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Simple Summary: Weaning is a challenging stage for piglets, involving sudden changes in diet, environment, and social interactions, which place stress on their digestive and immune systems. In commercial pig farming, early weaning often leads to immature gut development, making piglets more vulnerable to health issues like post-weaning diarrhoea. This review discusses natural dietary nutrient strategies to help piglets transition smoothly through weaning without relying on antimicrobials. Lowering crude protein in piglet diets can reduce undigested proteins in the gut, which helps prevent harmful bacteria from causing digestive problems. Adding organic acids to the diet helps maintain a healthy stomach pH, improves digestion, and supports a balanced gut microbiome. Another approach is to boost gut health with butyrate, a beneficial compound that reduces inflammation and protects the gut lining. Butyrate can be provided directly or encouraged naturally by promoting beneficial gut bacteria. These strategies present promising approaches to enhancing piglet health during weaning, although further research is necessary to achieve consistent outcomes. Combining these strategies may provide an effective solution to improving growth, gut health, and the overall sustainability of post-weaned pig production. Weaning in piglets presents significant physiological and immunological challenges, including gut dysbiosis and increased susceptibility to post-weaning diarrhoea (PWD). Abrupt dietary, environmental, and social changes during this period disrupt the intestinal barrier and microbiota, often necessitating antimicrobial use. Sustainable dietary strategies are critical to addressing these issues while reducing reliance on antimicrobials. Reducing dietary crude protein mitigates the availability of undigested proteins for pathogenic bacteria, lowering harmful by-products like ammonia and branched-chain fatty acids, which exacerbate dysbiosis. Organic acid supplementation improves gastric acidification, nutrient absorption, and microbial balance, while also serving as an energy-efficient alternative to traditional grain preservation methods. Increasing intestinal butyrate, a key short-chain fatty acid with anti-inflammatory and gut-protective properties, is particularly promising. Butyrate strengthens intestinal barrier integrity by upregulating tight junction proteins, reduces inflammation by modulating cytokine responses, and promotes anaerobic microbial stability. Exogenous butyrate supplementation via salts provides immediate benefits, while endogenous stimulation through prebiotics (e.g., resistant starch) and probiotics promotes sustained butyrate production. These interventions selectively enhance butyrate-producing bacteria such as Roseburia and Faecalibacterium prausnitzii, further stabilising the gut microbiota. Integrating these strategies can enhance gut integrity, microbial resilience, and immune responses in weaned piglets. Their combination offers a sustainable, antimicrobial-free approach to improving health and productivity in modern pig production systems. [ABSTRACT FROM AUTHOR]

The coal mine workplace environment is a significant factor in inducing occupational health issues, such as intestinal dysfunction in coal miners. However, the mechanism by which the coal mine workplace environment induces intestinal dysfunction is still unclear. Therefore, we applied the Coal Mine Workplace Environment Biological Simulation (CEBS) model which was previously constructed to detect the intestinal pathological manifestations and changes in the gut microbiota of mice from the perspectives of intestinal function, tissue morphology, and cell molecules. CEBS mice showed increased fecal water content, shortened colon length, significant activation of MPO+ and CD11b+ numbers, and significant changes in IL-1b, IL-6, and IL-12 expression levels. In addition, we also found an imbalance in the proportions of Firmicutes, Bacteroidetes, Lactobacillus , and Parabacteroides in CEBS mice, resulting in significant changes in gut microbial diversity. After intervention with compound probiotics, the intestinal function of CEBS + Mix mice was improved and inflammation levels were reduced. Results indicated that stress in the coal mine workplace environment can lead to intestinal dysfunction and inflammatory damage of the colon and use of compound probiotics can improve intestinal dysfunction in CBES mice. In our study, we revealed that there is a correlation between coal mine workplace environment and diversity disorders of gut microbiota. This discovery has enhanced the relevant theories on the causes of intestinal dysfunction in coal miners and has suggested a new approach to intervention. [ABSTRACT FROM AUTHOR]

Background/Objectives: Injection of lipopolysaccharides (LPS) in experimental models induces a systemic inflammatory response that is associated with deleterious effects on intestinal morphology and physiology. In this study, we have studied in female mice the effects of dietary supplementation with bovine lactoferrin (bLF) given before intraperitoneal injection of LPS on jejunum and colon. Methods: The first study evaluated the efficiency of different bLF and LPS concentrations to determine the optimal experimental conditions. For the second study mice were fed with 1% bLF before the LPS challenge (3 mg/kg body weight). Plasmatic markers of inflammation, intestinal morphology, permeability, and expression of genes related to epithelial differentiation, epithelial barrier function and intestinal inflammation in both small intestine and colon were evaluated. Results: bLF ingestion before the LPS challenge reduced the TNF-α circulating concentration, compared to control animals. This decrease in plasma TNF-α was correlated with improved intestinal permeability. The morphology of jejunal epithelium, which was affected by LPS challenge, was partly maintained by bLF. Measurement of the expression of genes encoding proteins involved in epithelial differentiation, intestinal inflammation, and epithelial barrier function suggests an overall protective effect of bLF against the adverse effects of LPS in the jejunum. In the colon, the effects of bLF ingestion on the subsequent LPS challenge, although protective, remain different when compared with those observed on jejunum. Conclusions: Taken together, our data indicate that bLF dietary supplementation does have a protective effect on the deleterious intestinal alterations induced by LPS systemic inflammation. [ABSTRACT FROM AUTHOR]

Background and objectives: Although a reasonable diet is essential for promoting human health, precise nutritional regulation presents a challenge for different physiological conditions. Irritable Bowel Syndrome (IBS) is characterized by recurrent abdominal pain and abnormal bowel habits, and diarrheal IBS (IBS-D) is the most common, seriously affecting patients' quality of life. Therefore, the implementation of precise nutritional interventions for IBS-D has become an urgent challenge in the fields of nutrition and food science. IBS-D intestinal homeostatic imbalance involves intestinal flora disorganization and impaired intestinal epithelial barrier function. A familiar interaction is evident between intestinal flora and intestinal epithelial cells (IECs), which together maintain intestinal homeostasis and health. Dietary patterns, such as the Mediterranean diet, have been shown to regulate gut flora, which in turn improves the body's health by influencing the immune system, the hormonal system, and other metabolic pathways. Methods: This review summarized the relationship between intestinal flora, IECs, and IBS-D. It analyzed the mechanism behind IBS-D intestinal homeostatic imbalance by examining the interactions between intestinal flora and IECs, and proposed a precise dietary nutrient intervention strategy. Results and conclusion: This increases the understanding of the IBS-D-targeted regulation pathways and provides guidance for designing related nutritional intervention strategies. [ABSTRACT FROM AUTHOR]

The coal mine workplace environment is a significant factor in inducing occupational health issues, such as intestinal dysfunction in coal miners. However, the mechanism by which the coal mine workplace environment induces intestinal dysfunction is still unclear. Therefore, we applied the Coal Mine Workplace Environment Biological Simulation (CEBS) model which was previously constructed to detect the intestinal pathological manifestations and changes in the gut microbiota of mice from the perspectives of intestinal function, tissue morphology, and cell molecules. CEBS mice showed increased fecal water content, shortened colon length, significant activation of MPO+ and CD11b+ numbers, and significant changes in IL-1b, IL-6, and IL-12 expression levels. In addition, we also found an imbalance in the proportions of Firmicutes, Bacteroidetes, Lactobacillus, and Parabacteroides in CEBS mice, resulting in significant changes in gut microbial diversity. After intervention with compound probiotics, the intestinal function of CEBS + Mix mice was improved and inflammation levels were reduced. Results indicated that stress in the coal mine workplace environment can lead to intestinal dysfunction and inflammatory damage of the colon and use of compound probiotics can improve intestinal dysfunction in CBES mice. In our study, we revealed that there is a correlation between coal mine workplace environment and diversity disorders of gut microbiota. This discovery has enhanced the relevant theories on the causes of intestinal dysfunction in coal miners and has suggested a new approach to intervention.

