Search Results (40)

The gastrointestinal (GI) barrier is a highly coordinated, multilayered defence system that maintains intestinal homeostasis by separating the luminal microbiota from the internal milieu. In liver cirrhosis, this barrier undergoes profound structural and functional disruption, emerging as a central driver of bacterial translocation and infection-related complications. Among these, spontaneous bacterial peritonitis (SBP) represents a major determinant of morbidity, mortality, and disease progression. Barrier failure in cirrhosis is not attributable to a single defect but results from the convergence of multiple interconnected mechanisms. Structural alterations include disruption of epithelial tight junctions and deterioration of the mucus layer, leading to increased intestinal permeability and loss of spatial compartmentalisation. These changes are compounded by microbial dysbiosis, characterised by reduced diversity, depletion of short-chain fatty acid-producing taxa, and expansion of pathobionts. In parallel, cirrhosis-associated immune dysfunction impairs both mucosal and systemic antimicrobial defences, while gut–vascular barrier disruption facilitates systemic dissemination of bacteria and microbial products. The resulting increase in bacterial translocation plays a pivotal role in the pathogenesis of SBP and contributes to systemic inflammation, circulatory dysfunction, and acute decompensation. Importantly, this process establishes a self-amplifying pathogenic loop in which barrier dysfunction, dysbiosis, and immune dysregulation mutually reinforce each other. Recent advances have identified key molecular pathways involved in barrier regulation, including bile acid–FXR signalling and microbiome-derived metabolites, providing novel targets for therapeutic intervention. While current management relies largely on antibiotics and supportive care, emerging strategies aim to restore barrier integrity and modulate the gut–liver axis. A deeper understanding of GI barrier dysfunction offers new opportunities to prevent bacterial translocation and improve clinical outcomes in patients with liver cirrhosis. Full article

Crohn’s disease (CD) is characterized by chronic intestinal inflammation accompanied by gut dysbiosis and redox imbalance. We investigated the role of dual oxidase-2 (DUOX2), a major epithelial source of reactive oxygen species (ROS), in linking oxidative stress to microbe–host crosstalk. DUOX2 expression was upregulated in human intestinal samples and was positively associated with inflammatory readouts, oxidative stress indices, and dysbiosis. Intestinal epithelial cell-specific Duox2 knockout (KO) mice exhibited reduced mucosal ROS, preserved barrier integrity, and attenuated dextran sodium sulfate (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Cohousing and fecal microbiota transplantation demonstrated that this protective phenotype was microbiota-dependent. Multi-omics profiling identified enrichment of Parabacteroides, particularly P. distasonis, in Duox2 KO mice, and oral supplementation with P. distasonis enhanced resistance to colitis. Mechanistically, DUOX2-derived oxidative stress constrained Parabacteroides growth, as P. distasonis displayed marked susceptibility to hydrogen peroxide, with excessive intracellular ROS accumulation and an absence of key antioxidant defenses—including peroxide reductase C (AhpC) and superoxide dismutase B (SodB)—indicating that epithelial DUOX2 shapes a hostile luminal redox niche unfavorable to these beneficial microbes. Pharmacological inhibition of DUOX2 with Compound 521 reduced oxidative stress, ameliorated colitis, and partially restored microbial balance. These findings establish a DUOX2–ROS–microbiota axis in which epithelial DUOX2 amplifies oxidative stress, remodels the gut ecosystem, and promotes inflammation, and highlights DUOX2 suppression or ROS-sensitive Parabacteroides as potential redox-centric therapeutic strategies for CD. Full article

This study systematically characterized functional compartmentalization along the intestinal tract of New Zealand rabbits by analyzing mucosal tissue and luminal contents from distinct segments, including the duodenum, jejunum, ileum, cecum, and colon, using RNA-seq and 16S rRNA sequencing. Transcriptomic analysis revealed that differentially expressed genes identified between the small and large intestines were mainly enriched in digestion, absorption, and immune functions. Genes associated with the transport of amino acids, sugars, vitamins, and bile salts showed significantly higher expression in the small intestine, whereas genes related to water absorption, short-chain fatty acids (SCFAs), nucleotides, and metal ion transport were preferentially expressed in the large intestine. From an immunological perspective, genes involved in fungal responses were enriched in the small intestine, while bacterial response pathways and pattern recognition receptor (PRR) signaling genes were upregulated in the large intestine. Microbiota analysis demonstrated significantly greater diversity and abundance in the large intestine compared with the small intestine. Specifically, Proteobacteria and Actinobacteria were enriched in the small intestine, whereas Firmicutes, Verrucomicrobia, and Bacteroidetes dominated the large intestine. Correlation analysis further identified significant associations between gut microbiota composition and host genes involved in nutrient digestion and absorption. Together, these findings provide transcriptome-based evidence for regional specialization of nutrient transport, immune responses, and microbial ecology along the rabbit intestine. Full article

