Gut Barrier Function

The gut-skin axis has become an important conceptual framework to identify a relationship between gut microbiota and skin immunity, particularly in autoimmune dermatologic diseases. This narrative review aims to summarize recent data examining how gut dysbiosis, characterized by low microbial diversity and disruption of each of the gut's microbial communities, plays a role in the pathogenesis and pathophysiology of psoriasis, systemic lupus erythematosus (SLE), alopecia areata, and scleroderma. We consider different pathways, including but not limited to increased intestinal permeability ("leaky gut"), Th17/Treg balance, the presence of and/or development of pro-inflammatory cytokines, and molecular mimicry, for how gut dysbiosis drives immune dysregulation in the skin. Clinical and translational evidence of microbiome-based therapies with probiotics, prebiotics, and fecal microbiota transplantation (FMT) has been shown not only to improve disease severity but also reduce systemic inflammation and restore gut microbiome diversity and community structure. Specific AMR therapies have indicated differences in PASI, SLEDAI, and inflammatory markers such as IL-6 and TNF-α. This narrative review strongly affirms that ambient need for more precision-based solutions to prevent and treat autoimmunity using a combination of multiomics, gut microbiome profiling, as well as artificial intelligence (AI)-driven individualized solutions. Ultimately, the gut-skin axis depicts autoimmune skin diseases from single dermatologic disease classifications to systemic immune diseases grounded in gut health, offering new possibilities for diagnosis, intervention, and disease modulation.

The gut microbiome plays a pivotal role in human health, yet its dynamic response to acute viral challenges remains poorly understood. Leveraging highresolution digital twin simulations powered by the Omniverse Lagrangian (L omni), we uncover a previously underappreciated symbiotic relationship where the gut microbiome adapts to enhance antiviral defense. In simulated human twins, Adam D (male, 48 years) and Eve D (female, 60 years), exposure to a novel RNA virus triggered rapid microbial shifts within 48-72 hours, increasing beneficial bacterial populations (e.g., Lactobacillus, Bifidobacterium) by 15-20% and short-chain fatty acid (SCFA) production by up to 20%. These changes strengthened gut barrier integrity, reduced inflammation (IL-6 decreased by 8-12%), and boosted T-cell activity by 20-25%, accelerating viral clearance by 30-50% compared to controls. High stress and poor diet disrupted this adaptation, highlighting the microbiome's sensitivity to host conditions. Unlike real-world studies, digital twins enable repeated experiments under identical conditions within seconds, allowing 1 precise separation of cause and effect with high confidence. Our findings reveal a deeper human-microbiome symbiosis, with significant implications for personalized antiviral strategies.

Synbiotics, the combination of probiotics and prebiotics, are known to confer health benefits via intestinal microbiota modulation. However, significant intestinal microbiota alterations can be difficult to determine in intervention studies based on solely bacterial stool metagenomic analysis. Intestinal microbiota constituents secrete 20–200-nm-sized extracellular vesicles (EVs) containing microbial DNA, proteins, and lipids that are distributed throughout the body, providing an alternative target for microbiota metagenomic analysis. Here, we determined the impact of a synbiotic beverage enriched with the kimchi-derived bacterium Leuconostoc holzapfelii (L. holzapfelii) on the intestinal microbiota and local and circulatory microbiota-derived EV composition of healthy Korean adults. We isolated microbial DNA from stool bacteria, stool EVs, and urinary EVs and conducted next-generation sequencing of the 16S rDNA V3–V4 regions before and after synbiotic consumption. The species diver...

Background: One way to improve both the ecological performance and functionality of probiotic bacteria is by combining them with a prebiotic in the form of a synbiotic. However, the degree to which such synbiotic formulations improve probiotic strain functionality in humans has not been tested systematically. Our goal was to use a randomized, double-blind, placebo-controlled, parallel-arm clinical trial in obese humans to compare the ecological and physiological impact of the prebiotic galactooligosaccharides (GOS) and the probiotic strains Bifidobacterium adolescentis IVS-1 (autochthonous and selected via in vivo selection) and Bifidobacterium lactis BB-12 (commercial probiotic allochthonous to the human gut) when used on their own or as synbiotic combinations. After 3 weeks of consumption, strain-specific quantitative real-time PCR and 16S rRNA gene sequencing were performed on fecal samples to assess changes in the microbiota. Intestinal permeability was determined by measuring s...