IntroductionIntestinal dysfunction poses a severe problem by preventing the digestion and absorption of nutrients. The gut, being the most vital organ for these processes, plays a crucial role in ensuring our body receives the nutrients it needs. We explored the mitigating effect of Morchella esculenta polysaccharides (MEP) on intestinal injury induced by lipopolysaccharides (LPS) through the modulation of intestinal flora.MethodsFor this purpose, Kunming mice (KM) were divided into three groups, namely, PC, PM, and PY. Group PY was treated with MEP, while groups PM and PY were induced with LPS.ResultsThe results showed that weight loss in the PM group was significantly greater than that in the PY group (P < 0.05), and the organ indexes of the lung and spleen in the PM group were significantly higher than those in the PC (P < 0.01) and PY (P < 0.05) groups. LPS caused severe injuries in KM mice in the PM group, characterized by broken villi. However, MEP treatment could alleviate this damage in the PY group, resulting in relatively intact villi. The serum analysis showed that tumor necrosis factor alpha (TNF-ɑ) (P < 0.01), interleukin 6 (IL-6) (P < 0.01), and 3,4-methylenedioxyamphetamine (MDA) (P < 0.05) levels were significantly higher in the PM group, while IL-10 (P < 0.001), superoxide dismutase (SOD) (P < 0.01) and glutathione peroxidase (GSH-Px) (P < 0.01) were significantly lower in that group. Interestingly, supplementation with MEP could lower the levels of TNF-ɑ, IL-10, IL-6, MDA while increasing the levels of superoxide dismutase (SOD) (P < 0.01) and GSH-Px. The gut microbiota analysis yielded 630,323 raw reads and 554,062 clean reads, identifying 3,390 amplicon sequencing variants (ASVs). One phylum and five genera were notably different among animal groups, including Escherichia_Shigella, Limosilactobacillus, unclassified_Geminicoccaceae, unclassified_Rhodobacteraceae, and Parabacteroides (P. distasonis).DiscussionIn conclusion, we found that MEP could mitigate the intestinal damage caused by LPS by modulating the inflammatory response, oxidative resistance, and intestinal flora of KM mice. Our results may provide insights into novel treatment options for intestine-related diseases.

Aging can cause degenerative changes in multiple tissues and organs. Gastrointestinal diseases and dysfunctions are common in the elderly population. In this study, we investigated the effects of Astragalus membranaceus polysaccharide (APS) and Astragalus membranaceus ethanol extract (AEE) on age-related intestinal dysfunction and gut microbiota dysbiosis in naturally aging mice. The energy expenditure and physical activity of 23-month-old C57BL6/J mice were recorded using a metabolic cage system. Pathological changes in the intestine were evaluated using Alcian blue staining. The protein levels of leucine-rich repeats containing G protein-coupled receptor 5 (Lgr5) and Stat3 in the small intestine were determined using immunohistochemistry. The intestinal cell migration distance was assessed using bromodeoxyuridine (BrdU) immunofluorescence staining. The gene transcription levels of intestinal stem cell (ISC) markers and ISC-related signaling pathways were detected using quantitative real-time PCR (qRT-PCR). Microbiota analysis based on 16S rDNA was performed to evaluate the composition of the gut microbiota. APS and AEE improved a series of aging phenotypes in female but not in male aging mice. APS and AEE ameliorate intestinal dysfunction and histopathological changes in aging mice. APS had a more significant anti-aging effect than AEE, particularly on intestinal dysfunction. APS promotes ISC regeneration by activating the IL-22 signaling pathway. Cohousing (CH) experiments further confirmed that APS induced the IL-22 signaling pathway by increasing the abundance of Lactobacillus, thereby promoting the regeneration of ISCs. Our results show that APS may serve as a promising agent for improving age-related intestinal dysfunction. [ABSTRACT FROM AUTHOR]

Objective; To explore the effects and mechanism of Salvianolic acid B (SalB) on Parkinson's disease (PD). Methods; Forty-eight C57BL/6 male mice were randomly separated into control group (control) without drugs, model group (MPTP) with intraperitoneal injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrah-ydropyridine (MPTP), SalB control group with intraperitoneal injection of SalB, and SalB treatment group (MPTP+SalB). Construction of PD mouse model by intraperitoneal injection of MPTP, and treatment with intraperitoneal injection of SalB. Pole climbing test was applied to assess behavior differences. The time of first black stool excretion and water content of feces were measured to evaluate intestinal dysfunctions. The number of tyrosine hydroxylase (TH) positive cells in substantia nigra and the level of Toll like receptor 4(TLR4) in colon were analyzed by immunohistochemistry. The pathological changes of colonic mucosa were observed by HE staining. The levels of calprotectin (CP) and tumor necrosis factor-α (TNF-α) in colon were determined by ELISA. Western blot was used to determine the level of TH in midbrain, the protein level of TH, tight junction protein (ZO-1), and protein level of TLR4/MyD88/NF-κB signaling pathways which express in colon. Results; Compared with the Control group, the climbing time, T-turn time and the first black stool excretion time in MPTP group increased while the fecal water content and the number of TH positive cells in substantia nigra were decreased. Accompanied by TLR4 positive cells in colon, pathological injury score of colonic mucosa, levels of CP and TNF-α in colon increased, expression of TH in midbrain and expression of ZO-1 in colon decreased. Expressions of TLR4, MyD88, Nuclear NF-κB p65 and p-NF-κB p65 in colon increased. Com⁃ pared with MPTP group, SalB treatment shortened the climbing time, T-turn time and the first black stool excretion time in SalB treatment group, increased the fecal water content and the number of TH positive cells in substantia nigra, lowered TLR4 positive cells in colon, enhanced expression of TH in midbrain and colon, reduced the pathological injury score of colonic mucosa, significantly decreased levels of CP and TNF-α in colon, enhanced expression of ZO-1 in colon, inhibited expressions of TLR4, MyD88, Nuclear NF-κB p65 and p-NF-κB p65 in colon. Conclusion; SalB can protect the nerves and intestines and alleviate the intestinal inflammation of PD mice, which may be related to the inhibition of TLR4/MyD88/NF-κB signal pathway. [ABSTRACT FROM AUTHOR]

Simple Summary: The gastrointestinal tract (GIT) is home to a large number of microorganisms, referred to collectively as the GIT microbiota. These microorganisms can be beneficial or potentially harmful to the host. Ensuring a high level of microbial diversity in the GIT, with a high abundance of beneficial and a low abundance of pathogenic microorganisms, is essential for host health. A healthy microbiota is vital at all stages of pig production; however, the post-weaning period is of particular importance. The post-weaning period is a phase during which intestinal dysbiosis can occur, providing an opportunity for harmful microorganisms to colonize and proliferate, leading to poor performance and even mortality. Different microorganisms have different metabolic capabilities, varying in the substrates they break down and the subsequent bioactive metabolites they produce. Therefore, the dietary substrates available to microbes have a significant impact on the microbial composition of the GIT and the subsequent metabolites produced. A prebiotic is a substrate selectively utilized by host microorganisms and conferring a benefit to the host. Prebiotics offer a therapeutic strategy in order to alter the composition of the microbiota, enhancing the proliferation of beneficial microbes and production of host-health-promoting metabolites, which can subsequently limit the proliferation of potentially harmful microbes. There is currently a broad range of different prebiotic classes. These vary in structure and composition and subsequently in the effects exerted on the microbiota. The current review is an overview of the different classes of prebiotics, their potential mode benefits, and the main findings from investigations utilizing them in the pigs' diets to date. Establishing a balanced and diverse microbiota in the GIT of pigs is crucial for optimizing health and performance throughout the production cycle. The post-weaning period is a critical phase, as it is often associated with dysbiosis, intestinal dysfunction and poor performance. Traditionally, intestinal dysfunctions associated with weaning have been alleviated using antibiotics and/or antimicrobials. However, increasing concerns regarding the prevalence of antimicrobial-resistant bacteria has prompted an industry-wide drive towards identifying natural sustainable dietary alternatives. Modulating the microbiota through dietary intervention can improve animal health by increasing the production of health-promoting metabolites associated with the improved microbiota, while limiting the establishment and proliferation of pathogenic bacteria. Prebiotics are a class of bioactive compounds that resist digestion by gastrointestinal enzymes, but which can still be utilized by beneficial microbes within the GIT. Prebiotics are a substrate for these beneficial microbes and therefore enhance their proliferation and abundance, leading to the increased production of health-promoting metabolites and suppression of pathogenic proliferation in the GIT. There are a vast range of prebiotics, including carbohydrates such as non-digestible oligosaccharides, beta-glucans, resistant starch, and inulin. Furthermore, the definition of a prebiotic has recently expanded to include novel prebiotics such as peptides and amino acids. A novel class of -biotics, referred to as "stimbiotics", was recently suggested. This bioactive group has microbiota-modulating capabilities and promotes increases in short-chain fatty acid (SCFA) production in a disproportionally greater manner than if they were merely substrates for bacterial fermentation. The aim of this review is to characterize the different prebiotics, detail the current understating of stimbiotics, and outline how supplementation to pigs at different stages of development and production can potentially modulate the GIT microbiota and subsequently improve the health and performance of animals. [ABSTRACT FROM AUTHOR]

