively. Further analysis found that pantothenate and CoA biosynthesis, sulfur relay system, selenocompound metabolism, and fatty acid biosynthesis pathways were significantly altered by 5.0 mg/kg CPT exposure. Our results provided new insight into the toxicological mechanisms of CPT against S. frugiperda and laid the foundation for the field application of CPT in pest control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Erythrosine, a synthetic food dye, has been controversial due to its potential health risks. This study examines the effect of erythrosine on activity of antioxidative enzymes, oxidative stress indices, DNA damage through comet assay, and histopathological changes on stomach, intestine, and colon over a period of 28 days in rats. Twenty-four rats were randomly divided into four groups (n = 6). The first is the control group and then one each for three doses of erythrosine based on acceptable daily intake (¼ ADI, ½ ADI, and ADI, 0.1 mg/kg body weight). The results revealed that with increasing dosages the activity of catalase decreased in stomach and intestine but in colon, the catalase activity increased. Superoxide dismutase and glutathione-S-transferase activity decreased in dose-dependent manner in all three tissues. While, in stomach and intestine, the acetylcholinesterase activity showed increment in ¼ ADI dose group and then declined in ½ ADI and ADI dose-administered rats. The oxidative stress indicators showed elevated levels of lipid peroxidation, hydrogen peroxide concentration, and lactate dehydrogenase activity suggesting heightened free radical activity and potential oxidative damage. The comet test was used to evaluate DNA damage, revealing substantial damage in the erythrosine administered groups. Histopathological examination showed inflammatory infiltration and other degenerative changes in gastrointestinal tract, highlighting the dye's adverse effects. The research underscores the need for a comprehensive reevaluation of the safety and toxicity of food dyes like erythrosine, especially considering the inconsistencies in existing studies regarding the dye's safety., (© 2024 Wiley Periodicals LLC.)

An experiment was conducted to assess the response of chicks to in-ovo injection of Bacillus subtilis (probiotic), raffinose (prebiotic), and their combinations. The study used 1,500 embryonated eggs allotted to 10 groups/ 6 replicates (150 eggs/group). The experimental treatments were: 1) un-injected control (NC); 2) sham (sterile distilled water) (PC); 3) probiotic 4 × 10 5 CFU/egg (LBS); 4) probiotic 4 × 10 6 CFU/egg (HBS); 5) prebiotic 2 mg/egg (LR); (6 prebiotic 3 mg/egg (HR); 7) probiotic 4 × 10 5 CFU + prebiotic 2 mg/egg (LBS+LR); 8) probiotic 4 × 10 5 CFU + prebiotic 3 mg/egg (LBS+HR); 9) probiotic 4 × 10 6 CFU + prebiotic 2 mg/egg (HBS+LR); and 10) probiotic 4 × 10 6 CFU + prebiotic 3 mg/egg (HBS+HR). Results showed that in-ovo inclusion of Bacillus subtilis, prebiotic, and their combinations improved hatchability, yolk-free chick weight, and chick weight compared to the control group. Moreover, the in-ovo treatment reduced residual yolk weight on the day of hatch compared to the control group. Different levels of in-ovo B. subtilis alone or combined with raffinose significantly (P ≤ 0.001) reduced total bacterial count and total yeast and mold count compared to the negative control group. Total coliform and E. coli decreased significantly (P ≤ 0.001) in groups treated with probiotics, prebiotics, and synbiotics with different doses during incubation compared to those in the control. Clostridium spp. was not detected in the groups injected with B. subtilis alone or combined with raffinose. In-ovo probiotics and synbiotics (LBS+LR & LBS+HR) significantly (P ≤ 0.001) increased ileal villus length compared to other groups. In-ovo treatment increased mRNA expression of JAM-2 compared to the control group. The fold change significantly increased in group LBS+HR for genes MUC-2, OCLN, VEGF, SGLT-1, and EAAT-3 compared to the negative control. In conclusion, in-ovo injection of a low dose of B. subtilis plus a high or low dose of raffinose can positively affect hatching traits, cecal microbial populations, intestinal histomorphometry, nutrient transport- and intestinal function-related genes, and chick quality of newly hatched broiler chicks., Competing Interests: DISCLOSURES The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Metformin, the first line treatment for patients with type 2 diabetes mellitus, has alternative novel roles, including cancer and diabetes prevention. This narrative review aims to explore its diverse mechanisms, effects and intolerance, using sources obtained by searching Scopus, PubMed and Web of Science databases, and following Scale for the Assessment of Narrative Review Articles reporting guidelines. Metformin exerts it actions through duration influenced, and organ specific, diverse mechanisms. Its use is associated with inhibition of hepatic gluconeogenesis targeted by mitochondria and lysosomes, reduction of cholesterol levels involving brown adipose tissue, weight reduction influenced by growth differentiation factor 15 and novel commensal bacteria, in addition to counteraction of meta-inflammation alongside immuno-modulation. Interactions with the gastrointestinal tract include alteration of gut microbiota, enhancement of glucose uptake and glucagon like peptide 1 and reduction of bile acid absorption. Though beneficial, they may be linked to intolerance. Metformin related gastrointestinal adverse effects are associated with dose escalation, immediate release formulations, gut microbiota alteration, epigenetic predisposition, inhibition of organic cation transporters in addition to interactions with serotonin, histamine and the enterohepatic circulation. Potentially effective measures to overcome intolerance encompasses carefully objective targeted dose escalation, prescription of fixed dose combination, microbiome modulators and prebiotics, in addition to use of extended release formulations., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Aquaculture, traditionally a form of biotechnology, has evolved to integrate innovative biotechnological applications, such as advanced feed formulations, aimed at improving the growth performance and health of farmed fish species. In the present study, the effects of feeding rainbow trout with novel feed formulations were investigated. Fish growth, gut and liver morphology, the concentration of fatty acids in the fillet, and volatile fatty acids in the gut were assessed. The study also validated scenarios from in vivo experiments using a nutrient-based model called FEEDNETICS™. This globally used model serves as a tool for data interpretation and decision support in the context of precision fish farming., Methods: Alternative protein and oil sources, including poultry by-product meal (PBM) and natural algae oil, were explored as sustainable replacements for fishmeal (FM) and fish oil (FO). A 90-day feeding trial was conducted using rainbow trout, comparing two isoproteic, isolipidic and isoenergetic diets. The control diet contained 15% FM, 5% PBM, and 8% FO, while the test diet replaced FM with 15% PBM and 5% feather meal hydrolysate (FMH), and fully substituted FO with VeraMaris ® natural algae oil and rapeseed oil., Results: PBM successfully replaced FM protein without negatively affecting feed intake, growth performance or feed utilization in trout. The combination of PBM and natural algae oil was well tolerated by the trout and showed no negative effects on gut health. A detailed analysis of fatty acids in the fillet revealed that PUFAs of the n3 and n6 series were significantly higher in the PBM group than in the FM group. Values of fatty acid-related health indexes, including atherogenicity index, and thrombogenicity index, confirmed the high nutritional value of trout filet, thus representing a healthy product for human. In addition, the predictions using the FEEDNETICS™ indicated that the tested novel alternative formulations are economically viable. The validation of the model for fish growth resulted in a Mean Absolute Percentage Error (MAPE) of 8%., Conclusions: The FEEDNETICS™ application enhances our ability to optimize feeding strategies and improve production efficiency in the aquaculture industry. VeraMaris ® algae oil and PBM could serve as viable and sustainable raw materials for fish feed, promoting environmentally friendly aquaculture practices., (© 2024. The Author(s).)