Alcohol binge drinking is a dangerous drinking habit, associated with neurological problems and inflammation. The impact of a single alcohol binge on innate immunity, gut barrier and gut microbiome was studied. In this cohort study 15 healthy volunteers received 2 ml vodka 40% v/v ethanol/kg body weight. Neutrophil function was studied by flow cytometry; markers of gut permeability and inflammation (lactulose/mannitol/sucrose test, zonulin, calprotectin, diamino-oxidase) were studied with NMR spectroscopy and enzyme-linked immunosorbent assay in urine, stool and serum respectively. Bacterial products in serum were quantified using different reporter cell lines. Gut microbiome composition was studied by 16S rDNA sequencing and bioinformatics analysis. After a single alcohol binge, neutrophils were transiently primed and the response to E.coli stimulation with reactive oxygen species (ROS) production was transiently increased, on the other hand the percentage of neutrophils that did not perform phagocytosis increased. No changes in gut permeability, inflammatory biomarker, bacterial translocation and microbiome composition could be detected up to 4 hours after a single alcohol binge or on the next day. A single alcohol binge in young, healthy volunteers transiently impacts on neutrophil function. Although the exact biological consequence of this finding is not clear yet, we believe that this strengthens the importance to avoid any alcohol binge drinking, even in young, otherwise healthy persons.

This study examined the effects of some dietary protein sources on intestinal barrier function in the colon of mice. 24 female ICR mice were randomly grouped into 4 groups (n=6) fed casein, soybean protein, whey protein concentrate (WPC), and egg white diet for 28 days. In this study, we collected the colon to analyzed the TJs proteins. Cecal contents were also collected to analyze the SCFAs. Mice fed with WPC showed the highest serum LBP concentration. Soybean and casein groups had the highest expression of occludin in the colon of mice. Total SCFAs were not significantly different among the groups. Correlation analysis showed that there is a positive correlation between ZO-1 and ZO-2 with total SCFAs. There is a positive correlation between plasma LBP concentration with claudin-3 expression in the colon of mice. These results confirmed that various dietary protein intake has a significant impact on the regulation of intestinal barrier integrity and SCFAs production might be contri...

Background: Environmental Enteropathy (EE), characterized by alterations in intestinal structure, function, and immune activation, is believed to be an important contributor to childhood undernutrition and its associated morbidities, including stunting. Half of all global deaths in children < 5 years are attributable to under-nutrition, making the study of EE an area of critical priority. Methods: Community based intervention study, divided into two sub-studies, 1) Longitudinal analyses and 2) Biopsy studies for identification of EE features via omics analyses. Birth cohorts in Matiari, Pakistan established: moderately or severely malnourished (weight for height Z score (WHZ) < − 2) children, and well-nourished (WHZ > 0) children. Blood, urine, and fecal samples, for evaluation of potential biomarkers, will be collected at various time points from all participants (longitudinal analyses). Participants will receive appropriate educational and nutritional interventions; non-responders will undergo further evaluation to determine eligibility for further workup, including upper gastrointestinal endoscopy. Histopathological changes in duodenal biopsies will be compared with duodenal biopsies obtained from USA controls who have celiac disease, Crohn's disease, or who were found to have normal histopathology. RNA-Seq will be employed to characterize mucosal gene expression across groups. Duodenal biopsies, luminal aspirates from the duodenum, and fecal samples will be analyzed to define microbial community composition (omic analyses). The relationship between histopathology, mucosal gene expression, and community configuration will be assessed using a variety of bioinformatic tools to gain better understanding of disease pathogenesis and to identify mechanism-based biomarkers. Ethical review committees at all collaborating institutions have approved this study. All results will be made available to the scientific community.