Simple Summary: The gastrointestinal tract (GIT) microbiota refers to the collection of microorganisms that colonize the GIT. The composition and diversity of the GIT microbiota play a fundamental role in animal health and performance and is an area that is becoming increasingly important with recent introduction of new restrictions on antibiotic and antimicrobial use in animal production. Enhancing the establishment of the GIT microbiota in the initial stages of life can improve health and performance, both in the immediate period and later life. Interestingly, the offspring's microbiota is heavily influenced by the maternal microbiota, thereby underlining modulation of the maternal microbiota as a promising strategy to enhance the health and growth of the offspring. A probiotic is a beneficial live microorganism that, when supplemented, has beneficial effects on the host's health. A synbiotic is a combination of a probiotic and another bioactive known as a prebiotic, which is essentially a substrate for beneficial microbes in the gut. Supplementing probiotics or synbiotics in the maternal diet presents a promising strategy to firstly modulate the maternal GIT microbiota, conferring several health benefits to the sow, and secondly to influence the establishment of the offspring's GIT microbiota, conferring several health benefits to the offspring. The current review discusses the importance and suggested mechanisms of action for maternal probiotic and synbiotic supplementation and details key findings from studies that have investigated the effects of maternal probiotic or synbiotic supplementation in pigs. The increasing prevalence of antimicrobial-resistant pathogens has prompted the reduction in antibiotic and antimicrobial use in commercial pig production. This has led to increased research efforts to identify alternative dietary interventions to support the health and development of the pig. The crucial role of the GIT microbiota in animal health and performance is becoming increasingly evident. Hence, promoting an improved GIT microbiota, particularly the pioneer microbiota in the young pig, is a fundamental focus. Recent research has indicated that the sow's GIT microbiota is a significant contributor to the development of the offspring's microbiota. Thus, dietary manipulation of the sow's microbiota with probiotics or synbiotics, before farrowing and during lactation, is a compelling area of exploration. This review aims to identify the potential health benefits of maternal probiotic or synbiotic supplementation to both the sow and her offspring and to explore their possible modes of action. Finally, the results of maternal sow probiotic and synbiotic supplementation studies are collated and summarized. Maternal probiotic or synbiotic supplementation offers an effective strategy to modulate the sow's microbiota and thereby enhance the formation of a health-promoting pioneer microbiota in the offspring. In addition, this strategy can potentially reduce oxidative stress and inflammation in the sow and her offspring, enhance the immune potential of the milk, the immune system development in the offspring, and the sow's feed intake during lactation. Although many studies have used probiotics in the maternal sow diet, the most effective probiotic or probiotic blends remain unclear. To this extent, further direct comparative investigations using different probiotics are warranted to advance the current understanding in this area. Moreover, the number of investigations supplementing synbiotics in the maternal sow diet is limited and is an area where further exploration is warranted. [ABSTRACT FROM AUTHOR]

Abstract Aims We analysed intestinal permeability in patients with chronic Chagas cardiomyopathy (CCC) and evaluated its association with clinical manifestations, haemodynamic parameters measured by echocardiogram, and disease outcome. Intestinal permeability was compared between CCC patients and a group of healthy controls. Background Intestinal dysfunction may contribute to a more severe disease presentation with worse outcome in patients with CCC and heart failure. Methods Fifty patients with CCC and left ventricular ejection fraction (LVEF) of less than 55% were prospectively selected and followed for a mean period of 18 ± 8 months. A group of 27 healthy volunteers were also investigated. One patient was excluded from the analysis since he died before completing the intestinal permeability test. Intestinal permeability was evaluated with the sugar probe drink test. It consists in the urinary recovery of previously ingested sugar probes: mannitol, a monosaccharide, and lactulose, a disaccharide. Results Patient's mean age was 53.4 ± 10.4 years, and 31(63%) were male. Differential urinary excretion of lactulose/mannitol ratio did not differ significantly between healthy controls and CCC patients, regardless of clinical signs of venous congestion, haemodynamic parameters, and severity of presentation and outcome. Conclusions The present study could not show a disturbance of the intestinal barrier in CCC patients with LVEF

Background: Sepsis is a significant contributor to organ function damage or failure that results in intestinal dysfunction. Emodin (Emo) has received much attention for its notable anti‐inflammatory and antibacterial properties. We aimed to explore the function of Emo on sepsis. Methods: Sprague Dawley (SD) rats were pretreated with 20 or 40 mg/kg of Emo, followed by using cecal ligation and perforation to establish sepsis models. Hereafter, blood glucose levels, biochemical parameters, and inflammatory cytokines were measured. Additionally, ileal myeloperoxidase (MPO) activity was also measured. Diamine oxidase (DAO) level in plasma, fluorescein isothiocyanate‐dextran 40 (FD‐40) level in serum, bacteria number in blood and peritoneal fluid, histopathological changes of ileum, and tight junction (TJ) protein expressions in ileum were tested to evaluate the barrier function. Furthermore, CD4+ and CD8+ T cells' percentages were evaluated by flow cytometry. Finally, rats' survival rate was calculated as live rats divided by the total number of rats. Results: Emo pretreatment not only decreased blood glucose level, but also downregulated triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (SCr), blood urea nitrogen (BUN) contents for sepsis rats, especially for the high dose of Emo (p <.05). Furthermore, Emo inhibited MPO activity and inflammatory factor release (p <.05). Crucially, after Emo administration, the barrier function of ileum was enhanced, evidenced by the reduced DAO, FD‐40 levels, decreased bacteria number, alleviated pathological damage in ileum and increased TJ protein expressions (p <.05). Rats treated with Emo exhibited increased percentages of CD8+ and CD4+ T cells (p <.05), as well as an improved survival rate. Conclusion: Emo exhibited a remarkable ability to attenuate sepsis by restoring intestinal dysfunction and improving survival rates, and the mechanism was closely related to anti‐inflammatory properties, which provided new solid evidence for the use of Emo in treating sepsis. [ABSTRACT FROM AUTHOR]

Aims: We analysed intestinal permeability in patients with chronic Chagas cardiomyopathy (CCC) and evaluated its association with clinical manifestations, haemodynamic parameters measured by echocardiogram, and disease outcome. Intestinal permeability was compared between CCC patients and a group of healthy controls. Background: Intestinal dysfunction may contribute to a more severe disease presentation with worse outcome in patients with CCC and heart failure. Methods: Fifty patients with CCC and left ventricular ejection fraction (LVEF) of less than 55% were prospectively selected and followed for a mean period of 18 ± 8 months. A group of 27 healthy volunteers were also investigated. One patient was excluded from the analysis since he died before completing the intestinal permeability test. Intestinal permeability was evaluated with the sugar probe drink test. It consists in the urinary recovery of previously ingested sugar probes: mannitol, a monosaccharide, and lactulose, a disaccharide. Results: Patient's mean age was 53.4 ± 10.4 years, and 31(63%) were male. Differential urinary excretion of lactulose/mannitol ratio did not differ significantly between healthy controls and CCC patients, regardless of clinical signs of venous congestion, haemodynamic parameters, and severity of presentation and outcome. Conclusions: The present study could not show a disturbance of the intestinal barrier in CCC patients with LVEF <55%, measured by lactulose/mannitol urinary excretion ratio. Further investigations are needed to verify if in patients with LVEF <40% intestinal permeability is increased. [ABSTRACT FROM AUTHOR]