Recently, the role of mucosal intestinal microbiota in human health has received increasing attention. Nevertheless, data on the response of this microbiota to various interventions remain limited. Here, we have employed the Mucosal Simulator of Human Gastrointestinal Microbial Ecosystem (M-SHIME^®) and luminal SHIME^® (L-SHIME^®) to examine mucosal microbiota responses to interventions that are known to impact the intestinal microbial community in humans and study relationships between the responses of mucosal and luminal microbiota. Specifically, we evaluated the effects of varying macronutrient levels over a 28-day standard, balanced dietary intervention and a parallel 14-day administration of Lacticaseibacillus rhamnosus GG. Observed shifts in mucosal microbiota in response to interventions differed significantly from those observed in luminal microbiota (p < 0.05). In particular, we found that the mucosal microbiota compared to luminal microbiota was more stable and that the abundance of several genera (i.e., Subdoligranulum, Parabacteroides and Fusobacterium) in the M-SHIME^® correlated positively with the intake of dietary macronutrients, especially protein, which was in line with results reported in previous human studies. This study demonstrates the reliability of advanced in vitro models in capturing diet-induced dynamics of the human mucosal microbiota, a compartment that remains understudied despite its critical role in intestinal immune regulation. Full article

Background/Objectives: This study examines the application of the novel double emulsion gel system for the delivery and release of encapsulated cannabidiol (CBD) and the probiotic strain Lactiplantibacillus plantarum DSM 24624. Methods: During a six-week experimental period comprising stabilization, treatment, and wash-out phases, the dynamic Simulator of the Human Intestinal Microbial Ecosystem (SHIME^®) model was employed to assess a system. The evaluation focused on the delivery of CBD and probiotics, as well as the system’s effects on microbial composition, diversity, and metabolic activity throughout the digestion process using 16S rRNA gene sequencing and digital PCR methods. Results: Microbial community analysis revealed significant shifts in both mucosal and luminal microbiota following supplementation. The treatment increased beneficial bacterial families such as Lachnospiraceae and Clostridiaceae, demonstrated effective delivery, release, and persistence of the probiotic L. plantarum, as well as enhanced butyrate and lactate production. Diversity analyses highlighted a transient rise in alpha diversity within the mucin layer and a decrease in the lumen, with significant changes in beta diversity across experimental phases. Conclusions: Findings suggest that double emulsion gel can be employed for the delivery of probiotics and CBD to the gastrointestinal tract. In addition, an innovative CBD-probiotic formulation can modulate gut microbiota composition and metabolic activity, suggesting its potential as a functional food innovation for intestinal health. However, the results are based on an in vitro model, which lacks the complexity of the human host environment, and further clinical studies are necessary to confirm the biological relevance and therapeutic potential of such delivery systems for gastrointestinal health. Full article

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease, are chronic disorders relating to gut microbiota dysbiosis. Despite severe pancolitis being more prevalent in pediatric UC than in adults, alterations in the colon mucosa-associated microbiota (MAM) and their association with disease severity remain to be elucidated. The present study aimed to compare the gut microbiota in colon lavage fluids (CLFs) and fecal samples from 19 pediatric UC and 19 non-IBD patients. The community structure of MAM inferred by 16S metagenomic analysis was similar throughout the colon regardless of disease type. Bacterial compositions between MAM and feces were significantly different in non-IBD, while no difference was observed in pediatric UC, indicating a compromised mucous layer that could not sufficiently separate the MAM and luminal microbiota in UC. In pediatric UC, homogenous distribution of MAM was gradually disordered with increases in disease activity or mucosal inflammation, and bacterial groups of upper digestive tract or environmental origin were more abundant in MAM. Monitoring key bacterial markers in MAM, which include Lactobacillus and Enterococcus or Faecalibacterium and Blautia as increased or reduced members in pediatric UC, respectively, might be useful for evaluation of patient prognosis. Full article