The gastrointestinal tract's epithelial barrier plays a crucial role in maintaining health. This study aims to investigate the impact of glutamine supplementation on intestinal permeability, considering its importance for immune function and nutrient absorption. The study adhered to the PRISMA protocol for systematic reviews and meta-analyses. A systematic search was performed in four databases (PubMed, Scopus, Web of Science, and Google Scholar) until April 2023 to identify clinical trials on glutamine supplementation and gastrointestinal permeability. Eligibility criteria included randomized placebo-controlled trials measuring gut permeability post-glutamine supplementation. Studies were included regardless of language or publication date. Data extraction involved study characteristics, intervention details, and outcomes. Quality assessment was performed using the Cochrane tool, and statistical analysis utilized mean differences and standard deviations with a random effects model. Subgroup analysis was conducted to explore heterogeneity. The systematic review and meta-analysis included 10 studies from 1998 to 2014 with 352 participants. A total of 216 patients were enrolled in the intervention group, and 212 in the control group. The mean participant age was 46.52 years. The participants had different types of diseases in terms of their health status. Overall, glutamine supplementation did not significantly affect intestinal permeability (WMD: -0.00, 95% CI -0.04, 0.03). Subgroup analysis showed a significant reduction in intestinal permeability with doses over 30g/day (WMD: -0.01, 95% CI -0.10, -0.08). The glutamine supplements were administered orally in all included studies. The meta-analysis demonstrated a significant reduction in intestinal permeability with glutamine supplementation exceeding 30 mg/day for durations of less than 2 weeks. Further investigations with varying dosages and patient populations are warranted to enhance understanding and recommendations regarding glutamine supplementation's effects on gut permeability., (© 2024. The Author(s).)

Although irregularly-shaped label-free microplastics (MPs) are predominantly distributed in the environment, non-destructive analysis of environmentally relevant MPs in organisms is still challenging. The purpose of the study is to suggest in vivo visual evidence of the uptake and effect of environmentally relevant MPs in organism. Transparent irregularly-shaped high-density polyethylene was selected as an environmentally relevant model MP and exposed to brine shrimp (Artemia franciscana). As a result, we suggest the application of SEM/EDX and coherent anti-Stokes Raman scattering (CARS) microspectroscopy as complementary tools to secure in vivo visual evidence of irregularly-shaped unlabeled MPs in living organisms without chemical digestion for biodistribution observations. Biological transmission electron microscopy also provides how ingested MPs physically affects the digestive tract in the brine shrimp which is rarely reported. In terms of environmental implications, this study would advance ecotoxicological research on microplastic pollution by providing a cutting-edge tool for investigating the bioavailability and ecotoxicity of environmentally relevant MPs in ecosystems., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Total-body irradiation (TBI) with gamma rays can damage organisms in various unexpected ways and trigger several organ dysfunction syndromes, such as acute radiation syndrome (ARS). Hematopoietic cells and enterocytes are particularly sensitive to radiation due to their self-renewal ability and rapid division, which leads to hematopoietic ARS (H-ARS) and gastrointestinal ARS (GI-ARS). We previously showed that a lipid-based small molecule, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG), improved 30-day survival and alleviated H-ARS symptoms in BALB/c mice after a lethal dose (LD70/30) of gamma-ray TBI. In this study, we investigated the mitigating effects of PLAG on radiation-induced GI damage that occurs under the same conditions as H-ARS in BALB/c mice. Our study showed that PLAG facilitated the structural restoration of intestinal tissues by increasing villus height, crypt depth, crypt number, mucin-producing goblet cells, and proliferating cell nuclear antigen (PCNA)-positive crypt cells. PLAG significantly improved intestinal absorptive capacity and reduced intestinal injury-induced bacterial translocation. In addition, PLAG effectively inhibited radiation-induced necroptosis signaling activation in the intestinal crypt cells, which was responsible for sustained tissue damage and the release of high mobility group box 1 (HMGB1), a typical damage-associated molecular pattern. Overall, our findings support the radiation-mitigating potential of PLAG against GI-ARS after accidental radiation exposure., (© 2024 by Radiation Research Society. All rights of reproduction in any form reserved.)