Background During aging, alterations of the intestinal microbial ecosystem can occur contributing to immunosenescence, inflamm-aging and impairment of intestinal barrier function (increased intestinal permeability; IP). In the context of a diet-microbiota-IP axis in older subjects, food bioactives such as polyphenols may play a beneficial modulatory role. Methods MaPLE is a project centered on a randomized, controlled cross-over dietary intervention trial [polyphenol-rich diet (PR-diet) versus control diet (C-diet)] targeted to older people (≥ 60 y) living in a well-controlled setting (i.e. nursing home). The 8-week interventions are separated by an 8-week wash-out period. Three small portions per day of selected polyphenol-rich foods are consumed during intervention in substitution of other comparable products within the C-diet. Biological samples are collected before and after each treatment period to evaluate markers related to IP, inflammation, vascular function, oxidative stres...

A major challenge in affluent societies is the increase in disorders related to gut and metabolic health. Chronic over nutrition by unhealthy foods high in energy, fat, and sugar, and low in dietary fibre is a key environmental factor responsible for this development, which may cause local and systemic inflammation. A low intake of dietary fibre is a limiting factor for maintaining a viable and diverse microbiota and production of short-chain fatty acids in the gut. A suppressed production of butyrate is crucial, as this short-chain fatty acid (SCFA) can play a key role not only in colonic health and function but also at the systemic level. At both sites, the mode of action is through mediation of signalling pathways involving nuclear NF-κB and inhibition of histone deacetylase. The intake and composition of dietary fibre modulate production of butyrate in the large intestine. While butyrate production is easily adjustable it is more variable how it influences gut barrier function and inflammatory markers in the gut and periphery. The effect of butyrate seems generally to be more consistent and positive on inflammatory markers related to the gut than on inflammatory markers in the peripheral tissue. This discrepancy may be explained by differences in butyrate concentrations in the gut compared with the much lower concentration at more remote sites.

Gut barrier function is key in maintaining a balanced response between the host and its microbiome. The microbiota can modulate changes in gut barrier as well as metabolic and inflammatory responses. This highly complex system involves numerous microbiota-derived factors. The gut symbiont Akkermansia muciniphila is positively correlated with a lean phenotype, reduced body weight gain, amelioration of metabolic responses and restoration of gut barrier function by modulation of mucus layer thickness. However, the molecular mechanisms behind its metabolic and immunological regulatory properties are unexplored. Herein, we identify a highly abundant outer membrane pili-like protein of A. muciniphila MucT that is directly involved in immune regulation and enhancement of trans-epithelial resistance. The purified Amuc_1100 protein and enrichments containing all its associated proteins induced production of specific cytokines through activation of Toll-like receptor (TLR) 2 and TLR4. This mainly leads to high levels of IL-10 similar to those induced by the other beneficial immune suppressive microorganisms such as Faecalibacterium prausnitzii A2-165 and Lactobacillus plantarum WCFS1. Together these results indicate that outer membrane protein composition and particularly the newly identified highly abundant pili-like protein Amuc_1100 of A. muciniphila are involved in host immunological homeostasis at the gut mucosa, and improvement of gut barrier function.

Background: Environmental Enteropathy (EE), characterized by alterations in intestinal structure, function, and immune activation, is believed to be an important contributor to childhood undernutrition and its associated morbidities, including stunting. Half of all global deaths in children < 5 years are attributable to under-nutrition, making the study of EE an area of critical priority. Methods: Community based intervention study, divided into two sub-studies, 1) Longitudinal analyses and 2) Biopsy studies for identification of EE features via omics analyses. Birth cohorts in Matiari, Pakistan established: moderately or severely malnourished (weight for height Z score (WHZ) < − 2) children, and well-nourished (WHZ > 0) children. Blood, urine, and fecal samples, for evaluation of potential biomarkers, will be collected at various time points from all participants (longitudinal analyses). Participants will receive appropriate educational and nutritional interventions; non-responders will undergo further evaluation to determine eligibility for further workup, including upper gastrointestinal endoscopy. Histopathological changes in duodenal biopsies will be compared with duodenal biopsies obtained from USA controls who have celiac disease, Crohn's disease, or who were found to have normal histopathology. RNA-Seq will be employed to characterize mucosal gene expression across groups. Duodenal biopsies, luminal aspirates from the duodenum, and fecal samples will be analyzed to define microbial community composition (omic analyses). The relationship between histopathology, mucosal gene expression, and community configuration will be assessed using a variety of bioinformatic tools to gain better understanding of disease pathogenesis and to identify mechanism-based biomarkers. Ethical review committees at all collaborating institutions have approved this study. All results will be made available to the scientific community.