Ulcerative colitis (UC) is caused by an excessive immune response to gut microbiota. A recent study reported that the population of IgG-coated gut microbes increases with disease severity in patients with UC, but the role of these IgG-coated microbes in UC pathology is unclear. Serum, feces and colonoscopic lavage fluids (CLFs) were collected from pediatric UC (n = 13) and non-inflammatory bowel disease (IBD) patients (n = 15). Gut microbes were isolated from feces. Serum IgG reactivity to microbial cells and CLF-derived proteins was evaluated by Western blotting. Complement activation by the bacteria–IgG complexes was also assessed. Serum IgG reactivity to gut microbial extracts was highly variable in patients with active UC and increased with mucosal inflammation. IgG reactivity and clinical condition were inversely associated depending on disease activity. Non-IBD patients showed a similar degree of serum IgG response as that seen for patients whose UC was in remission. Lactobacillaceae bound higher amounts of IgG than other gut microbes tested and absorbed IgG to other bacteria. Lacticaseibacillus paracasei suppressed complement activation by Escherichia coli—IgG immune complexes. Appropriate IgG responses to luminal microbes might play a key role in gut microbiota stability by reducing excessive mucosal inflammation. Full article

The aim of this study was to investigate the microbiota composition and its potential interactions across seven gut locations (stomachs, jejuna, ilea, ceca, proximal colons, distal colons, and recta) in weaned pigs to identify key influencing microbiotas. To compare between microbiota compositions, 16S rRNA gene amplicon sequencing was performed. Six 70-day-old healthy crossbred (Duroc × Large White × Landrace) piglets were introduced as donors. A Bayesian network (BN) was used to examine the directional interactions among the microbiotas evaluated (seven mucosal and seven digesta microbiotas). Based on edge connectivity frequency, the microbiota in jejunal mucosa was the central hub node, influencing other microbiotas, especially the mucosal microbiotas of the ileum, cecum, distal colon, and rectum. The jejunal mucosa was dominated by Prevotella and lactobacilli, both recognized for their contributions to pig health. Among Prevotella, Prevotella copri and Prevotella sp. were predominant in jejunal mucosa (4.6% and 2.9%, respectively). Lactobacilli, including eight distinct species, were distributed throughout the gastrointestinal tract. Notably, Ligilactobacillus salivarius and Lactobacillus amylovorus, known as immune-enhancing bacteria, were abundant in jejunal mucosa (1.0% and 0.8%) and digestas (0.9% and 19.2%), respectively. The BN identified rectal mucosa and digestas as two terminal nodes, influenced by upstream microbiotas in the gastrointestinal tract. This finding supports the link between fecal microbiota and pig productivity, as the fecal microbiota, closely resembling the rectal microbiota, reflects the conditions of the microbiota throughout the gastrointestinal tract. Full article

The gut microbiota plays a crucial role in dogs’ health, influencing immune function, digestion, and protection against pathogens. This study evaluates the effects of three canine dietary supplements—Microbiotal (prebiotic), Lactobacillus reuteri (probiotic), and a combination of both—on the gut microbiota composition of a healthy canine donor using an in vitro colonic fermentation model. The SCIME™ platform, adapted to simulate the canine gastrointestinal tract, was used to monitor microbial shifts in the luminal and mucosal environments of the proximal and distal colon over a 2-week treatment period. The microbial communities were analyzed using 16S rRNA sequencing to assess changes at various taxonomic levels. Alpha- and beta-diversity indices were calculated, while LEfSe and treeclimbR were employed to identify taxa-driving microbial shifts. Results indicated that all treatments led to significant modulations in key microbial groups, with enrichment of Limosilactobacillus, Bifidobacterium, Prevotella, and Faecalibacterium. These changes suggest improved saccharolytic fermentation and butyrate production, particularly when prebiotics and probiotics were co-administered. This study highlights the promising benefits of combined prebiotic and probiotic supplementation in promoting gut health and microbial diversity, providing a basis for future studies targeting the metabolic activity of the gut microbiota using the same supplements and technology. Full article