Since the early 1990s, when Robert's and Szabo's cytoprotection concept had already been more than one decade old, but still not implemented in therapy, we suggest the stable gastric pentadecapeptide BPC 157 as the most relevant mediator of the cytoprotection concept. Consequently, it can translate stomach and gastrointestinal mucosal maintenance, epithelium, and endothelium cell protection to the therapy of other tissue healing (organoprotection), easily applicable, as native and stable in human gastric juice for more than 24 h. These overwhelm current clinical evidence (i.e., ulcerative colitis, phase II, no side effects, and no lethal dose (LD1) in toxicology studies), as BPC 157 therapy effectively combined various tissue healing and lesions counteraction. BPC 157 cytoprotection relevance and vascular recovery, activation of collateral pathways, membrane stabilizer, eye therapy, wound healing capability, brain-gut and gut-brain functioning, tumor cachexia counteraction, muscle, tendon, ligament, and bone disturbances counteraction, and the heart disturbances, myocardial infarction, heart failure, pulmonary hypertension, arrhythmias, and thrombosis counteraction appeared in the recent reviews. Here, as concept resolution, we review the counteraction of advanced Virchow triad circumstances by activation of the collateral rescuing pathways, depending on injury, activated azygos vein direct blood flow delivery, to counteract occlusion/occlusion-like syndromes starting with the context of alcohol-stomach lesions. Counteraction of major vessel failure (congested inferior caval vein and superior mesenteric vein, collapsed azygos vein, collapsed abdominal aorta) includes counteraction of the brain (intracerebral and intraventricular hemorrhage), heart (congestion, severe arrhythmias), lung (hemorrhage), and congestion and lesions in the liver, kidney, and gastrointestinal tract, intracranial (superior sagittal sinus), portal and caval hypertension, aortal hypotension, and thrombosis, peripherally and centrally., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Concerns about microplastic (MP) pollution in terrestrial systems are increasing. It is believed that the overall amount of MPs in the terrestrial system could be 4-23 times higher than that in the ocean. Agricultural ecosystems are among the most polluted areas with MPs. Terrestrial organisms such as ground beetles, will be more vulnerable to MPs in various agricultural soil types because they are common in garden and agricultural areas. Therefore, this work aims to assess for the first time the potential adverse effects of chronic exposure for 30 days of ground beetles to a field-realistic concentration of 2 % (w/w) of three different irregularly shaped MPs polymers: Polystyrene (PS), polyethylene terephthalate (PET), and polyamide 6 (PA; i.e., nylon 6) on their health. The results showed no effect on beetle survival; nevertheless, there was a decrease in beetle defecation rate, particularly in beetles exposed to PS-MPs, and a change in the activity of midgut digestive enzymes. The effects on digestive enzymes (amylase, protease, lipase, and α-glucosidase) were polymer and enzyme specific. Furthermore, histological and cytological studies demonstrated the decomposition of the midgut peritrophic membrane, as well as abnormally shaped nuclei, vacuolation, disordered microvilli, necrosis of goblet and columnar cells, and necrosis of mitochondria in midgut cells. Given the importance of ground beetles as predators in most agricultural and garden settings, the reported adverse impacts of MPs on their health may impact their existence and ecological functions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The objective of the present study was to compare the effectiveness of dietary supplementation of muramidase (MUR) and 2 phytogenic additives on the growth performance, intestinal morphology, bacteria load, and production of short-chain fatty acids (SCFA) of broiler chickens raised under field-like conditions. A total of 6,400 day-old Ross 308 broiler chicks were randomly selected and distributed into 32 floor pens, with 200 chicks (100 males and 100 females)/pen. The treatment groups were an unsupplemented control, and the experimental groups supplemented with MUR at 35,000 LSU(F)/kg of feed, phytogenic 1 (Phyto 1, based on thymol) at 100g/ton feed, or phytogenic 2 (Phyto 2, based on alkaloids) at 60g/ton feed, for a total period of 41 d. A 4-phase feeding program was applied (starter, grower, finisher and withdrawal). The paramenters evaluated were: growth performance, carcass yield, concentration of muranic acid in the jejunum content and excreta, liver enzyme concentration, intestinal morphology, and bacteria enumeration and short and branch chain fatty acids (SCFA and BCFA) in the cecal content. Data were analyzed by ANOVA and Tukey's test was used to separate the means. Soluble muramic acid (MurN) in the jejunum increased with the supplementation of MUR and Phyto 2 when compared to the other groups (P = 0.0001), but only the supplementation of MUR increased the concentration of MurN in the excreta. The supplementation of all feed additives improved the body weight gain and the body weight corrected feed conversion ratio when compared to the control group (P = 0.0001). MUR increased villus heigh (VH) when compared to the control or the other supplemented groups (P = 0.0001), and led to the highest concentration of most SCFA, total BCFA, and total SCFA (P < 0.05). In conclusion, the supplementation of MUR and phytogenics to the diets of broiler chickens improved the growth performance, but MUR, only, was capable of effectively degrading peptidoglycans (PGNs) in both intestinal segments, as well as to increase the abundance of beneficial bacteria and SCFA production., Competing Interests: DISCLOSURES CB, EPC, OG are employed by dsm-firmenich. The other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Opioid receptors are found throughout the gastrointestinal tract, including the large intestine. Many patients treated with opioids experience opioid-induced constipation (OIC). Laxatives are not effective in most patients, and in those who do initially respond, the efficacy of laxatives generally diminishes over time. In addition, OIC does not spontaneously resolve for most patients. However, complications of opioids extend far beyond simply slowing gastrointestinal transit. Opioid use can affect intestinal permeability through a variety of mechanisms. Toll-like receptors are a crucial component of innate immunity and are tightly regulated within the gut epithelium. Pathologic µ-opioid receptor (MOR) and toll-like receptor signaling, resulting from chronic opioid exposure, disrupts intestinal permeability leading to potentially harmful bacterial translocation, elevated levels of bacterial toxins, immune activation, and increased cytokine production. Peripherally active MOR antagonists, including methylnaltrexone, are effective at treating OIC. Benefits extend beyond simply blocking the MOR; these agents also act to ameliorate opioid-induced disrupted intestinal permeability. In this review, we briefly describe the physiology of the gastrointestinal epithelial border and discuss the impact of opioids on gastrointestinal function. Finally, we consider the use of peripherally active MOR antagonists to treat disrupted intestinal permeability resulting from opioid use and discuss the potential for improved morbidity and mortality in patients treated with methylnaltrexone for opioid-induced bowel disorders., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Microplastics in food and drinking water can enter the human body through oral exposure, posing potential health risks to the human health. Most studies on the toxic effects of microplastics have focused on aquatic organisms, but the effects of the human digestive environment on the physicochemical properties of microplastics and their potential toxicity during gastrointestinal digestion are often limited. In this study, we first studied the influence of interactions between digestive tract protein (α-amylase, pepsin, and trypsin) and microplastics on the activity and conformation of digestive enzymes, and the physicochemical properties of polyvinyl chloride microplastics (PVC-MPs). Subsequently, a simulated digestion assay was performed to determine the biotransformation of PVC-MPs in the digestive tract and the intestinal toxicity of PVC-MPs. The in vitro experiments showed that the protein structure and activity of digestive enzymes were changed after adsorption by microplastics. After digestion, the static contact angle of PVC-MPs was decreased, indicating that the hydrophilicity of the PVC-MPs increased, which will increase its mobility in organisms. Cell experiment showed that the altered physicochemical property of PVC-MPs after digestion process also affect its cytotoxicity, including cellular uptake, cell viability, cell membrane integrity, reactive oxygen species levels, and mitochondrial membrane potential. Transcriptome analyses further confirmed the enhanced biotoxic effect of PVC-MPs after digestion treatment. Therefore, the ecological risk of microplastics may be underestimated owing to the interactions of microplastics and digestive tract protein during biological ingestion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: A GPCR (G protein-coupled receptor) target-based approach was applied to identify antagonists of the arthropod-specific tick kinin receptor. These small molecules were expected to reproduce the detrimental phenotypic effects that had been observed in Rhipicephalus microplus females when the kinin receptor was silenced by RNA interference. Rhipicephalus microplus, the southern cattle tick, cattle fever tick, or Asian blue tick, is the vector of pathogenic microorganisms causing the deadly bovine babesiosis and anaplasmosis. The widespread resistance to acaricides in tick populations worldwide emphasizes that exploring novel targets for effective tick control is imperative., Results: Fifty-three structural analogs of previously identified tick kinin antagonists were screened in a 'dual-addition' calcium fluorescence assay using a CHO-K1 cell line expressing the tick kinin receptor. Seven molecules were validated as non-cytotoxic antagonists, four of which were partial (SACC-0428764, SACC-0428780, SACC-0428800, and SACC-0428803), and three were full antagonists (SACC-0428799, SACC-0428801, and SACC-0428815). Four of these antagonists (SACC-0428764, SACC-0428780, SACC-0428799, and SACC-0428815) also inhibited the tick midgut contractions induced by the myotropic kinin agonist analog 1728, verifying their antagonistic bioactivity. The small molecules were tested on recombinant human neurokinin (NK) receptors, the one most similar to the invertebrate kinin receptors. Most molecules were inhibitors of the NK1 receptor, except SACC-0412066, a previously identified tick kinin receptor antagonist, which inhibited the NK1 receptor only at the highest concentration tested (25 μm). None of the molecules inhibited the NK3 human receptor., Conclusion: Molecules identified through this approach could be useful probes for studying the tick kinin signaling system and midgut physiology. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Cannabidiol (CBD) is a major non-psychotropic phytocannabinoid that exists in the Cannabis sativa plant. CBD has been found to act on various receptors, including both cannabinoid and non-cannabinoid receptors. In addition, CBD has antioxidant effects that are independent of receptors. CBD has demonstrated modulatory effects at different organ systems, such as the central nervous system, immune system, and the gastrointestinal system. Due to its broad effects within the body and its safety profile, CBD has become a topic of therapeutic interest. This literature review summarizes previous research findings with regard to the effect of CBD on the gastrointestinal (GI) system, including its effects at the molecular, cellular, organ, and whole-body levels. Both pre-clinical animal studies and human clinical trials are reviewed. The results of the studies included in this literature review suggest that CBD has significant impact on intestinal permeability, the microbiome, immune cells and cytokines. As a result, CBD has been shown to have therapeutic potential for GI disorders such as inflammatory bowel disease (IBD). Furthermore, through interactions with the gut, CBD may also be helpful in the treatment of disorders outside the GI system, such as non-alcoholic liver disease, postmenopausal disorders, epilepsy, and multiple sclerosis. In the future, more mechanistic studies are warranted to elucidate the detailed mechanisms of action of CBD in the gut. In addition, more well-designed clinical trials are needed to explore the full therapeutic potential of CBD on and through the gut.

Exposure to arsenic (As) induces adverse effects on human health. Vitamins B1, B6, and C, as indispensable micronutrients for humans, have been proven to influence the metabolism and toxicity of ingested As. To determine the effect of vitamins on health risks associated with soil exposure, As bioaccessibility in 14 soil samples using four in vitro methods of IVG, PBET, SBRC, and UBM was measured with the addition of vitamins B1, B6, and C. With vitamins B1 and B6 addition, the gastric As bioaccessibility in 14 soil samples was reduced by 1.14-3.52 and 1.14-5.02 fold, respectively, and instead an increase in the intestinal bioaccessibility was presented in some cases. Vitamin C supplementation yielded higher As bioaccessibility in the gastric (1.13-13.02 fold) and small intestinal (1.21-33.35 fold) phases, respectively. As evidenced by the X-ray absorption near-edge spectroscopy (XANES) and Fourier transform infrared spectroscopy (FTIR) analysis, arsenic dissolution was promoted by Fe-As and hindered by the formation of Al-As fractions. Soil As dissolution in the simulated gastrointestinal tract was strongly influenced by soil minerals and ingested vitamins, due to the chelation of arsenic with vitamins and soil minerals such as Fe (hydr)oxides, and Fe(III) reductive dissolution to enhance As release by vitamin C as an iron reducer. These findings will expand the knowledge of health risks of exposure to As-contaminated soils and nutritional interventions aiming at the mitigation of As toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Chemotherapy is associated with the induction of intestinal microbiota dysbiosis and gastrointestinal injuries. In this Cell Host & Microbe issue, Anderson et al. demonstrate that chemotherapy-induced epithelial cell apoptosis drives microbiota imbalance and transcriptional rewiring, which in turn delays intestinal recovery., Competing Interests: Declaration of interests H.G. holds equity shares in GoldCrest Bio. H.G. is named as an inventor of US Provisional Patent Application Serial No. 62/779,776 entitled “Lachnospiraceae mitigates against radiation-induced hematopoietic/gastrointestinal injury and death, and promotes cancer control by radiation.”, (Copyright © 2024 Elsevier Inc. All rights reserved.)