Background: Environmental Enteropathy (EE), characterized by alterations in intestinal structure, function, and immune activation, is believed to be an important contributor to childhood undernutrition and its associated morbidities, including stunting. Half of all global deaths in children < 5 years are attributable to under-nutrition, making the study of EE an area of critical priority. Methods: Community based intervention study, divided into two sub-studies, 1) Longitudinal analyses and 2) Biopsy studies for identification of EE features via omics analyses. Birth cohorts in Matiari, Pakistan established: moderately or severely malnourished (weight for height Z score (WHZ) < − 2) children, and well-nourished (WHZ > 0) children. Blood, urine, and fecal samples, for evaluation of potential biomarkers, will be collected at various time points from all participants (longitudinal analyses). Participants will receive appropriate educational and nutritional interventions; non-responders will undergo further evaluation to determine eligibility for further workup, including upper gastrointestinal endoscopy. Histopathological changes in duodenal biopsies will be compared with duodenal biopsies obtained from USA controls who have celiac disease, Crohn's disease, or who were found to have normal histopathology. RNA-Seq will be employed to characterize mucosal gene expression across groups. Duodenal biopsies, luminal aspirates from the duodenum, and fecal samples will be analyzed to define microbial community composition (omic analyses). The relationship between histopathology, mucosal gene expression, and community configuration will be assessed using a variety of bioinformatic tools to gain better understanding of disease pathogenesis and to identify mechanism-based biomarkers. Ethical review committees at all collaborating institutions have approved this study. All results will be made available to the scientific community.

Preclinical studies have largely supported that alcohol-consumption induces the development of an important neuro-inflammation and this neuro-inflammation contributes to alcohol-drinking behaviors, notably through TLR4 and LPS related mechanisms. The neuro-inflammation originates from a direct interaction of ethanol with the neuronal and immune brain cells, but also from the generation of an inflammation at the periphery. Ethanol in particular interacts with the intestine to develop a gut dysbiosis and an increase in gut permeability, that allows the liberation of bacterial fragments to the systemic circulation and induces a pro-inflammatory response in the systemic circulation and peripheral organs, and in particular the liver. Peripheral cytokines or activated peripheral cells may cross the blood-brain barrier and activate neuro-inflammation. In humans, peripheral inflammation and intestinal dysbiosis are related to symptoms of alcohol use disorders (AUD), such as depression, anxi...

Loss of gut integrity is linked to various human diseases including inflammatory bowel disease. However, the mechanisms that lead to loss of barrier function remain poorly understood. Using D. melanogaster, we demonstrate that dietary restriction (DR) slows the agerelated decline in intestinal integrity by enhancing enterocyte cellular fitness through up-regulation of dMyc in the intestinal epithelium. Reduction of dMyc in enterocytes induced cell death, which leads to increased gut permeability and reduced lifespan upon DR. Genetic mosaic and epistasis analyses suggest that cell competition, whereby neighboring cells eliminate unfit cells by apoptosis, mediates cell death in enterocytes with reduced levels of dMyc. We observed that enterocyte apoptosis was necessary for the increased gut permeability and shortened lifespan upon loss of dMyc. Furthermore, moderate activation of dMyc in the post-mitotic enteroblasts and enterocytes was sufficient to extend health-span on rich nutrient diets. We propose that dMyc acts as a barometer of enterocyte cell fitness impacting intestinal barrier function in response to changes in diet and age.

Loss of gut integrity is linked to various human diseases including inflammatory bowel disease. However, the mechanisms that lead to loss of barrier function remain poorly understood. Using D. melanogaster, we demonstrate that dietary restriction (DR) slows the agerelated decline in intestinal integrity by enhancing enterocyte cellular fitness through up-regulation of dMyc in the intestinal epithelium. Reduction of dMyc in enterocytes induced cell death, which leads to increased gut permeability and reduced lifespan upon DR. Genetic mosaic and epistasis analyses suggest that cell competition, whereby neighboring cells eliminate unfit cells by apoptosis, mediates cell death in enterocytes with reduced levels of dMyc. We observed that enterocyte apoptosis was necessary for the increased gut permeability and shortened lifespan upon loss of dMyc. Furthermore, moderate activation of dMyc in the post-mitotic enteroblasts and enterocytes was sufficient to extend health-span on rich nutrient diets. We propose that dMyc acts as a barometer of enterocyte cell fitness impacting intestinal barrier function in response to changes in diet and age.