The present study was undertaken to evaluate the impacts of nano-composites of copper and carbon (NCCC) on the intestinal luminal micro-ecosystem and mucosal homeostasis of yellow-feather broilers. A total of two-hundred and forty 1-day-old male yellow-feather broilers were randomly allocated into four groups, each with five replications of twelve birds. The control (CON) group received a corn-soybean basal diet, while the N50, N100, and N200 groups were supplemented with 50, 100, and 200 mg/kg of NCCC in basal diets, respectively. The trial duration was 63 days. The findings demonstrated that there were slight impacts of NCCC addition on the intestinal luminal micro-ecosystem of broilers, with the fecal moisture content in the N100 group being slightly higher on Day 3 in the starter phase (p < 0.05). The cecal microbiota structure also did not obviously change (p > 0.05), in spite of the fall in the relative abundance of the Ruminococcus torques group in the N50 group and norank Clostridia UCG-014 in N200 group (p < 0.05). But for intestinal mucosal homeostasis, NCCC played a crucial part in jejunal morphology, tight junction, immunologic status, and antioxidant capacity. There was linear growth in villus height and a quadratic increase in villus height, crypt depth and their ratio with the increase in NCCC dosage (p < 0.05), and 100 mg/kg NCCC supplementation could intensify the expression of CLDN-3 genes (p < 0.05). In addition, IL-4 and IL-10 linearly increased after NCCC treatment (p < 0.05), along with some irregular changes in sIgA (p < 0.05). In addition, higher jejunal mucosal total antioxidant capacities in N50 and N200 groups were also observed (p < 0.05). Overall, NCCC treatment optimized the intestinal mucosa function of broilers in terms of physical barrier and immune and antioxidant capacities, but exerted subtle influence in the luminal environment of yellow-feather broilers. More precisely, dietary supplementation with 50 mg/kg NCCC is recommended for intestinal homeostasis of broilers. Full article

Coccidiosis in broiler chickens continues to be a major disease of the gastrointestinal tract, causing economic losses to the poultry industry worldwide. The goal of this study was to generate a symptomatic Eimeria maxima (1000 oocysts) infection to determine its effect on the luminal and mucosal microbiota populations (L and M) in the jejunum and ileum (J and IL). Samples were taken from day 0 to 14 post-infection, and sequencing of 16S rRNA was performed using Illumina technology. Infected birds had significantly (p < 0.0001) lower body weight gain (BWG), higher feed conversion ratio (FCR) (p = 0.0015), increased crypt depth, and decreased villus height (p < 0.05). The significant differences in alpha and beta diversity were observed primarily at height of infection (D7). Analysis of taxonomy indicated that J-L and M were dominated by Lactobacillus, and in IL-M, changeover from Candidatus Arthromitus to Lactobacillus as the major taxon was observed, which occurred quicky in infected animals. LEfSe analysis found that in the J-M of infected chickens, Lactobacillus was significantly more abundant in infected (IF) chickens. These findings show that E. maxima infection affects the microbiota of the small intestine in a time-dependent manner, with different effects on the luminal and mucosal populations. Full article

The objectives of this review are to investigate how benzoic acid can mitigate the negative effects of weaning stress, improve the intestinal microbiota, intestinal health, and growth of nursery pigs, determine the optimal dose level of benzoic acid for the growth rate in nursery pigs, and compare the efficacy of benzoic acid and other acids in pig feeds. After weaning, pigs are exposed to less lactose and solid feed with high acid-binding capacity at infrequent intervals, causing an increase in digesta pH, reducing protein digestion, and increasing ammonia-producing bacteria in the stomach. Benzoic acid supplementation has improved the intestinal health and growth of nursery pigs through its antimicrobial properties and pH reduction in the digesta. The positive modulation of luminal microbiota in the small intestine of pigs by benzoic acid improves intestinal morphology and enhances nutrient utilization, especially nitrogen, of nursery pigs. Benzoic acid supplementation of up to 1% in feeds also increases hippuric acid contents in the urine of nursery pigs, decreasing urinary pH, which is related to ammonia emission and barn conditions in intensive pig production. Supported by the beneficial impacts of benzoic acid, the growth performance of nursery pigs was also improved. However, excessive benzoic acid (over 2.5% up to 5%) in feeds reduces the growth performance of nursery pigs. Thus, this review conducted a meta-analysis of the results from 16 papers to determine the optimal dose level of benzoic acid for body weight gain of nursery pigs, which was found to be 0.60%. The efficacy of benzoic acid was similar to that of other organic acids, including citric acid, fumaric acid, formic acid, and formate salts. Collectively, benzoic acid supplementation can positively modulate the luminal and mucosal microbiota in the small intestine, increase nutrient utilization and intestinal health, decrease urinary pH, and improve the growth performance of nursery pigs. Full article