Diaphorina citri is a serious citrus pest. Dinotefuran is highly insecticidal against D. citri . To analyze the sublethal effects of dinotefuran on D. citri adults, an indoor toxicity test was performed, which revealed that the lethal concentration 50 (LC 50 ) values were 4.23 and 0.50 μg/mL for 24 and 48 h treatments, respectively. RNA-Seq led to the identification of 71 and 231 differentially expressed genes (DEGs) after dinotefuran treatments with LC 20 and LC 50 doses, respectively. Many of the DEGs are significantly enriched in the apoptosis pathway. Dinotefuran-induced apoptosis in the gut cells was confirmed through independent assays of 4',6-diamidino-2-phenylindole (DAPI) and TdT-mediated dUTP nick end labeling (TUNEL) staining. Increased levels of reactive oxygen species (ROS) and a loss of mitochondrial membrane potential were observed. Four caspase genes were identified, and dinotefuran treatments resulted in increased mRNA levels of DcCasp1 and DcCasp3a . These findings shed light on the sublethal effects of dinotefuran on D. citri .

Poor air quality is increasingly linked to gastrointestinal diseases, suggesting a potential correlation with human intestine health. However, this relationship remains largely unexplored due to limited research. This study used a controlled mouse model exposed to cooking oil fumes (COFs) and metagenomics, transcriptomics, and metabolomics to elucidate interactions between intestine microbiota and host metabolism under environmental stress. Our findings reveal that short-term COF inhalation induces pulmonary inflammation within 3 days and leads to gastrointestinal disturbances, elucidating a pathway connecting respiratory exposure to intestinal dysfunction. The exposure intensity significantly correlates with changes in intestinal tissue integrity, microbial composition, and metabolic function. Extended exposure of 7 days disrupts intestine microbiota and alters tryptophan metabolism, with further changes observed after 14 days, highlighting an adaptive response. These results highlight the vulnerability of intestinal health to airborne pollutants and suggest a pathway through which inhaled pollutants may affect distant organ systems.

This study aimed to investigate the effects of dietary Bacillus velezensis KNF-209 (BV-KNF-209) on the growth performance, immunity, and gut health of broilers. A total of 540 one-day-old male Cobb-500 broilers were randomly divided into 5 groups of 6 replicates with 18 broilers per replicate. Dietary treatments were corn-soybean meal basal diets supplemented with 0, 50, 100, 200, and 400 mg/kg BV-KNF-209 (CON, BV 50, BV 100, BV 200, and BV 400 groups, respectively) for 42 d. Compared with the CON group, the average daily gains (ADG) at 0 to 42 d in the BV 100 and BV 200 groups were significantly increased (P < 0.01), and the feed-to-gain (F:G) ratios were significantly decreased at 0 to 21 d (P < 0.01) and 0 to 42 d (P < 0.05). The BV 200 and BV 400 groups had higher serum immunoglobulin M (IgM) levels at d 21 and 42 (P < 0.05). The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) were significantly decreased in the BV 50, BV 100, and BV 200 groups at d 21 (P < 0.05), and serum IL-1β and IL-6 levels were also reduced in the BV 100 and BV 200 groups at d 42 (P < 0.05). Meanwhile, increased interleukin-10 (IL-10) levels in the jejunal and ileal mucosa at d 42 were observed in the BV 100, BV 200, and BV 400 groups (P < 0.05), while the IL-1β and IL-6 levels (P < 0.01) were decreased. The BV 200 and BV 400 groups showed significantly higher activities of lipase and trypsin (P < 0.05) in jejunal digesta as well as higher activities of amylase and trypsin (P < 0.01) in ileal digesta at d 42. The cecal acetic acid and propionic acid levels in the BV groups and lactic acid levels in the BV 50, BV 100, and BV 200 groups (P < 0.05) were significantly higher compared to those in the CON group. Overall, dietary BV-KNF-209 supplementation significantly improved broiler growth performance, an effect that may have been achieved by heightening immunity, increasing digestive enzyme activity, and raising intestinal short-chain fatty acids and lactic acid levels., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Inc.)

The gastrointestinal tract (GIT) is an important and complex system by which humans to digest food and absorb nutrients. The GIT is vulnerable to diseases, which may led to discomfort or even death in humans. Therapeutics for GIT disease treatment face multiple biological barriers, which significantly decrease the efficacy of therapeutics. Recognizing the biological barriers and pathophysiological characteristics of GIT may be helpful to design innovative therapeutics. Nanotherapeutics, which have special targeting and controlled therapeutic release profiles, have been widely used for the treatment of GIT diseases. Herein, we provide a comprehensive review of the biological barrier and pathophysiological characteristics of GIT, which may aid in the design of promising nanotherapeutics for GIT disease treatment. Furthermore, several typical diseases of the upper and lower digestive tracts, such as Helicobacter pylori infection and inflammatory bowel disease, were selected to investigate the application of nanotherapeutics for GIT disease treatment.

An emerging concern globally, particularly in developed countries, is the rising prevalence of Inflammatory Bowel Disease (IBD), such as Crohn's disease. Oral delivery technologies that can release the active therapeutic cargo specifically at selected sites of inflammation offer great promise to maximise treatment outcomes and minimise off-target effects. Therapeutic strategies for IBD have expanded in recent years, with an increasing focus on biologic and nucleic acid-based therapies. Reliable site-specific delivery in the gastrointestinal (GI) tract is particularly crucial for these therapeutics to ensure sufficient concentrations in the targeted cells. Ingestible smart capsules hold great potential for precise drug delivery. Despite previous unsuccessful endeavours to commercialise drug delivery smart capsules, the current rise in demand and recent advancements in component development, manufacturing, and miniaturisation have reignited interest in ingestible devices. Consequently, this review analyses the advancements in various mechanical and electrical components associated with ingestible smart drug delivery capsules. These components include modules for device localisation, actuation and retention within the GI tract, signal transmission, drug release, power supply, and payload storage. Challenges and constraints associated with previous capsule design functionality are presented, followed by a critical outlook on future design considerations to ensure efficient and reliable site-specific delivery for the local treatment of GI disorders., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Brendan T. Griffin and Joseph P. O'Shea report financial support was provided by University College Cork. Sophia V. Hoffmann, Brendan T. Griffin, Joseph P. O'Shea, and Vincent Jannin report financial support was provided under the GENEGUT project funded by the European Commission as a Horizon Europe Research and Innovation Action (RIA). Paul Galvin was supported by grants from Science Foundation Ireland (SFI/12/RC/2289-P2) and the European Commission (Grant agreement No. 101057525). Vincent Jannin reports a relationship with Capsugel Colmar that includes: employment. Paul Galvin reports a relationship with Tyndall National Institute that includes: employment. Brendan T. Griffin and Joseph P. O'Shea report a relationship with University College Cork that includes: employment. There are no other known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The aim of the present study was to assess the effects of different levels of hempseed (HS) on growth performance, immunity and gut health in broiler chickens. A total of 192 Hubbard broiler chicks were divided into four groups and fed HS as follow: control (HS0), HS 10% (HS-10), HS 15% (HS-15) and HS 20% (HS-20). The study on HS supplementation in broilers revealed no significant impacts on feed intake during the starter ( p  = .2294) and finisher phases ( p  = .2294), or overall ( p  = .0944), though numerical increases were noted with higher HS levels. Body weight gain showed no significant influence in the starter and finisher phases, with overall weight gain also not significantly different ( p  = .0944), but numerically higher with increased HS. Feed conversion ratio was unaffected in the starter ( p  = .6986) and finisher phases ( p  = .6425), and overall ( p  = .2218). Dressing percentage ( p  = .1062) and mortality ( p  = .1631) were not significantly altered, but HS-20 had the highest dressing percentage and lowest mortality numerically. White blood cell counts increased significantly ( p  = .0377), especially in HS-15 and HS-20 groups. IgM and IgG production was higher in HS-20 on day 28 ( p  = .021). Gut pH ( p  > .05) and intestinal histomorphology ( p  > .05) were not significantly affected, although villus height increased numerically with higher HS levels. These results suggest potential benefits of HS, especially at higher inclusion levels. In conclusion, the obtained results indicated that HS incorporation into the diet of broilers did not affect the growth performance and gut health; however, the immune responses were significantly higher at 15 and 20% levels.