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Magnolia officinalis Rehder & E.H. Wilson is traditionally used in the treatment of gastrointestinal disorders, diarrhea, and cough. Its main active ingredient, magnolol, exhibits protective effects on the lungs and gastrointestinal tract, including the inhibition of inflammation in these organs. This work aims to explore the molecular mechanism by which magnolol suppressed Chronic obstructive pulmonary disease (COPD) intestinal damage by improving the intestinal epithelial barrier. The study focused on investigating the mitigation effect of magnolol on intestinal injury and epithelial barrier in a COPD rat. Caco-2 cells were induced with TNF-α or IL-1β to establish the barrier injury model in order to explore the direct protective effect of magnolol on the intestinal barrier and elucidate the molecular mechanism by which it activates peroxisome proliferators-activated receptors-γ (PPARγ). Magnolol significantly improves pulmonary function and tissue damage in COPD rats by inhibiting inflammation, protease imbalance, and oxidative stress. It also suppresses colon tissue damage and inflammation, and protects colon epithelial barrier function by suppressing the decline of tight junction proteins, reducing colon epithelial permeability. In Caco-2 cells, magnolol directly reduces monolayer permeability, increases TEER, and upregulates tight junction protein expression induced by TNF-α or IL-1β. Drug Affinity Responsive Target Stability (DARTS) and thermal shift assays show that magnolol effectively binds to SRC, activating PPARγ signaling in Caco-2 cells and colon tissues of COPD rats. Furthermore, magnolol enhances the binding of PPARγ and RXRα, promoting their activation and entry into the nucleus. The PPARγ inhibitor GW9662 can reverse the effects of magnolol on PPARγ activation and tight junction protein upregulation in IL-1β or TNF-α induced Caco-2 cells. This work demonstrates that magnolol enhances lung and intestinal functions in COPD rats, and elucidates its mechanism of action in protecting the intestinal epithelial barrier by activating PPARγ. [Display omitted] [ABSTRACT FROM AUTHOR]

• IUGR neonates show unique gut dysfunction linked to metabolism. • Pentose phosphate pathway disruption linked to intestinal issues in IUGR. • Early biomarkers of IUGR intestinal issues identified through metabolomics. This study aimed to identify metabolic alterations in the small intestine of newborn rats with intrauterine growth restriction (IUGR), a condition linked to intestinal dysfunction. Pregnant Sprague Dawley rats underwent bilateral uterine artery ligation on gestational day 17 to induce intrauterine growth restriction or sham surgery. Rat pups were delivered spontaneously on gestational day 22. Small intestine tissues were collected on postnatal days 0 and 7 from offspring. Liquid chromatography-mass spectrometry analysis was performed to investigate untargeted metabolomic profiles. Western blot analysis assessed protein expression of key regulators. Newborn rats with intrauterine growth restriction exhibited distinct small intestine metabolic profiles compared to controls on postnatal day 0. Notably, significant alterations were observed in purine metabolism, the pentose phosphate pathway, and related pathways. Western blot analysis revealed a decrease expression in transketolase, a key enzyme of the pentose phosphate pathway, suggesting impaired activity of the pentose phosphate pathway. Additionally, decreased expression of tight junction proteins ZO-1 and occludin indicated compromised intestinal barrier function in rats with intrauterine growth restriction. Similar metabolic disruptions persisted on postnatal day 7, with further reductions in tricarboxylic acid cycle intermediates and folate biosynthesis precursors. Interestingly, lysyl-glycine, a protein synthesis marker, was elevated in rats with intrauterine growth restriction. Our findings reveal a distinct metabolic signature in the small intestine of neonatal rats with intrauterine growth restriction, characterized by disruptions in the pentose phosphate pathway, purine metabolism, and energy production pathways. These novel insights suggest potential mechanisms underlying IUGR-associated intestinal dysfunction and impaired growth. [ABSTRACT FROM AUTHOR]

Objective To observe differential peptidomics of intestinal tissues in mice with sepsisinduced intestinal dysfunction，and to investigate the mechanism of sepsis-induced intestinal dysfunction. Methods The mice model of sepsis-induced intestinal dysfunction was established by cecal ligation and perforation and divided into sham operation group（3 mice）and sepsis group（3 mice）. The peptidomic profiling of intestinal tissue was detected by liquid chromatography-tandem mass spectrometry，and the differentially expressed endogenous peptides were subjected to bioinformatics analysis to assess their possible roles in sepsis-induced intestinal dysfunction. Results A total of 458 peptides and 129 precursor proteins were identified，and 110 of them were differentially expressed，including 101 upregulated peptides and 9 downregulated peptides. Differential endogenous peptides may be involved in the occurrence and development of sepsis-induced intestinal dysfunction through regulation of metabolic pathways，antigen processing and presentation，oxidative phosphorylation，MAPK signaling pathway，cell apoptosis，etc. And 15 endogenous peptides related to sepsis-induced intestinal dysfunction were predicted. Conclusion We found 15 differentially expressed endogenous peptides，which may be the key bioactive peptides involved in sepsis-induced intestinal dysfunction. This study provides a new direction for the prevention and treatment of intestinal dysfunction in sepsis. [ABSTRACT FROM AUTHOR]

Background: One of the most common types of neurodegenerative diseases (NDDs) is Lewy body disease (LBD), which is characterized by excessive accumulation of α-synuclein (α-syn) in the neurons and affects around 6 million individuals globally. In recent years, due to the environmental factors that can affect the development of this condition, such as exposure to herbicides and pesticides, so it has become a younger disease. Currently, the vast majority of studies on the neurotoxic effects of paraquat (PQ) focus on the late mechanisms of neuronal-glial network regulation, and little is known about the early origins of this environmental factor leading to LBD. Objective: To observe the effect of PQ exposure on intestinal function and to explore the key components of communicating the gut-brain axis by establishing a mouse model. Methods and results: In this study, C57BL/6J mice were treated by intraperitoneal injection of 15 mg/kg PQ to construct an LBD time-series model, and confirmed by neurobehavioral testing and pathological examination. After PQ exposure, on the one hand, we found that fecal particle counts and moisture content were abnormal. on the other hand, we found that the expression levels of colonic tight junction proteins decreased, the expression levels of inflammatory markers increased, and the diversity and abundance of gut microbiota altered. In addition, pathological aggregation of α-syn was consistent in the colon and midbrain, and the metabolism and utilization of short-chain fatty acids (SCFAs) were also markedly altered. This suggests that pathological α-syn and SCFAs form the gut may be key components of the communicating gut-brain axis. Conclusion: In this PQ-induced mouse model, gut microbiota disruption, intestinal epithelial barrier damage, and inflammatory responses may be the main causes of gut dysfunction, and pathological α-syn and SCFAs in the gut may be key components of the communicating gut-brain axis.