Enterohemorrhagic Escherichia coli (EHEC) is a major food-borne pathogen that causes human disease ranging from diarrhea to life-threatening complications. Accumulating evidence demonstrates that the Western diet enhances the susceptibility to enteric infection in mice, but the effect of diet on EHEC colonization and the role of human gut microbiota remains unknown. Our research aimed to investigate the effects of a Standard versus a Western diet on EHEC colonization in the human in vitro Mucosal ARtificial COLon (M-ARCOL) and the associated changes in the gut microbiota composition and activities. After donor selection using simplified fecal batch experiments, two M-ARCOL bioreactors were inoculated with a human fecal sample (n = 4) and were run in parallel, one receiving a Standard diet, the other a Western diet and infected with EHEC O157:H7 strain EDL933. EHEC colonization was dependent on the donor and diet in the luminal samples, but was maintained in the mucosal compartment without elimination, suggesting a favorable niche for the pathogen, and may act as a reservoir. The Western diet also impacted the bacterial short-chain fatty acid and bile acid profiles, with a possible link between high butyrate concentrations and prolonged EHEC colonization. The work demonstrates the application of a complex in vitro model to provide insights into diet, microbiota, and pathogen interactions in the human gut. Full article

In this study, the effects of a homogenous porphyran from Porphyra haitanensis (PHP) on the intestinal barrier and gut microbiota were investigated. The results showed that oral administration of PHP resulted in a higher luminal moisture content and a lower pH environment for the growth of beneficial bacteria in the colon of mice. PHP significantly increased the production of total short-chain fatty acids during the fermentation process. PHP made the intestinal epithelial cells of mice arrange more tidily and tightly with a significant increase in mucosal thickness. PHP also increased the amount of mucin-producing goblet cells and the expression of mucin in the colon, which maintained the structure and function of the intestinal mucosal barrier. Moreover, PHP up-regulated the expression of tight junctions including ZO-1 and occludin, improving the intestinal physical barrier function. The results of 16S rRNA sequencing showed that PHP regulated the composition of gut microbiota in mice, increasing the richness and diversity of gut microbiota and the ratio of Firmicutes to Bacteroidetes. This study revealed that the intake of PHP is beneficial for the gastrointestinal tract and PHP could be a potential source of prebiotics in the functional food and pharmaceutical industries. Full article

Alterations in gut microbiota play a pivotal role in the adenoma-carcinoma sequence. However, there is still a notable lack of the correct implementation of tissue and fecal sampling in the setting of human gut microbiota examination. This study aimed to review the literature and to consolidate the current evidence on the use of mucosa and a stool-based matrix investigating human gut microbiota changes in precancerous colorectal lesions. A systematic review of papers from 2012 until November 2022 published on the PubMed and Web of Science databases was conducted. The majority of the included studies have significantly associated gut microbial dysbiosis with premalignant polyps in the colorectum. Although methodological differences hampered the precise fecal and tissue-derived dysbiosis comparison, the analysis revealed several common characteristics in stool-based and fecal-derived gut microbiota structures in patients with colorectal polyps: simple or advanced adenomas, serrated lesions, and carcinomas in situ. The mucosal samples considered were more relevant for the evaluation of microbiota’s pathophysiological involvement in CR carcinogenesis, while non-invasive stool sampling could be beneficial for early CRC detection strategies in the future. Further studies are required to identify and validate mucosa-associated and luminal colorectal microbial patterns and their role in CRC carcinogenesis, as well as in the clinical setting of human microbiota studies. Full article