Object: To investigate the effects of Shen Qi Bu Qi Powder (SQBQP) on the average daily gain, blood indexes, gastrointestinal microflora, and serum metabolites of calves., Methods: A total of 105 calves were randomly assigned to three groups (n = 35 per group): the control group (C, fed with a basal diet for 21 days) and two treatment groups (SQBQP-L and SQBQP-H, fed with the basal diet supplemented with 15 and 30 g/kg of SQBQP), respectively for 21 days. The active components of SQBQP were identified using LC-MS/MS. Serum digestive enzymes and antioxidant indices were determined by ELISA kits and biochemical kits, respectively. Serum differential metabolites were analyzed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS), while flora in rumen fluid and fecal were analyzed by 16S rDNA sequencing. Further correlation analysis of gastrointestinal flora and serum metabolites of SQBQP-H and C groups were performed with Spearman's correlation., Results: The principal active components of SQBQP mainly includes polysaccharides, flavonoids, and organic acids. Compared to the control group (C), calves in the SQBQP-H (high dose) and SQBQP-L (low dose) groups showed a significant increase in serum amylase (AMS) levels ( P <0.001), while lipase content significantly decreased ( P <0.05). Additionally, the average daily gain, T-AOC, and cellulase content of calves in the SQBQP-H group significantly increased ( P <0.05). Proteobacteria and Succinivibrio in the rumen flora of the SQBQP-H group was significantly lower than that of the C group ( P <0.05). The relative abundance of Proteobacteria, Actinobacteria, Candidatus&#95;Saccharibacteria, Deinococcus&#95;Thermus, Cyanobacteria , and Succinivibrio in the SQBQP-H group was significantly increased ( P <0.05), while the relative abundance of Tenericutes and Oscillibacter was significantly decreased ( P <0.05). Serum metabolomics analysis revealed 20 differential metabolites, mainly enriched in amino acid biosynthesis, β-alanine metabolism, tyrosine, and tryptophan biosynthesis metabolic pathways ( P <0.05). Correlation analysis results showed that Butyrivibrio in rumen flora and Oscillibacter&#95;valericigenes in intestinal flora were significantly positively correlated with average daily gain, serum biochemical indexes, and differential metabolite (-)-Epigallocatechin (R>0.58, P <0.05)., Conclusion: SQBQP can promote calves weight gain and enhance health by modulating gastrointestinal flora and metabolic processes in the body., Competing Interests: Author XZ was employed by Zhangye Wanhe Animal Husbandry Industry Technology Development Co. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Yang, Ren, Ji, Zhang, Mai, Li, Zhao, Ma, Zhu, Hua and Wei.)

The present study delved into the chemical composition, antioxidant, and anti-inflammatory properties of three dry edible beans: Black (BL), Great Northern (GN), and Pinto (PN). The beans were soaked, cooked, and subjected to in vitro gastrointestinal (GI) digestion. BL bean exhibited significantly higher gastric (42%) and intestinal (8%) digestion rates. Comparative assessment of soluble GI-digested fractions (<3 kDa) revealed that the GN bean exhibited the highest abundance of dipeptides ( P < 0.05). The BL bean fraction displayed a 4-fold increase in tripeptides ( P < 0.05). Both BL and PN bean fractions are high in essential free amino acids, flavonols, and derivatives of hydroxybenzoic acid when compared to the GN bean. All the beans exhibited the ability to mitigate TNF-α-induced pro-inflammatory signaling; however, the BL bean fraction was the most effective at lowering AAPH-induced oxidative stress in HT-29 cells, followed by the GN bean ( P < 0.05). In contrast, a low antioxidant effect was observed with PN beans.

Mammoth study in Chinese villages shows antibiotics that kill Helicobacter pylori reduced cancer risk.

Mycophenolate mofetil (MMF) is commonly utilized for the treatment of neuromyelitis optica spectrum disorders (NMOSD). However, a subset of patients experience significant gastrointestinal (GI) adverse effects following MMF administration. The present study aims to elucidate the underlying mechanisms of MMF-induced GI toxicity in NMOSD. Utilizing a vancomycin-treated mouse model, we compiled a comprehensive data set to investigate the microbiome and metabolome in the GI tract to elucidate the mechanisms of MMF GI toxicity. Furthermore, we enrolled 17 female NMOSD patients receiving MMF, who were stratified into non-diarrhea NMOSD and diarrhea NMOSD (DNM) groups, in addition to 12 healthy controls. The gut microbiota of stool samples was analyzed using 16S rRNA gene sequencing. Vancomycin administration prevented weight loss and tissue injury caused by MMF, affecting colon metabolomes and microbiomes. Bacterial β-glucuronidase from Bacteroidetes and Firmicutes was linked to intestinal tissue damage. The DNM group showed higher alpha diversity and increased levels of Firmicutes and Proteobacteria. The β-glucuronidase produced by Firmicutes may be important in causing gastrointestinal side effects from MMF in NMOSD treatment, providing useful information for future research on MMF., Importance: Neuromyelitis optica spectrum disorder (NMOSD) patients frequently endure severe consequences like paralysis and blindness. Mycophenolate mofetil (MMF) effectively addresses these issues, but its usage is hindered by gastrointestinal (GI) complications. Through uncovering the intricate interplay among MMF, gut microbiota, and metabolic pathways, this study identifies specific gut bacteria responsible for metabolizing MMF into a potentially harmful form, thus contributing to GI side effects. These findings not only deepen our comprehension of MMF toxicity but also propose potential strategies, such as inhibiting these bacteria, to mitigate these adverse effects. This insight holds broader implications for minimizing complications in NMOSD patients undergoing MMF therapy., Competing Interests: The authors declare no conflict of interest.

Background: Gastrointestinal severe adverse events such as ulceration and perforation have been reported for sodium or calcium polystyrene sulfonate and sevelamer. Howewer, their role in the pathogenesis is unclear. Chronic kidney disease is a well known risk factor, while the role of hypertension and/or diabetes is uncertain., Methods: A meta-analysis of the published literature was conducted to review the clinical features, risk factors and histopathological findings of patients who experienced gastrointestinal adverse events after administration of polystyrene sulfonate or sevelamer., Results: The meta-analysis indicated that patients were more likely to show necrosis and/or perforation when the resin used was polystyrene sulfonate compared to sevelamer (p < 0.001). Death was more likely in patients taking polystyrene sulfonate compared to sevelamer (p < 0.001)., Discussion: The results show that sevelamer is more likely to lead to inflammation or ulceration in the gastrointestinal tract than polystyrene sulfonate, which is more likely to be associated with severe gastrointestinal adverse events such as necrosis and/or perforation. Polystyrene sulfonate is significantly associated with death compared to sevelamer., (Copyright © 2024 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