Diet is a major factor determining gut microbiota composition and perturbances in this complex ecosystem are associated with the inflammatory bowel disease (IBD). Here, we used gnotobiotic approach to analyze, how interaction between diet rich in proteins and gut microbiota influences the sensitivity to intestinal inflammation in murine model of ulcerative colitis. We found that diet rich in animal protein (aHPD) exacerbates acute dextran sulfate sodium (DSS)-induced colitis while diet rich in plant protein (pHPD) does not. The deleterious effect of aHPD was also apparent in chronic DSS colitis and was associated with distinct changes in gut bacteria and fungi. Therefore, we induced acute DSS-colitis in germ-free mice and transferred gut microbiota from aCD or aHPD fed mice to find that this effect requires presence of microbes and aHPD at the same time. The aHPD did not change the number of regulatory T cells or Th17 cells and still worsened the colitis in immuno-deficient RAG2 knockout mice suggesting that this effect was not dependent on adaptive immunity. The pro-inflammatory effect of aHPD was, however, abrogated when splenic macrophages were depleted with clodronate liposomes. This treatment prevented aHPD induced increase in colonic Ly-6C high pro-inflammatory monocytes, but the ratio of resident Ly-6C −/low macrophages was not changed. These data show that the interactions between dietary protein of animal origin and gut microbiota increase sensitivity to intestinal inflammation by promoting pro-inflammatory response of monocytes.

Background: Environmental Enteropathy (EE), characterized by alterations in intestinal structure, function, and immune activation, is believed to be an important contributor to childhood undernutrition and its associated morbidities, including stunting. Half of all global deaths in children < 5 years are attributable to under-nutrition, making the study of EE an area of critical priority. Methods: Community based intervention study, divided into two sub-studies, 1) Longitudinal analyses and 2) Biopsy studies for identification of EE features via omics analyses. Birth cohorts in Matiari, Pakistan established: moderately or severely malnourished (weight for height Z score (WHZ) < − 2) children, and well-nourished (WHZ > 0) children. Blood, urine, and fecal samples, for evaluation of potential biomarkers, will be collected at various time points from all participants (longitudinal analyses). Participants will receive appropriate educational and nutritional interventions; non-responders will undergo further evaluation to determine eligibility for further workup, including upper gastrointestinal endoscopy. Histopathological changes in duodenal biopsies will be compared with duodenal biopsies obtained from USA controls who have celiac disease, Crohn's disease, or who were found to have normal histopathology. RNA-Seq will be employed to characterize mucosal gene expression across groups. Duodenal biopsies, luminal aspirates from the duodenum, and fecal samples will be analyzed to define microbial community composition (omic analyses). The relationship between histopathology, mucosal gene expression, and community configuration will be assessed using a variety of bioinformatic tools to gain better understanding of disease pathogenesis and to identify mechanism-based biomarkers. Ethical review committees at all collaborating institutions have approved this study. All results will be made available to the scientific community.

Background: Environmental Enteropathy (EE), characterized by alterations in intestinal structure, function, and immune activation, is believed to be an important contributor to childhood undernutrition and its associated morbidities, including stunting. Half of all global deaths in children < 5 years are attributable to under-nutrition, making the study of EE an area of critical priority. Methods: Community based intervention study, divided into two sub-studies, 1) Longitudinal analyses and 2) Biopsy studies for identification of EE features via omics analyses. Birth cohorts in Matiari, Pakistan established: moderately or severely malnourished (weight for height Z score (WHZ) < − 2) children, and well-nourished (WHZ > 0) children. Blood, urine, and fecal samples, for evaluation of potential biomarkers, will be collected at various time points from all participants (longitudinal analyses). Participants will receive appropriate educational and nutritional interventions; non-responders will undergo further evaluation to determine eligibility for further workup, including upper gastrointestinal endoscopy. Histopathological changes in duodenal biopsies will be compared with duodenal biopsies obtained from USA controls who have celiac disease, Crohn's disease, or who were found to have normal histopathology. RNA-Seq will be employed to characterize mucosal gene expression across groups. Duodenal biopsies, luminal aspirates from the duodenum, and fecal samples will be analyzed to define microbial community composition (omic analyses). The relationship between histopathology, mucosal gene expression, and community configuration will be assessed using a variety of bioinformatic tools to gain better understanding of disease pathogenesis and to identify mechanism-based biomarkers. Ethical review committees at all collaborating institutions have approved this study. All results will be made available to the scientific community.