PurposeRadical surgery is the most effective treatment for Hirschsprung's disease. However, some children still have symptoms of intestinal dysfunction such as constipation, abdominal distension, and recurrent enterocolitis after operation. The purpose of this study was to evaluate treatment outcomes of postoperative intestinal dysfunction in children with Hirschsprung's disease by using the principle of “anorectal balance”.MethodsThe clinical data of postoperative intestinal dysfunction in children with Hirschsprung's disease in the single treatment group from July 2019 to July 2021 were retrospectively analyzed. All the enrolled children underwent botulinum toxin injection (2.5 U/kg); 3 to 6 months later, the injection was performed again; the children who had received more than two botulinum toxin injections underwent the internal sphincter myectomy. Anorectal manometry was performed routinely after operation, and abdominal distension and defecation were recorded.ResultsA total of thirty children with postoperative intestinal dysfunction underwent radical surgery for Hirschsprung's disease were included in this study. Symptoms of constipation, abdominal distension and enterocolitis were improved after botulinum toxin injections in most children compared to before surgery (P

The limbic system plays a pivotal role in stress-induced anxiety and intestinal disorders, but how the functional circuits between nuclei within the limbic system are engaged in the processing is still unclear. In our study, the results of fluorescence gold retrograde tracing and fluorescence immunohistochemistry showed that the melanin-concentrating hormone (MCH) neurons of the lateral hypothalamic area (LHA) projected to the basolateral amygdala (BLA). Both chemogenetic activation of MCH neurons and microinjection of MCH into the BLA induced anxiety disorder in mice, which were reversed by intra-BLA microinjection of MCH receptor 1 (MCHR1) blocker SNAP-94847. In the chronic acute combining stress (CACS) stimulated mice, SNAP94847 administrated in the BLA ameliorated anxiety-like behaviors and improved intestinal dysfunction via reducing intestinal permeability and inflammation. In conclusion, MCHergic circuit from the LHA to the BLA participates in the regulation of anxiety-like behavior in mice, and this neural pathway is related to the intestinal dysfunction in CACS mice by regulating intestinal permeability and inflammation. [ABSTRACT FROM AUTHOR]

Emerging evidences demonstrate the involvement of gut microbiota in the progression of chronic kidney disease (CKD) and CKD-associated complications including cardiovascular disease (CVD) and intestinal dysfunction. In this review, we discuss the interactions between the gut, kidney and heart in CKD state, and elucidate the significant role of intestinal microbiota in the gut-kidney-heart axis hypothesis for the pathophysiological mechanisms of these diseases, during which process mitochondria may serve as a potential therapeutic target. Dysregulation of this axis will lead to a vicious circle, contributing to CKD progression. Recent studies suggest novel therapies targeting gut microbiota in the gut-kidney-heart axis, including dietary intervention, probiotics, prebiotics, genetically engineered bacteria, fecal microbiota transplantation, bacterial metabolites modulation, antibiotics, conventional drugs and traditional Chinese medicine. Further, the identification of specific microbial communities and their corresponding pathophysiological metabolites and the illumination of the gut-kidney-heart axis may contribute to innovative basic research, clinical trials and therapeutic strategies against CKD progression and uremic complications in CKD patients. [ABSTRACT FROM AUTHOR]

Introduction: The high-fructose diet in rats has been reported to cause metabolic disorders such as impaired fasting glucose levels, in-sulin resistance, dyslipidemia, and dysregulation of the renin-angiotensin system. This could lead to further complications, for instance, to the smooth muscle dysfunction.Aim: The present study aimed at developing fructose-induced metabolic perturbations in rats and the investigation of their impact on angiotensin II-induced smooth muscle intestinal motility. Materials and methods: Mature Wistar rats were randomly divided into two groups (9 rats per group): control group (drinking tap water) and fructose-drinking group (15% fructose, dissolved in tap water). At the end of the experimental period (11 weeks), the plasma levels of insulin, renin, angiotensin II and creatinine, as well as the lipid profile were assessed. Morphometric analysis and lipid index calculation were also performed. The contractile properties of ileum, colon and rectum were studied using stimulation with angiotensin II in the isolated tissue bath system. Results: Our experiment showed that drinking 15% fructose solution induced dyslipidaemia accompanied by elevated lipid indexes as well as an increase in creatinine and renin plasma levels in the rats. Conclusions: Fructose drinking and consequently the developed metabolic disorders modified the Ang II-induced intestinal activity causing a gradual alteration in the distal direction with the rectum being the most strongly affected organ.

Abstract Background Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease affecting the CNS. Recent studies have indicated that intestinal alterations play key pathogenic roles in the development of autoimmune diseases, including MS. The triterpene oleanolic acid (OA), due to its anti-inflammatory properties, has shown to beneficially influence the severity of the experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS. We herein investigate EAE-associated gut intestinal dysfunction and the effect of OA treatment. Methods Mice with MOG35–55-induced EAE were treated with OA or vehicle from immunization day and were daily analyzed for clinical deficit. We performed molecular and histological analysis in serum and intestinal tissues to measure oxidative and inflammatory responses. We used Caco-2 and HT29-MTX-E12 cells to elucidate OA in vitro effects. Results We found that OA protected from EAE-induced changes in intestinal permeability and preserved the mucin-containing goblet cells along the intestinal tract. Serum levels of the markers for intestinal barrier damage iFABP and monocyte activation sCD14 were consistently and significantly reduced in OA-treated EAE mice. Beneficial OA effects also included a decrease of pro-inflammatory mediators both in serum and colonic tissue of treated-EAE mice. Moreover, the levels of some immunoregulatory cytokines, the neurotrophic factor GDNF, and the gastrointestinal hormone motilin were preserved in OA-treated EAE mice. Regarding oxidative stress, OA treatment prevented lipid peroxidation and superoxide anion accumulation in intestinal tissue, while inducing the expression of the ROS scavenger Sestrin-3. Furthermore, short-chain fatty acids (SCFA) quantification in the cecal content showed that OA reduced the high iso-valeric acid concentrations detected in EAE-mice. Lastly, using in vitro cell models which mimic the intestinal epithelium, we verified that OA protected against intestinal barrier dysfunction induced by injurious agents produced in both EAE and MS. Conclusion These findings reveal that OA ameliorates the gut dysfunction found in EAE mice. OA normalizes the levels of gut mucosal dysfunction markers, as well as the pro- and anti-inflammatory immune bias during EAE, thus reinforcing the idea that OA is a beneficial compound for treating EAE and suggesting that OA may be an interesting candidate to be explored for the treatment of human MS.

Emerging evidences demonstrate the involvement of gut microbiota in the progression of chronic kidney disease (CKD) and CKD-associated complications including cardiovascular disease (CVD) and intestinal dysfunction. In this review, we discuss the interactions between the gut, kidney and heart in CKD state, and elucidate the significant role of intestinal microbiota in the gut-kidney-heart axis hypothesis for the pathophysiological mechanisms of these diseases, during which process mitochondria may serve as a potential therapeutic target. Dysregulation of this axis will lead to a vicious circle, contributing to CKD progression. Recent studies suggest novel therapies targeting gut microbiota in the gut-kidney-heart axis, including dietary intervention, probiotics, prebiotics, genetically engineered bacteria, fecal microbiota transplantation, bacterial metabolites modulation, antibiotics, conventional drugs and traditional Chinese medicine. Further, the identification of specific microbial communities and their corresponding pathophysiological metabolites and the illumination of the gut-kidney-heart axis may contribute to innovative basic research, clinical trials and therapeutic strategies against CKD progression and uremic complications in CKD patients.

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Aim.To determine approaches of the exacerbations treatment of chronic pancreatitis (CP) with IBS (irritable bowel syndrome)-like syndrome. Materials and methods.312 patients with exacerbation of CP were observed and received standard therapy: antispasmodics, enzymes, proton pump inhibitors. 85 (27.2%) patients had no response to treatment. After excluding obstructive CP, celiac disease, decompensation of diabetes (DD), ischemic and microscopic colitis, small intestinal bacterial overgrowth (SIBO) as a cause of abdominal pain and intestinal dysfunction, a group of 54 patients with exacerbation of CP and IBS-like syndrome was isolated. They were divided into 2 groups: group 1 persons receiving with standard treatment of CP ciprofloxacin in a dose of 500 mg 2 times a day for 10 days (26 patients), group 2 rifaximin 400 mg 3 times a day for 10 days (28 patients). The dynamics of clinical picture, biocenosis indices, endoscopic, morphological features of the colon, interleukin-2 (IL-2), IL-6, IL-8 concentration in the colon mucosa (CA) were evaluated. Results.IBS-like syndrome was determined in 54 (63.5%) patients with prolonged (more than 4 weeks) exacerbation of CP. A modification of therapy is proposed with the results of clinical and instrumental, laboratory, bacteriological studies. 68% of patients with exacerbation of CP, receiving in addition to the standard regimen rifaximin, achieved clinical improvement, normalization of intestinal biocenosis, reduced concentrations of cytokines in tissues, reducing signs of chronic inflammation in the colon mucosa with reducing concentrations of IL-2, IL-6, IL-8 in colon mucosa (p0.05). Conclusion.Exacerbation of CP, resistant to standard therapy, may be associated with the formation of IBS-like syndrome. The inclusion of rifaximin in the complex therapy of prolonged exacerbation of CP contributes to the relief of intestinal dysfunction, abdominal pain of intestine, improves biocenosis, reduces inflammatory modifications, and reduces the concentration of cytokines in the colon mucosa.