In traditional Chinese medicine, Lycium barbarum is of rich medicinal value, and its polysaccharides are particularly interesting due to their significant pharmacological effects and potential health benefits. This study investigated the immunomodulatory effects of Lycium barbarum polysaccharides (LBPs) by examining their interaction with the TLR4/MD-2 complex and the impacts of gastrointestinal digestion on these interactions. We discovered that the affinity binding of LBPs for TLR4/MD-2 and their cytokine induction capability are influenced by molecular weight, with medium-sized LBPs (100-300 kDa) exhibiting stronger binding affinity and induction capability. Conversely, LBPs smaller than 10 kDa showed reduced activity. Additionally, the content of arabinose and galactose within the LBPs fractions was found to correlate positively with both receptor affinity and cytokine secretion. Simulated gastrointestinal digestion resulted in the degradation of LBPs into smaller fragments that are rich in glucose. Although these fragments exhibited decreased binding affinity to the TLR4/MD-2 complex, they maintained their activity to promote cytokine production. Our findings highlight the significance of molecular weight and specific monosaccharide composition in the immunomodulatory function of LBPs and emphasize the influence of gastrointestinal digestion on the effects of LBPs. This research contributes to a better understanding of the mechanisms underlying the immunomodulatory effects of traditional Chinese medicine polysaccharides and their practical application., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Most animals have large amounts of the special substance melatonin, which is controlled by the light/dark cycle in the suprachiasmatic nucleus. According to what is now understood, the gastrointestinal tract (GIT) and other areas of the body are sites of melatonin production. According to recent studies, the GIT and adjacent organs depend critically on a massive amount of melatonin. Not unexpectedly, melatonin's many biological properties, such as its antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-metastasis, and antiangiogenic properties, have drawn the attention of researchers more and more. Because melatonin is an antioxidant, it produces a lot of secretions in the GIT's mucus and saliva, which shields cells from damage and promotes the development of certain GIT-related disorders. Melatonin's ability to alter cellular behavior in the GIT and other associated organs, such as the liver and pancreas, is another way that it functions. This behavior alters the secretory and metabolic activities of these cells. In this review, we attempted to shed fresh light on the many roles that melatonin plays in the various regions of the gastrointestinal tract by focusing on its activities for the first time., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Poor stability during gastrointestinal digestion is a major challenge for the applications of protein-based nanoparticles as oral delivery systems. In this work, genipin was used to crosslink the partially enzymatic hydrolyzed soy protein nanoparticles, aiming to improve their performance in gastrointestinal tract as delivery carrier. Results showed that the obtained genipin-crosslinked soy protein nanoparticles (GSPNPs) were still spherically monodisperse with a diameter around 60 nm. Encapsulation with GSPNPs significantly improved the solubility of curcumin (Cur) and its stability against UV light as well as long-term storage. Compared to those un-crosslinked nanoparticles, particles crosslinked by genipin had a more compact structure less sensitive to ionic effect and digestive enzymes, showing enhanced digestion stability. The well-maintained nanoparticulate structure of GSPNPs further contributed to the enhanced bioaccessibility and facilitated absorption by epithelial cells. Furthermore, in vivo experiment on rats showed that Cur encapsulated in GSPNPs exhibited a slowed down and sustained absorption manner with an 8.11-fold improvement in its bioavailability. These suggested that GSPNPs could be a promising nanocarrier to enhance the bioavailability of functional factors., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Phenylbutazone (PBZ) is a widely used nonsteroidal anti-inflammatory drug for horses. However, because of its gastrointestinal side effects, its administration requires careful attention in veterinary practice. Malondialdehyde (MDA) is a serum biomarker associated with increased damage to the equine gastrointestinal system. This study investigated the hematological effects and alterations in the gastrointestinal tract and assessed serum MDA concentrations following repeated oral PBZ administration at clinical doses. Fourteen horses were randomly divided into control and treatment groups. All horses in the treatment group were administered 4.4 milligrams per kilogram of body weight of PBZ syrup orally twice a day for 7 days, whereas the control group received syrup as a placebo. The development of gastrointestinal side effects was investigated using gastroscopy, abdominal ultrasound, and fecal pH; serum MDA concentrations were assessed using a commercially available enzyme-linked immunosorbent assay kit. Data were compared between PBZ-treated and control horses before and after the treatment period. The treatment group exhibited decreased albumin and total protein concentrations. Moreover, this group exhibited a higher thickness of the right dorsal colon wall (p = 0.03) and had higher scores for squamous gastric ulcers (p = 0.01). Fecal pH was lower in the treatment group than in the control group after PBZ administration (p < 0.01). Although MDA concentrations were higher in the treatment group after PBZ administration, they did not differ significantly from those of the control group. This study highlighted the changes in hematological and gastrointestinal lesions resulting from PBZ administration in horses at clinical doses, even without clinical signs. However, MDA may not be an optimal biomarker for the early detection of gastrointestinal damage due to PBZ treatment in horses., (© 2024. The Author(s).)

Background: Toxins of Bacillus thuringiensis subsp. israelensis (Bti) are safer alternatives for controlling dipteran pests such as black flies and mosquitoes. The biting midge Culicoides sonorensis (Diptera: Ceratopogonidae) is an important pest of livestock in much of the United States and larval midges utilize semi-aquatic habitats which are permissive for Bti product application. Reports suggest that Bti products are ineffective at killing biting midges despite their taxonomic relation to black flies and mosquitoes. Here, we investigate the toxicity of a Bti-based commercial insecticide and its active ingredient in larval Culicoides sonorensis. A suspected mechanism of Bti tolerance is an acidic larval gut, and we used a pH indicator dye to examine larval Culicoides sonorensis gut pH after exposure to Bti., Results: The lethal concentration to kill 90% (LC 90 ) of larvae of the commercial product (386 mg/L) was determined to be almost 10 000 times more than that of some mosquito species, and no concentration of active ingredient tested achieved 50% larval mortality. The larval gut was found to be more acidic after exposure to Bti which inhibits Bti toxin activity. By comparison, 100% mortality was achieved in larval Aedes aegypti at the product's label rate for this species and mosquito larvae had alkaline guts regardless of treatment. Altering the larval rearing water to alkaline conditions enhanced Bti efficacy when using the active ingredient., Conclusion: We conclude that Bti is not practical for larval Culicoides sonorensis control at the same rates as mosquitos but show that alterations or additives to the environment could make the products more effective. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

The gut-brain axis plays an important role in Parkinson's disease (PD) by acting as a route for vagal propagation of aggregated α-synuclein in the gut-first endophenotype and as a mediator of gastrointestinal dyshomeostasis via the nigro-vagal pathway in the brain-first endophenotype of the disease. One important mechanism by which the gut-brain axis may promote PD is by regulating gastrointestinal redox homeostasis as overwhelming evidence suggests that oxidative stress plays a key role in the etiopathogenesis and progression of PD and the gastrointestinal tract maintains redox homeostasis of the organism by acting as a critical barrier to environmental and microbiological electrophilic challenges. The present aim was to utilize the bilateral intrastriatal 6-hydroxydopamine (6-OHDA) brain-first PD model to study the effects of isolated central pathology on redox homeostasis of the gastrointestinal tract. Three-month-old male Wistar rats were either not treated (intact controls; CTR) or treated bilaterally intrastriatally with vehicle (CIS) or 6-OHDA (6-OHDA). Motor deficits were assessed with the rotarod performance test, and the duodenum, ileum, and colon were dissected for biochemical analyses 12 weeks after the treatment. Lipid peroxidation, total antioxidant capacity, low-molecular-weight thiols, and protein sulfhydryls, the activity of total and Mn/Fe superoxide dismutases, and total and azide-insensitive catalase/peroxidase were measured. Both univariate and multivariate models analyzing redox biomarkers indicate that significant disturbances in gastrointestinal redox balance are not present. The findings demonstrate that motor impairment observed in the brain-first 6-OHDA model of PD can occur without concurrent redox imbalances in the gastrointestinal system., (© 2024. The Author(s).)