The potential impacts of methanol extract from Polygonatum odoratum on (YZM) colonic histopathology, gut gas production, short-chain fatty acids (SCFAs), and intestinal microbiota composition were evaluated with dextran sulfate sodium (DSS)-induced colitis mice in this study. These results indicated that YZM increased colon length and ameliorated colonic histopathology in DSS-induced colitis mice. Moreover, YZM administration reversed intestinal microbiota compositions leading to the inhibition of H2S-related bacteria (e.g., Desulfovibrionaceae) and the lower level of H2S and higher contents of SCFA-related bacteria (e.g., Muribaculaceae). Taken together, the effects of methanol extract from Polygonatum odoratum are studied to provide new enlightenment and clues for its application as a functional food and clinical drug. Our study first revealed the relationship between intestinal gas production and key bacteria in ulcerative colitis.

Intestinal disorders often occur in cancer patients, in association with body weight loss, and this alteration is commonly attributed to the chemotherapy. Here, using a mouse model of cancer cachexia induced by ectopic transplantation of C26 cancer cells, we discovered a profound alteration in the gut functions (gut permeability, epithelial turnover, gut immunity, microbial dysbiosis) independently of any chemotherapy. These alterations occurred independently of anorexia and were driven by interleukin 6. Gut dysfunction was found to be resistant to treatments with an anti-inflammatory bacterium (Faecalibacterium prausnitzii) or with gut peptides involved in intestinal cell renewal (teduglutide, a glucagon-like peptide 2 analogue). The translational value of our findings was evaluated in 152 colorectal and lung cancer patients with or without cachexia. The serum level of the lipopolysaccharidebinding protein, often presented as a reflection of the bacterial antigen load, was not only increased in cachectic mice and cancer patients, but also strongly correlated with the serum IL-6 level and predictive of death and cachexia occurrence in these patients. Altogether, our data highlight profound alterations of the intestinal homeostasis in cancer cachexia occurring independently of any chemotherapy and food intake reduction, with potential relevance in humans. In addition, we point out the lipopolysaccharide-binding protein as a new biomarker of cancer cachexia related to gut dysbiosis.

The role of gut barrier against pathogens and its interaction with dietary factors in weaned rabbits affected with digestive disorders, especially epizootic rabbit enteropathy is reviewed. This interaction was studied identifying nutritive factors that influence gut barrier function of mucosa. It was examined the morphology, and enzyme activity of mucosa and the gut associated immune system. Besides, it was characterized the substrate that reaches the caecum and its capacity to favour pathogen bacteria growth, by reviewing the effect of diet on ileal digestibility of nutrients, transit time and microbiota population. The nutritional factors which affect health of early weaned rabbits are level and type of both fibre and protein. The optimal dietary level of insoluble fibre to minimise mortality is 30-32%. Furthermore, a moderate inclusion of soluble fibre (12%) improves mucosa integrity and decreases mortality and the frequency of detection of Clostridium perfringens and Campylobacter spp in the caecum. The reduction of ileal nitrogen flow had a positive effect on pups viability and frequency of detection of C. perfringens. Furthermore, dietary supplementation with 1% of glutamine reduced fattening mortality, the frequency of detection of C. perfringens, and Helicobacter spp, and diminished the counts of Eimeria spp at the jejunum. In conclusion, a correct diet formulation may help to limit the epizootic rabbit enteropathy incidence in weaned rabbits.