Adult intussusception during the perioperative period is defined as an extremely rare condition, especially when it emerges within short intervals of laparotomy, which may be explained as an unphysiological peristaltic function of the bowel without any lead points. Accurate diagnosis and therapeutic schedule predict a satisfactory outcome. Here, we introduce the case of a 32-year-old man who had symptoms of abdominal pain, no gas emission, and defecation shortly after liver transplantation. Intussusception was definitely diagnosed by abdominal CT, and then reduction was operated successfully by three-dimensional laparoscopy-assisted operation. There were no other complaints, and no secondary lesions were detected during the postoperative rehabilitation process in the hospital and over a follow-up period of 6 months. Relevant literature has been summarized subsequently. A promising minimally invasive surgery along with minimal secondary trauma was presented by laparoscopy in this rare case, providing the potential remedy for perioperative intussusception in the adult.

In the current study, we sought to determine the roles of histone deacetylase 5 (HDAC5) on the promotion of intestinal sepsis in a mouse model. Dual luciferase reporter gene assay was used to determine the binding relationship between HDAC5 and Ghrelin. Cecal ligation and puncture (CLP) was used as an animal model of intestinal sepsis. The roles of HDAC5 on intestinal sepsis were determined by HDAC5 knockdown, overexpression, and inhibitor (LMK-235) in vivo. Mice intestinal permeability and intestinal epithelial damage were evaluated, and HE staining was used to evaluate the intestinal mucosal injury index. Lipopolysaccharide (LPS)-treated intestinal-derived macrophages served as a cell model of sepsis, followed by the loss-of-function and gain-of-function assays. ELISA was used to determine the levels of inflammatory factors, and TUNEL staining was used to detect intestinal cell apoptosis. HDAC5 was upregulated in the intestine of sepsis patients. This increased HDAC5 expression was positively correlated with the expression of inflammatory factors TNF-a, IL-1ß, IL-6, and HMGB1, as well as the intestinal dysfunction-related factors IFABP. In sepsis mice, the expression of inflammatory factors was reduced by HDAC5 knockdown. HDAC5 knockdown also improved survival, morphology of intestinal tissue, intestinal permeability, and epithelial damage. Ghrelin was bound and inhibited by HDAC5, but E2F1 expression was increased by Ghrelin overexpression, leading to inhibition of the NF-κB pathway. Ghrelin and E2F1 expression were increased by the treatment with HDAC5 inhibitor LMK-235, which inhibited the NF-κB pathway to improve intestinal dysfunction in the sepsis model. In conclusion, HDAC5 inhibits Ghrelin to reduce E2F1 and thus activate the NF-κB pathway, thereby promoting intestinal sepsis. [ABSTRACT FROM AUTHOR]

Hyperbaric oxygen (HBO) therapy can attenuate neurological impairment after traumatic brain injury (TBI) and alleviate intestinal dysfunction. However, the role and mechanism of HBO therapy in intestinal dysfunction following TBI remain unclear. Herein, by establishing a mouse model of controlled cortical impact (CCI), we found that HBO therapy reduced histopathological lesions and decreased the levels of inflammatory and oedema proteins in the intestinal tissues of mice 10 days after TBI. We also showed that HBO therapy improved microbiome abundance and probiotic (particularly g&#95;Bifidobacterium ) colonisation in mice post-CCI. Then, we identified that the m 6 A level imcreased notably in injured cortical tissue of CCI+HBO group compared with the CCI group following CCI. Thus, our results suggested that HBO therapy could alleviate TBI-induced intestinal dysfunction and m 6 A might participate in this regulation process, which provides new insights for exploring the specific mechanism and targets of HBO in the treatment of intestinal dysfunction after TBI, thereby improving the therapeutic effect of HBO., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Impaired intestinal function is frequently detected in newborns with intrauterine growth restriction (IUGR), whereas the mechanism between transcriptome profiles and small intestinal dysfunction is still unclear. Therefore, this study was conducted by using IUGR neonatal piglets to uncover the mechanism underlying intestinal dysfunction. Neonatal piglets with IUGR and normal birth weight (NBW) were sacrificed at birth. Transcriptomic sequencing was performed on jejunum samples and generated 18,997 and 17,531 genes in NBW and IUGR groups, respectively. A total of 10 differentially expressed genes (DEGs) were identified; of note, only seven were mapped to the genome reference database, with two up-regulated (HSF4 and NR1H4; heat shock transcription factor 4 and nuclear receptor subfamily 1 group H member 4, respectively) and five down-regulated (SLC35C1, BTNL3, BPI, NLRP6, and SLC5A8; Solute carrier family 35 member C1, butyrophilin like 3, bactericidal permeability increasing protein, NLR family pyrin domain containing 6, and solute carrier family 5 member 8, respectively). Combining an enrichment analysis and reverse transcriptase–quantitative polymerase chain reaction validation of DEGs, our results proved the lipid metabolism disorder, intestinal dysfunction, and inflammatory response in IUGR piglets. Here, IUGR piglets presented lower concentration of glucose and triglyceride and higher concentration of total cholesterol and low-density lipoprotein cholesterol in plasma, compared with NBW piglets. Histological analysis revealed decreased mucins and increased apoptosis in both jejunum and ileum for IUGR piglets. Collectively, we found that IUGR induced intestinal dysfunction by altering lipid metabolism, intestinal barrier, and inflammatory response in neonatal piglets at birth, which provides new insights into the prevention and treatment of IUGR that protects against metabolic disorders and inflammatory-related diseases.

Traumatic brain injuries (TBI) and its sequelae are becoming one of the most pressing public health concerns worldwide. It is one of the leading causes of increased morbidity and mortality. The primary insult to the brain can cause ischemic brain injury, paralysis, concussions, death, and other serious complications. Brain injury also involves other systems through a secondary pathway resulting in multiple complications during and after hospitalization. The focus of our article is to assess the literature available on traumatic brain injury and intestinal dysfunctional to highlight the aspects of epidemiology, pathophysiology, and different diagnostic approaches for early diagnosis of gut dysfunction. We review studies done in both humans and animals, to better understand this underrated topic, as it costs billions of dollars to the healthcare industry because of delayed diagnosis. [ABSTRACT FROM AUTHOR]

Impaired intestinal function is frequently detected in newborns with intrauterine growth restriction (IUGR), whereas the mechanism between transcriptome profiles and small intestinal dysfunction is still unclear. Therefore, this study was conducted by using IUGR neonatal piglets to uncover the mechanism underlying intestinal dysfunction. Neonatal piglets with IUGR and normal birth weight (NBW) were sacrificed at birth. Transcriptomic sequencing was performed on jejunum samples and generated 18,997 and 17,531 genes in NBW and IUGR groups, respectively. A total of 10 differentially expressed genes (DEGs) were identified; of note, only seven were mapped to the genome reference database, with two up-regulated (HSF4 and NR1H4 ; heat shock transcription factor 4 and nuclear receptor subfamily 1 group H member 4, respectively) and five down-regulated (SLC35C1 , BTNL3 , BPI , NLRP6 , and SLC5A8 ; Solute carrier family 35 member C1, butyrophilin like 3, bactericidal permeability increasing protein, NLR family pyrin domain containing 6, and solute carrier family 5 member 8, respectively). Combining an enrichment analysis and reverse transcriptase–quantitative polymerase chain reaction validation of DEGs, our results proved the lipid metabolism disorder, intestinal dysfunction, and inflammatory response in IUGR piglets. Here, IUGR piglets presented lower concentration of glucose and triglyceride and higher concentration of total cholesterol and low-density lipoprotein cholesterol in plasma, compared with NBW piglets. Histological analysis revealed decreased mucins and increased apoptosis in both jejunum and ileum for IUGR piglets. Collectively, we found that IUGR induced intestinal dysfunction by altering lipid metabolism, intestinal barrier, and inflammatory response in neonatal piglets at birth, which provides new insights into the prevention and treatment of IUGR that protects against metabolic disorders and inflammatory-related diseases. [ABSTRACT FROM AUTHOR]