Fat and its hydrolysis products, fatty acids, are indispensable nutritional components; however, prolonged excessive fat consumption, particularly in western diets, contributes to the onset of obesity and multiple metabolic disorders. In this study, we propose a daily-ingestible hydrogel (denoted as βC-MA hydrogel) composed of natural β-glucan and sodium carboxymethylcellulose crosslinked by malic acid at 120 °C. This hydrogel exhibits rapid swelling performance, up to 24-fold within 1 min and 176-fold after 1 h in deionized water. It also lengthens gastric retention and increases endogenous satiety signal levels, potentially controlling appetite and reducing food intake. Furthermore, βC-MA hydrogels that enter the small intestine can effectively inhibit fat hydrolysis and decrease triglyceride synthesis and transport. Specifically, the hydrogels inhibit the release of free fatty acids (FFAs) by approximately 50 % during digestion, influence the translocation of triglycerides and FFAs across the intestinal epithelium, and reduce the serum triglyceride levels by 22.2 %. These findings suggest that βC-MA hydrogels could serve as a noninvasive gastrointestinal device for weight control, with the advantage of reducing food intake and restoring lipid metabolism homeostasis., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Polycyclic aromatic hydrocarbons (PAHs) are a large group of organic compounds which are comprised of two or more fused benzene rings. As a typical environmental pollutant, PAHs are widely distributed in water, soil, atmosphere and food. Despite extensive researches on the mechanisms of health damage caused by PAHs, especially their carcinogenic and mutagenic toxicity, there is still a lack of comprehensive summarization and synthesis regarding the mechanisms of PAHs on the gut-testis axis, which represents an intricate interplay between the gastrointestinal and reproductive systems. Thus, this review primarily focuses on the potential forms of interaction between PAHs and the gut microbiota and summarizes their adverse outcomes that may lead to gut microbiota dysbiosis, then compiles the possible mechanistic pathways on dysbiosis of the gut microbiota impairing the male reproductive function, in order to provide valuable insights for future research and guide further exploration into the intricate mechanisms underlying the impact of gut microbiota dysbiosis caused by PAHs on male reproductive function., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose including employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, and grants or other funding., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: This study sought to evaluate the late toxicity associated with neoadjuvant and concurrent docetaxel and radiation therapy in patients with prostate cancer., Methods: A secondary analysis was performed of the phase 3 multicenter randomized trial (Dana-Farber Cancer Institute 05-043) including 350 patients with nonmetastatic unfavorable-risk prostate cancer. Patients were randomized 1:1 to receive androgen deprivation therapy, radiation therapy, and docetaxel versus androgen deprivation therapy and radiation therapy. The study assessed the cumulative incidence rates of grade 2 and grade 3 or higher gastrointestinal, genitourinary, and sexual toxicity. A multivariable Fine and Gray's competing risks regression model adjusted for age at randomization and pelvic lymph node radiation therapy was used to evaluate the treatment effect of docetaxel on time to late genitourinary and gastrointestinal toxicities., Results: The study included 338 patients who primarily had minimal or no comorbidity (74.9%) and median age 66 years (interquartile range: 61,71). At a median follow-up of 10.2 years, docetaxel was not associated with increased risk of any grade 3 or higher (adjusted hazard ratio [AHR], 0.98; 95% confidence interval [CI], 0.36-2.67; p = .96) or grade 2 gastrointestinal (p = .75), genitourinary (p = .44), and sexual (p = .29) toxicity. Age was associated with increased grade 3 or higher (AHR, 1.08; 95% CI, 1.01-1.16; p = .03) and grade 2 gastrointestinal toxicity (AHR, 1.11; 95% CI, 1.03-1.20; p = .005). A nonsignificant trend (p = .09) toward increased late grade 3 or higher toxicity was observed for pelvic radiation therapy use., Conclusions: Docetaxel combined with radiotherapy has an acceptable long-term toxicity profile., (© 2024 American Cancer Society.)

Biodegradable plastics, hailed for their environmental friendliness, may pose unforeseen risks as they undergo gastrointestinal degradation, forming oligomer nanoplastics. Despite this, the influence of gastrointestinal degradation on the potential human toxicity of biodegradable plastics remains poorly understood. To this end, the impact of the murine in vivo digestive system is investigated on the biotransformation, biodistribution, and toxicity of PLA polymer and PLA oligomer MPs. Through a 28-day repeated oral gavage study in mice, it is revealed that PLA polymer and oligomer microplastics undergo incomplete and complete degradation, respectively, in the gastrointestinal tract. Incompletely degraded PLA polymer microplastics transform into oligomer nanoplastics, heightening bioavailability and toxicity, thereby exacerbating overall toxic effects. Conversely, complete degradation of PLA oligomer microplastics reduces bioavailability and mitigates toxicity, offering a potential avenue for toxicity reduction. Additionally, the study illuminates shared targets and toxicity mechanisms in Parkinson's disease-like neurotoxicity induced by both PLA polymer and PLA oligomer microplastics. This involves the upregulation of MICU3 in midbrains, leading to neuronal mitochondrial calcium overload. Notably, neurotoxicity is mitigated by inhibiting mitochondrial calcium influx with MCU-i4 or facilitating mitochondrial calcium efflux with DBcAMP in mice. These findings enhance the understanding of the toxicological implications of biodegradable microplastics on human health., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Background: β-casein is the main casein constituent in human milk (HM) and a source of bioactive peptides for the developing gastrointestinal tract and immune system. Infant formulas contain less β-casein than HM, but whether different concentrations of β-casein affect tolerability and gut and immune maturation in newborns is unknown., Objectives: Using near-term piglets as a model for newborn infants, we investigated whether increasing the β-casein fraction in bovine-based formula is clinically safe and may improve gut and immune maturation., Methods: Three groups of near-term pigs (96% gestation) were fed formula with bovine casein and whey protein (ratio 40:60): 1) standard skim milk casein (BCN-standard, 35% β-casein of total casein, n = 18); 2) β-casein enrichment to HM concentrations (BCN-medium, 65%, n = 19); and 3) high β-casein enrichment (BCN-high, 91%, n = 19). A reference group was fed 100% whey protein concentrate (WPC) as protein (WPC, n = 18). Intestinal and immune parameters were assessed before and after euthanasia on day 5., Results: Clinical variables (mortality, activity, body growth, and diarrhea) were similar among the groups, and no differences in intestinal or biochemical parameters were observed between BCN-standard and BCN-medium pigs. However, pigs receiving high amounts of β-casein (BCN-high) had lower small intestine weight and tended to have more intestinal complications (highest gut pathology score, permeability, and interleukin-8) than the other groups, particularly those receiving no casein (WPC pigs). Blood lymphocyte, thrombocyte, and reticulocyte counts were increased with higher β-casein, whereas eosinophil counts were reduced. In vitro blood immune cell responses were similar among groups., Conclusions: β-casein enrichment of bovine-based formula to HM concentrations is clinically safe, as judged from newborn, near-term pigs, whereas no additional benefits to gut maturation were observed. However, excessive β-casein supplementation, beyond concentrations in HM, may potentially induce gut inflammation together with increased blood cell populations relative to natural β-casein concentrations or pure whey-based formula., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

To improve probiotics' survivability during gastrointestinal digestion and heat treatment, Lactobacillus plantarum was microencapsulated by spray-drying using Laminaria japonica polysaccharide/sodium caseinate/gelatin (LJP/SC/GE) composites. Thermogravimetry and differential scanning calorimetry results revealed that the denaturation of LJP/SC/GE microcapsules requires higher thermal energy than that of SC/GE microcapsules, and the addition of LJP may improve thermal stability. Zeta potential measurements indicated that, at low pH of the gastric fluid, the negatively charged LJP attracted the positively charged SC/GE, helping to maintain an intact microstructure without disintegration. The encapsulation efficiency of L. plantarum -loaded LJP/SC/GE microcapsules reached about 93.4%, and the survival rate was 46.9% in simulated gastric fluid (SGF) for 2 h and 96.0% in simulated intestinal fluid (SIF) for 2 h. In vitro release experiments showed that the LJP/SC/GE microcapsules could protect the viability of L. plantarum in SGF and release probiotics slowly in SIF. The cell survival of LJP/SC/GE microcapsules was significantly improved during the heat treatment compared to SC/GE microcapsules and free cells. LJP/SC/GE microcapsules can increase the survival of L. plantarum by maintaining the lactate dehydrogenase and Na + -K + -ATPase activity. Overall, this study demonstrates the great potential of LJP/SC/GE microcapsules to protect and deliver probiotics in food and pharmaceutical systems.

Changing eating habits and an increase in consumption of thermally processed products have increased the risk of the harmful impact of chemical substances in food on consumer health. A 2002 report by the Swedish National Food Administration and scientists at Stockholm University on the formation of acrylamide in food products during frying, baking and grilling contributed to an increase in scientific interest in the subject. Acrylamide is a product of Maillard's reaction, which is a non-enzymatic chemical reaction between reducing sugars and amino acids that takes place during thermal processing. The research conducted over the past 20 years has shown that consumption of acrylamide-containing products leads to disorders in human and animal organisms. The gastrointestinal tract is a complex regulatory system that determines the transport, grinding, and mixing of food, secretion of digestive juices, blood flow, growth and differentiation of tissues, and their protection. As the main route of acrylamide absorption from food, it is directly exposed to the harmful effects of acrylamide and its metabolite-glycidamide. Despite numerous studies on the effect of acrylamide on the digestive tract, no comprehensive analysis of the impact of this compound on the morphology, innervation, and secretory functions of the digestive system has been made so far. Acrylamide present in food products modifies the intestine morphology and the activity of intestinal enzymes, disrupts enteric nervous system function, affects the gut microbiome, and increases apoptosis, leading to gastrointestinal tract dysfunction. It has also been demonstrated that it interacts with other substances in food in the intestines, which increases its toxicity. This paper summarises the current knowledge of the impact of acrylamide on the gastrointestinal tract, including the enteric nervous system, and refers to strategies aimed at reducing its toxic effect.