Background: Electrical stimulation (ES) of several gastrointestinal (GI) segments is a promising therapeutic option for multilocular GI dysmotility, but conventional surgical access by laparotomy involves a high degree of tissue trauma. We evaluated a minimally invasive surgical approach using a robotic surgical system to perform electromyographic (EMG) recordings and ES of several porcine GI segments, comparing these data to an open surgical approach by laparotomy. Materials and Methods: In 5 acute porcine experiments, we placed multiple electrodes on the stomach, duodenum, jejunum, ileum, and colon. Three experiments were performed with a median laparotomy and 2 others using a robotic platform. Multichannel EMGs were recorded, and ES was sequentially delivered with 4 ES parameters to the 5 target segments. We calculated pre-and poststimulatory spikes per minute (Spm) and performed a statistical Poisson analysis. Results: Electrode placement was achieved in all cases without complications. Increased technical and implantation time were required to achieve the robotic electrode placement, but invasiveness was markedly reduced in comparison to the conventional approach. The highest calculated (c)Spm values were found in the poststimulatory period of the small bowel with both the conventional and robotic approaches. Six of the 20 Poisson test results in the open setup reached statistical significance and 12 were significant in the robotic experiments. Conclusions: The robotic setup was less invasive, revealed more consistent effects of multilocular ES in several GI segments, and is a promising option for future preclinical and clinical studies of GI motility disorders.

Pinocembrin (PIN) is a natural flavonoid widely found in bee propolis with potent gastrointestinal protective effects. In consequence, PIN has great potential in preventing inflammatory bowel diseases (IBDs) while scant information is available. In this study, a dextran sulfate sodium (DSS)-induced rats ulcerative colitis model (3.5% DSS in drinking water for 7 days) was applied to explore the protective effects of PIN on macroscopic colitis symptoms, inflammation, intestinal epithelial barrier function, and gut microbiota homeostasis. While DSS-treated rats showed severe colitis clinical symptoms and histological changes (colonic pathological damages and intestinal goblet cells loss), pre-administration of PIN (5 and 10 mg/kg, p.o.) for a week alleviated these symptoms. Pre-administration of PIN also suppressed the pro-inflammatory gene expressions and improved tight junction functions of colonic epithelial cells. Additionally, PIN administration reversed DSS-induced short chain fatty acid loss, and improved the gut microbial diversity assessed by 16S rRNA phylogenetic sequencing. Overall, our results suggest a wide spectrum of protective effects of PIN in preventing IBDs.

Pinocembrin (PIN) is a natural flavonoid widely found in bee propolis with potent gastrointestinal protective effects. In consequence, PIN has great potential in preventing inflammatory bowel diseases (IBDs) while scant information is available. In this study, a dextran sulfate sodium (DSS)-induced rats ulcerative colitis model (3.5% DSS in drinking water for 7 days) was applied to explore the protective effects of PIN on macroscopic colitis symptoms, inflammation, intestinal epithelial barrier function, and gut microbiota homeostasis. While DSS-treated rats showed severe colitis clinical symptoms and histological changes (colonic pathological damages and intestinal goblet cells loss), pre-administration of PIN (5 and 10 mg/kg, p.o.) for a week alleviated these symptoms. Pre-administration of PIN also suppressed the pro-inflammatory gene expressions and improved tight junction functions of colonic epithelial cells. Additionally, PIN administration reversed DSS-induced short chain fatty acid loss, and improved the gut microbial diversity assessed by 16S rRNA phylogenetic sequencing. Overall, our results suggest a wide spectrum of protective effects of PIN in preventing IBDs.