Being a hydroxylated metabolite of aflatoxin B1 (AFB1) and the most threatening aspect of AFB1 contamination, aflatoxin M1 (AFM1) can lead to hepatotoxicity and hepato-carcinogenicity, and possess intestinal cytotoxicity. However, little is known about the potential mechanisms of the extrahepatic effect. The aim of this study was to investigate intestinal dysfunction induced by AFM1 via transcriptome analysis. Gene expression profiling was analyzed to comparatively characterize the differentially expressed genes (DEGs) after differentiated Caco-2 cells were exposed to different concentrations of AFM1 for 48 h. A total of 165 DEGs were significantly clustered into two down-regulated patterns. Protein-protein interaction (PPI) network analysis based on Search Tool for Retrieval of Interacting Genes (STRING)suggested that 23 key enzymes mainly participated in the regulation of the cell cycle. Q-PCR analysis was performed to validate that key 12 genes (BUB1 , BUB1B , MAD2L1 , CCNA2 , RB1 , CDK1 , ANAPC4 , ATM , KITLG , PRKAA2 , SIRT1 , and SOS1) were involved. This study firstly revealed that the toxicity of AFM1 to intestinal functions may be partly due to the occurrence of cell cycle arrest, which is linked to changes in CDK1, SOS1/Akt, and AMPK signaling molecules. • Transcriptomic study and trend analysis were performed to observe the dose-dependent effects on global gene profiles in differentiated Caco-2 cells after 48 h of exposure to AFM1. • STRING was used to construct PPI network to reveal that 23 genes were identified clustered into the key pathway cell cycle; and flow cytometry analysis indicated that AFM1 could evoke S-phase cell cycle arrest. • CDK1, SOS1/Akt, and AMPK signaling molecules were involved in the biological process. [ABSTRACT FROM AUTHOR]

We have previously shown that diarrheagenic Escherichia coli (DEC) and non-DEC are prevalent in food sources and irrigation water in South Africa. Recent data suggest that an increased relative abundance of faecal Enterobacteriaceae is associated with poorer health outcomes among children in developing countries. Thus, exposure to non-DEC from environmental sources may incur adverse effects, although the mechanisms underlying these effects remain obscure. To further elucidate this phenomenon, we assayed non-DEC strains from environmental sources in South Africa for phenotypes that may be associated with intestinal dysfunction (ID). DEC strains were also used. The strains had previously been isolated from Producer Distributor Bulk Milk (PDBM), irrigated lettuce, street vendor coleslaw and irrigation water. In-vitro assays identified; biofilm formation (n = 38), extracellular polymeric substance (EPS) formation (n = 38), cytotoxic activity (n = 10), disruption of tight junctions and induction of Interleukin 8 (IL-8) on polarized T-84 cells (n = 20). The number of strains tested for each assay differed, depending on prior molecular and phenotypic characterization that signalled potential pathogenicity in-vitro. Subsequently, all strains having data points for all analyses were used to compute Principal Component Analysis (PCA) plot curves to infer potential associations amongst test strains and a standard DEC pathogenic strain (042). Biofilm formation on glass coverslips after strains were grown in nutrient-rich media (LB and DMEM-F12 + 0.5% D-Mannose) at 37 °C varied based on pathotype (DEC and non-DEC) and source of isolation (food, irrigation water, clinical) suggesting that pathotype and source isolation influence persistence within a defined environmental niche. Additionally, DEC isolated from irrigated lettuce had a significantly higher (p ≤ 0.05) propensity for biofilm formation in both media compared to all strains including DEC standard controls. This suggested the propensity for irrigated lettuce as a potential source of persistent pathogenic strains. Furthermore, all strains were able to form EPS suggesting the ability to form mature biofilms under conditions relevant for food processing (20–25 °C). Of the (60%, 6 out of 10) strains that showed cytotoxic activity, most (83%, 5 out of 6 strains) were non-DEC isolated from food sources many of which are consumed with minimal processing. Mean percentage reduction in initial TEER (a measure of intestinal disruption), did not significantly differ (p = 0.05) in all test strains from that observed in the standard DEC. Additionally, IL-8 induction from strains isolated from PDBM (139 pg/mL), irrigation water (231.93 pg/mL) and irrigated lettuce (152.98 pg/mL) was significantly higher (p ≤ 0.05) than in the commensal strain aafa. PCA categorized strains based on sources of isolation showed potential for use in source tracking especially when comparing many strains from various environmental sources. We show that non-DEC strains along the food chain possess characteristics that may lead to ID. Further investigations using a larger collection of strains may provide a clearer link to these reported observations that could be associated with the high diarrheal disease burden within the country, especially among infants. Image 1 • Non-DEC formed biofilms, cytotoxins, disrupted epithelial cells and induced interleukin-8. • Epithelial cell disruption was comparable to a standard DEC strain EAEC 042. • PCA clustered strains based on isolation source showing potential use in source tracking. • Further studies with more strains required to provide clearer link of Non-DEC in causing ID. [ABSTRACT FROM AUTHOR]

Highlights from the article: (C) Statistical graph of Nrf2 and GAPDH protein in the different groups. (H, I) Statistical graph of NF- B, I B, and GAPDH protein in the different groups. (C) Statistical graph of Nrf2 and GAPDH protein in the different groups.

Severe acute pancreatitis (SAP) is a digestive system disease that is associated with a range of complications including intestinal dysfunction. In this study, we determined that the chalcone compound, isoliquiritigenin (ISL), reduces pancreatic and intestinal injury in a mouse model of SAP. These effects were achieved by suppressing oxidative stress and the inflammatory responses to SAP. This was evidenced by a reduction in histological score, and malondialdehyde (MDA), interleukin (IL)-6, tumor necrosis factor (TNF)-α and cleaved-caspase-3 (c-caspase-3) protein along with an increase in Nrf2, hemeoxygenase-1 (HO-1), quinone oxidoreductase 1 (NQO1), and superoxide dismutase (SOD). We then used Nrf2-/- mice to test the protective effect of Nrf2 during ISL treatment of SAP. Our results indicated that Nrf2-/- mice had greater pancreatic injury and intestinal dysfunction than wild-type mice. They also had reduced adherens junctions (P120-catenin) and tight junctions (occludin), and increased activated nuclear factor-κB (NF-κB) protein. In Nrf2-/- mice, ISL was less effective at these functions than in the WT mice. In conclusion, this study demonstrated that ISL exerts its protective effects against oxidative stress and inflammatory injury after SAP via regulation of the Nrf2/NF-κB pathway. It also showed that the efficacy of ISL in repairing the intestinal barrier damage caused by SAP is closely related to the Nrf2 protein. Our findings demonstrated that Nrf2 is an important protective factor against SAP-induced injuries in the pancreas and intestines.

Intestinal dysfunction and microbiome changes are actively discussed in the modern literature as the most important link in the development of neurodegenerative changes in Parkinson's disease. The article discusses the pathogenetic chain «microbiome- intestine-brain», as well as factors that affect the development of intestinal dysbiosis. A promising direction for influencing microflora and inflammatory changes in the intestine is the use of polyphenols, primarily curcumin. The review of experimental, laboratory, clinical research proving the pleiotropic effect of curcumin, including its antioxidant, anti-inflammatory, neuroprotective effects, realized both through peripheral and central mechanisms is presented.