High failure rates of the current drug development process are driving exemplary changes toward methodologies centered on human disease in-vitro modeling. Organoids are self-organized tissue sub-units resembling their organ of origin and are widely acknowledged for their unique potential in recapitulating human physio-pathological mechanisms. They are transformative for human health by becoming the platform of choice to probe disease mechanisms and advance new therapies. Furthermore, the compounds' validation as therapeutics represents another point of the drug development pipeline where organoids may provide key understandings and help pharma organizations replace or reduce animal research. In this review, we focus on gastrointestinal organoid models, which are currently the most advanced organoid models in drug development. We focus on experimental validations of their value, and we propose avenues to enhance their use in drug discovery and development, as well as precision medicine and diagnostics., (© 2024 IOP Publishing Ltd.)

Survival strategies of human-associated microbes to drug exposure have been mainly studied in the context of bona fide pathogens exposed to antibiotics. Less well understood are the survival strategies of non-pathogenic microbes and host-associated commensal communities to the variety of drugs and xenobiotics to which humans are exposed. The lifestyle of microbial commensals within complex communities offers a variety of ways to adapt to different drug-induced stresses. Here, we review the responses and survival strategies employed by gut commensals when exposed to drugs-antibiotics and non-antibiotics-at the individual and community level. We also discuss the factors influencing the recovery and establishment of a new community structure following drug exposure. These survival strategies are key to the stability and resilience of the gut microbiome, ultimately influencing the overall health and well-being of the host., Competing Interests: Declaration of interests L.M. is listed as a co-inventor on the following patents (or patent applications): EP3838269A (published 23.06.2021) Compounds & Pharmaceutical Compositions for Prevention-Treatment of Dysbiosis, Antidotes for Microbiome Prevention; WO/2019/158559 (published 22.08.2019) Repurposing compounds for the treatment of infections and for modulating the composition of the gut microbiome; and WO/2019/154823 (published in 15.08.2019) In vitro model of the human gut microbiome and uses thereof in the analysis of the impact of xenobiotics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

It is common knowledge that prolonged and excessive use of antibiotics can lead to antimicrobial resistance. However, the characteristics and mechanism of resistant-bacteria induced by clinically recommended and prophylactic dose drugs remain largely unclear. This study aimed to observe the trends of drug resistance of the bacitracin-susceptible Staphylococcus aureus strain FS127 under exposure to bacitracin (BAC), which were induced in vitro and in chicken gut. Antimicrobial susceptibility testing was used to detect the susceptibility of S. aureus induced in vitro and in the chicken gut to gentamicin, chloramphenicol, tetracycline, doxycycline, penicillin and chloramphenicol. The research results showed that bacitracin could induce drug resistance in S. aureus both in vitro and in vivo. The bacitracin-resistance rate of S. aureus isolated from chicken gut was positively correlated with the dose and time of bacitracin administration. The findings revealed that bacitracin-resistant S. aureus induced in vivo had enhanced susceptibility to chloramphenicol but no such change in vitro. Meanwhile, RT-qPCR assay was used to detect the expression levels of vraD, braD, braR and bacA in typical strains with different bacitracin-resistance levels. It was found that BacA may play a key role in the bacitracin resistance of S. aureus. In conclusion, this work reveals the characteristics and mechanism of bacitracin-resistant S. aureus induced by bacitracin in vivo and in vitro respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study investigated the effects of the early administration of enrofloxacin (E) or doxycycline (D) for the first 5 consecutive days of life, or the continuous administration of the coccidiostat monensin (M) throughout the rearing period on gastrointestinal function in turkeys infected with avian pathogenic Escherichia coli (APEC) in an early or later stage of rearing. Experiment 1 lasted 21 d, and turkeys in groups E, D, and M were infected with APEC on d 15. Experiment 2 lasted 56 d, and it had a factorial arrangement of treatments where birds in groups E, D, and M were infected with APEC on d 15 or d 50. In both experiments, control groups (C) consisted of infected and uninfected birds without antibiotic or coccidiostat administration. On d 21 (Experiment 1) and d 56 (Experiment 2), 8 birds from each subgroup were killed, and the ileal and cecal digesta were sampled to analyze the activity of bacterial enzymes and the concentrations of short-chain fatty acids (SCFA). The experimental treatments did not affect the final body weight or body weight gain of birds. Both experiments demonstrated that APEC contributed to an increase in ammonia levels of the cecal digesta (means from 2 experiments: 0.311 vs. 0.225 mg/g in uninfected birds) and ileal pH (6.79 vs. 6.00) and viscosity (2.43 vs. 1.83 mPa⋅s). Moreover, the E. coli challenge enhanced the extracellular activity of several cecal bacterial enzymes, especially in older turkeys infected with APEC in a later stage of life. The continuous administration of monensin throughout the rearing period resulted in a weaker gastrointestinal response in older birds, compared with the other 2 antibiotics administered for the first 5 d of life. The results of the study are inconclusive as both desirable and undesirable effects of preventive early short-term antibiotic therapy were observed in turkeys, including normalization of ileal viscosity and cecal ammonia concentration (positive effect), and disruption in cecal SCFA production (negative effect)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cry1Ab has emerged as a bio-insecticide to control Spodoptera litura (Lepidoptera: Noctuidae). However, the sublethal effects of Cry1Ab on the physiological changes and molecular level of S. litura have not been well documented. Our aims in this study were to assess the sublethal effect of Cry1Ab on S. litura, including midgut and Malpighian tubules as targets., Results: After sublethal Cry1Ab exposure, distinct histological alterations were mainly observed in the midgut. Furthermore, the results of comparative RNA sequencing and tandem mass tag-based proteomics showed that, in the midgut, most differential expression genes (DEGs) were up-regulated and significantly enriched in the serine protease activity pathway, and up-regulated differential expression proteins (DEPs) were mainly associated with the oxidative phosphorylation pathway, whereas the down-regulated involved in the ribosome pathways. In the Malpighian tubules, DEGs and DEPs were significantly enriched in the ribosome pathway. We proposed that ribosome may act as a universal target in energy metabolism with other pathways via the results of protein-protein interaction analysis. Further, by verification of the mRNA expression of some Cry protein receptor and detoxification genes after Cry1Ab treatment, it was suggested that the ribosomal proteins (RPs) possibly participate in influencing the Bt-resistance of S. litura larvae under sublethal Cry1Ab exposure., Conclusion: Under sublethal Cry1Ab exposure, the midgut of S. litura was damaged, and the proteotranscriptomic analysis elucidated that Cry1Ab disrupted the energy homeostasis of larvae. Furthermore, we emphasized the potential role of ribosomes in sublethal Cry1Ab exposure. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Safety and efficacy are the most critical factors for the development of modern medications. For oral drugs, evaluating drug exposure under various conditions is one of the most important outcomes for clinical trials. These data will help to better understand the safety and efficacy of new drugs. Studies involving potential drug-drug interactions, proton pump inhibitors, and intake of food are often conducted to assess the above. Among the above, the influence of food on exposure to the drug is one of the key data sets for regulatory submission. Since food may have either a positive or negative effect on drug exposure, it is important to obtain an early assessment of the food effect. To better forecast and plan for clinical studies, substantial efforts have been made in the industry to develop modeling and in-vitro and in-vivo assays. Despite the efforts, predicting the effect of food on exposure without integrating the dynamic of the gastrointestinal tract in the assessment remains challenging. In this study, we evaluated the utilization of the dynamic Gastro-Intestinal Model (Tiny-TIM) for the food effect of over 20 drugs/formulations in development or on the market that covers all BCS classes. In general, the Tiny-TIM predicted food effects were in good agreement with the reported data in humans. This suggests that Tiny-TIM can successfully capture the impact of physicochemical properties on absorption under the influence of food., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)