Interdigestive intestinal motility, and especially phase III of the migrating myoelectric/motor complex (MMC), is responsible for intestinal clearance and plays an important role in prevention of bacterial overgrowth and translocation in the gut. Yet previous results from gnotobiotic rats have shown that intestinal microflora can themselves affect the characteristics of the myoelectric activity of the gut during the interdigestive state. Given that the composition of the intestinal microflora can be altered by dietary manipulations, we investigated the effect of supplementation of the diet with synbiotics on intestinal microflora structure and the duodenojejunal myoelectric activity in the rat. To reduce animal distress caused by restraint and handling, which can itself affect GI motility, we applied radiotelemetry for duodenojejunal EMG recordings in conscious, freely moving rats. Thirty 16-month-old Spraque-Dawley rats were used. The diet for 15 rats (E group) was supplemented with chicory inulin, Lactobacillus rhamnosus and Bifidobacterium lactis. The remaining 15 rats were fed control diet without supplements (C group). Three rats from each group were implanted with three bipolar electrodes positioned at 2, 14 and 28 cm distal to the pylorus. After recovery, two 6 h recordings of duodenojejunal EMG were carried out on each operated rat. Subsequently, group C rats received feed supplements and group E rats received only control diet for 1 week, and an additional two 6 h recordings were carried out on each of these rats. Non-operated C and E rats were killed and samples of GI tract were collected for microbiological analyses. Supplementation of the diet with the pro-and prebiotics mixture increased the number of bifidobacteria, whereas it decreased the number of enterobacteria in jejunum, ileum, caecum and colon. In both caecum and colon, the dietary supplementation increased the number of total anaerobes and lactobacilli. Treatment with synbiotics increased occurrence of phase III of the MMC at all three levels of the small intestine. The propagation velocity of phase III in the whole recording segment was also increased from 3.7 ± 0.2 to 4.4 ± 0.2 cm min −1 by dietary treatment. Treatment with synbiotics increased the frequency of response potentials of the propagated phase III of the MMC at both levels of the jejunum, but not in the duodenum. In both parts of the jejunum, the supplementation of the diet significantly decreased the duration of phase II of the MMC, while it did not change the duration of phase I and phase III. Using the telemetry technique it was demonstrated that changes in the gastrointestinal microflora exhibited an intestinal motility response and, more importantly, that such changes can be initiated by the addition of synbiotics to the diet.

Purpose: Simplified liquid nutrition is an effective means of nutrient delivery for individuals suffering from certain chronic diseases, such as short bowel disease, Crohn's disease, and certain cancers of the head and neck. However, a simplified liquid diet can lead to gut barrier and gut-associated lymphoid tissue (GALT) dysfunction partially due to the lack of protein, oligosaccharides, and other dietary macro constituent complexity when compared with normal, solid food nutrition. Gut barrier function and GALT are key components in maintaining both physical and immunological protection against pathogenic bacteria and antigens. Previous research has demonstrated that the addition of cranberry proanthocyanidins (c-PAC), a class of non-nutritive plant defensive compounds, to elemental enteral nutrition (EEN) results in an increase compared to controls of goblet cell concentration, MUC2 production, Peyer's patch lymphocytes, intestinal villi length, and crypt depth in a mouse model of gut barrier dysfunction. Additionally, sIgA and IL-4 levels showed an increase with the c-PAC enriched EEN formula, suggesting an increase in GALT function. To gain a deeper understanding of the mechanisms by which c-PAC improves physical and immunologic aspects of gut barrier function, we have developed an in vitro extraintestinal pathogenic E. coli (ExPEC) challenge to a co-culture (Caco-2 and macrophage) model system resulting in a simplified model of gut barrier dysfunction. Using this in vitro challenge model we : 1) Examined the physical mechanism of gut barrier function by monitoring trans epithelial electrical resistance (TEER), and 2) Evaluated macrophage expression of inflammatory proteins (iNOS, TNF-, and COX-2). Methods: We developed an in vitro co-culture model of gut barrier dysfunction that employed a gut epithelial cell monolayer on transwells that were co-cultured with macrophages adhered to the culture plate on the basolateral side of the monolayer. The cells were challenged with ExPEC on the apical side of the monolayer both with and without c-PAC present. TEER values of the epithelial cell membrane were measured to evaluate gut barrier function. Additionally, the macrophages on the basolateral side of the cell co-culture model were lysed and the expression of pro-inflammatory proteins was qualitatively assessed using Western Blot technology. Results: TEER declined by ~80% and markers of macrophage activation increased compared to controls when Caco-2 cells were challenged with ExPEC for 24 hours. When Caco-2 cells previously treated with a c-PAC enriched media were challenged with ExPEC, the decrease in TEER was attenuated (Figure 1) and macrophage expression of inflammatory proteins, cyclooxygenase-2 (COX-2), was reduced (Figure 2). Conclusion: These results demonstrate the ability of this in vitro cell co-culture model to perform both a quantitative and qualitative analysis of the mechanisms of gut barrier function. We are continuing to research these effects to further determine the efficacy of c-PAC to attenuate both ExPEC and EN induced barrier dysfunction and subsequent macrophage activation. This technology will be an important tool for optimizing EN formulas.