Severe acute pancreatitis (SAP) is a digestive system disease that is associated with a range of complications including intestinal dysfunction. In this study, we determined that the chalcone compound, isoliquiritigenin (ISL), reduces pancreatic and intestinal injury in a mouse model of SAP. These effects were achieved by suppressing oxidative stress and the inflammatory responses to SAP. This was evidenced by a reduction in histological score, and malondialdehyde (MDA), interleukin (IL)-6, tumor necrosis factor (TNF)-α and cleaved-caspase-3 (c-caspase-3) protein along with an increase in Nrf2, hemeoxygenase-1 (HO-1), quinone oxidoreductase 1 (NQO1), and superoxide dismutase (SOD). We then used Nrf2-/- mice to test the protective effect of Nrf2 during ISL treatment of SAP. Our results indicated that Nrf2-/- mice had greater pancreatic injury and intestinal dysfunction than wild-type mice. They also had reduced adherens junctions (P120-catenin) and tight junctions (occludin), and increased activated nuclear factor-κB (NF-κB) protein. In Nrf2-/- mice, ISL was less effective at these functions than in the WT mice. In conclusion, this study demonstrated that ISL exerts its protective effects against oxidative stress and inflammatory injury after SAP via regulation of the Nrf2/NF-κB pathway. It also showed that the efficacy of ISL in repairing the intestinal barrier damage caused by SAP is closely related to the Nrf2 protein. Our findings demonstrated that Nrf2 is an important protective factor against SAP-induced injuries in the pancreas and intestines. [ABSTRACT FROM AUTHOR]

As head injuries and their sequelae have become an increasingly salient matter of public health, experts in the field have made great progress elucidating the biological processes occurring within the brain at the moment of injury and throughout the recovery thereafter. Given the extraordinary rate at which our collective knowledge of neurotrauma has grown, new insights may be revealed by examining the existing literature across disciplines with a new perspective. This article will aim to expand the scope of this rapidly evolving field of research beyond the confines of the central nervous system (CNS). Specifically, we will examine the extent to which the bidirectional influence of the gut-brain axis modulates the complex biological processes occurring at the time of traumatic brain injury (TBI) and over the days, months, and years that follow. In addition to local enteric signals originating in the gut, it is well accepted that gastrointestinal (GI) physiology is highly regulated by innervation from the CNS. Conversely, emerging data suggests that the function and health of the CNS is modulated by the interaction between 1) neurotransmitters, immune signaling, hormones, and neuropeptides produced in the gut, 2) the composition of the gut microbiota, and 3) integrity of the intestinal wall serving as a barrier to the external environment. Specific to TBI, existing pre-clinical data indicates that head injuries can cause structural and functional damage to the GI tract, but research directly investigating the neuronal consequences of this intestinal damage is lacking. Despite this void, the proposed mechanisms emanating from a damaged gut are closely implicated in the inflammatory processes known to promote neuropathology in the brain following TBI, which suggests the gut-brain axis may be a therapeutic target to reduce the risk of Chronic Traumatic Encephalopathy and other neurodegenerative diseases following TBI. To better appreciate how various peripheral influences are implicated in the health of the CNS following TBI, this paper will also review the secondary biological injury mechanisms and the dynamic pathophysiological response to neurotrauma. Together, this review article will attempt to connect the dots to reveal novel insights into the bidirectional influence of the gut-brain axis and propose a conceptual model relevant to the recovery from TBI and subsequent risk for future neurological conditions. [ABSTRACT FROM AUTHOR]

Sepsis is a systemic inflammatory reaction, which is aggravated by aspects of the immune response that are thought to be inhibited by Omega-3 fatty acids. The aim of the present study was to determine if Omega-3 fatty acid could modulate immunological function and improve survival rate among septic patients with intestinal dysfunction. A total of 48 mechanically ventilated patients with intestinal dysfunction were included in this prospective, randomized and single-blind clinical study. Patients were randomly divided into control (group A) and treatment groups (group B). The treatment protocol for all the participants followed the Sepsis Survival Campaign guidelines, and group B received total parenteral nutrition containing 100 ml of Omega-3 fatty acids (containing 10 g refined fish oil) per day in addition to the standard treatment applied in group A. Group B had a significantly lower mortality rate compared with group A (12.5 vs. 41.7%, P<0.05) during the 28-day follow-up. Group B also had lower Acute Physiology and Chronic Health Evaluation II scores (P<0.05) and lower Marshall scores (P<0.05) at day 7. In addition, group B had a higher ratio of T helper to inducer lymphocytes as well as a higher ratio of CD4 to CD8 lymphocytes (P<0.01 for both) than group A. It was concluded that Omega-3 fatty acids improved T helper/inducer and CD4/CD8 ratios, and may have reduced mortality, among septic patients with intestinal dysfunction. [ABSTRACT FROM AUTHOR]

Gastrointestinal dysfunction is one of several physiologic complications in patients with traumatic brain injury (TBI). TBI can result in increased intestinal permeability resulting from apoptosis of intestinal epithelial cells, which contain a large number of mitochondria for persisting barrier function. Autophagy of damaged mitochondria (mitophagy) controls the quality of the mitochondria and regulates cellular homeostasis. However, the exact mechanism of mitophagy that underlies the pathological changes induced by TBI is unknown. Here, we report that mitophagy decreases the intestinal epithelial cell damage and apoptosis that are activated in a rat model of controlled cortical impact (CCI). CCI-induced mitophagy is associated with an increase in 3-nitrotyrosine and 4-hydroxynonenal, indicating that oxidative stress may increase in response to mitochondrial disturbance. CCI also results in the expression of the tight junction proteins zonula occludens-1 (ZO-1) and occludin, which may regulate the in vivo intestinal hyperpermeability induced by CCI. Additionally, CCI-induced mitophagy was shown to be mediated by the oxidative stress-related extracellular signal-regulated kinase (ERK)/nuclear factor-erythroid2-like2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway, which may serve to reduce the apoptosis induced by oxidative stress. These results suggest that CCI-induced mitophagy serves to diminish apoptosis-mediated intestinal epithelial cell damage and to improve intestinal permeability, via ERK/Nrf2/HO-1 signaling. These findings may be useful in the design of rational approaches for the prevention and treatment of symptoms associated with TBI. [ABSTRACT FROM AUTHOR]

Background: Small-bowel dysfunction exerts a relevant prognostic impact in the critically ill patients. Citrullinemia has been used in the evaluation of the intestinal function and it is considered an objective parameter of the functional enterocyte mass. Present study proposes to determine the intestinal dysfunction prevalence and the citrullinemia kinetic profile in severe trauma patients and to investigate its correlation with severity indicators and clinical outcome.Methods: A prospective study including 23 critical trauma patients was performed. Aminoacidemias were quantified, by ion exchange chromatography, at the admission and at the first and third days. Severity and outcome parameters were registered.Results: In severe trauma patients, severe hypocitrullinemia (< 20 μmol/L) prevalence at admission was high (69.6%) and mean citrullinemia was low (19.5 ± 11.1 μmol/L). Baseline citrullinemia was inversely and significantly correlated with shock index (r = -55.1%, p = 0.008) and extent of invasive ventilation support (r = -42.7%, p = 0.042). Citrullinemia < 13.7 μmol/L at admission, observed in 17.4% of patients, was associated with higher shock index (1.27 ± 0.10 versus 0.75 ± 0.18, p = 0.0001) and longer duration of invasive ventilation support (20.3 ± 7 versus 11.2 ± 7.1 days, p = 0.029) and intensive care unit stay (22 ± 5.9 versus 12.2 ± 8.8 days, p = 0.048). A citrullinemia decrease in the first day after admittance superior to 12.7% constituted a significant predictive factor of in-hospital mortality (75 versus 14.3%, p = 0.044; odds ratio = 7.8; accuracy = 65.2%; specificity = 92.3%; negative predictive value = 85.7%] and lower actuarial survival (69.8 ± 41.6 versus 278.1 ± 37.4 days, p = 0.034).Conclusions: Those results confirm the high prevalence and the prognostic relevance of hypocitrullinemia, considered a biomarker of enterocyte dysfunction, in severe trauma patients. [ABSTRACT FROM AUTHOR]