• Lactiplantibacillus plantarum
• anti-photoaging
• extracellular vesicles
• gut–skin axis
• intestinal inflammation

• IBD
• Intestinal microbiota
• Metabolites
• Microbial treatments
• Structure and function

• Dysbiosis/microbiology
• Dysbiosis/therapy
• Gastrointestinal Microbiome
• Humans
• Inflammatory Bowel Diseases/microbiology
• Inflammatory Bowel Diseases/therapy
• Microbiota

Probiotics are used in the food industry as feed additives to maintain the balance of animal gut microbiota. They are also considered to have potential therapeutic effects against liver diseases. This study showed that dietary Lactobacillus supplementation improved liver function and reduced cholesterol levels in Jeju native pigs, with Toll-like receptors (TLR) signaling as the primary response in the gut against Lactobacillus and TNF-α/IFN-γ as the central mediator cytokines in the gut and liver tissues. Lactobacillus supplementation may be applied to treat metabolic disorders of the liver, especially cholesterol-related disorders, in farm animals.

We evaluated the dietary effects of multiple probiotics in Jeju native pigs, using basal diet and multi-probiotic Lactobacillus (basal diet with 1% multi-probiotics) treatments (n = 9 each) for 3 months. We analyzed growth performance, feed efficiency, backfat thickness, blood parameters, hematological profiles, adipokines, and immune-related cytokines in pig tissues. Average daily gain, feed intake, feed efficiency, backfat thickness, and body weight were not significantly different between both groups. In Lactobacillus group, total protein (p < 0.08) and bilirubin (p < 0.03) concentrations increased; blood urea nitrogen (p < 0.08), alkaline phosphatase (p < 0.08), and gamma-glutamyltransferase (p < 0.08) activities decreased. Lactobacillus group showed decreased adiponectin (p < 0.05), chemerin (p < 0.05), and visfatin expression in adipose tissues, and increased TLR4 (p < 0.05), MYD88 (p < 0.05), TNF-α (p < 0.001), and IFN-γ (p < 0.001) expression in the liver. Additionally, NOD1 (p < 0.05), NOD2 (p < 0.01), and MYD88 (p < 0.05) mRNA levels in proximal colon tissue upregulated significantly. Colon, longissimus dorsi muscle, fat tissue, and liver histological analyses revealed no significant differences between the groups. Conclusively, Lactobacillus supplementation improved liver function and reduced cholesterol levels. Its application may treat metabolic liver disorders, especially cholesterol-related disorders.

• Lactobacillus
• adipokine
• cholesterol
• liver function
• probiotic

The gastrointestinal tract is a functionally and anatomically segmented organ that is colonized by microbial communities from birth. While the genetics of mouse gut development is increasingly understood, how nutritional factors and the commensal gut microbiota act in concert to shape tissue organization and morphology of this rapidly renewing organ remains enigmatic. Here, we provide an overview of embryonic mouse gut development, with a focus on the intestinal vasculature and the enteric nervous system. We review how nutrition and the gut microbiota affect the adaptation of cellular and morphologic properties of the intestine, and how these processes are interconnected with innate immunity. Furthermore, we discuss how nutritional and microbial factors impact the renewal and differentiation of the epithelial lineage, influence the adaptation of capillary networks organized in villus structures, and shape the enteric nervous system and the intestinal smooth muscle layers. Intriguingly, the anatomy of the gut shows remarkable flexibility to nutritional and microbial challenges in the adult organism.

• development
• endothelium
• enteric nervous system
• epithelial cells
• high-fat diet
• immunometabolism
• intestine
• microbiota
• morphology
• nutrition
• vascularization

• diabetes mellitus
• entero-insular axis
• mRNA
• pentoxifylline

• hydrogen sulfide
• inflammatory bowel diseases
• intestinal microbiome
• meta-analysis
• sulfate-reducing bacteria
• ulcerative colitis

• MUNI/A/0947/2019 Masarykova Univerzita

• CD
• Crohn’s disease
• UC
• inflammation
• inflammatory bowel disease
• prebiotics
• probiotics
• psoriasis
• rheumatoid arthritis
• ulcerative colitis

• Arthritis, Rheumatoid/diet therapy
• Arthritis, Rheumatoid/immunology
• Autoimmune Diseases/diet therapy
• Autoimmune Diseases/immunology
• Curcumin/administration & dosage
• Dietary Supplements
• Female
• Fish Oils/administration & dosage
• Humans
• Inflammatory Bowel Diseases/diet therapy
• Inflammatory Bowel Diseases/immunology
• Male
• Prebiotics/administration & dosage
• Probiotics/administration & dosage
• Psoriasis/diet therapy
• Psoriasis/immunology
• Vitamin D/administration & dosage

• K08 AR072144 NIAMS NIH HHS

There is growing interest in studying dietary fiber to stimulate microbiome changes that might prevent or alleviate inflammatory bowel disease (IBD). However, dietary fiber effects have shown varying degrees of efficacy, for reasons that are unclear. This study examined whether the effects of isomaltodextrin on gut microbiota and IBD were dependent on dose or host sex, using an Interleukin (IL)-10 deficient murine colitis model. After 12 weeks, colonic IL-12p70 was depressed in male mice receiving high-dose isomaltodextrin supplementation compared to the control group (p = 0.04). Male mice receiving high-dose isomaltodextrin exhibited changes in microbial alpha-diversity, including enhanced richness and evenness (p = 0.01) and limited reduction in the relative abundance of Coprococcus (q = 0.08), compared to the control group. These microbial compositional changes were negatively associated with IL-12p70 levels in the male group (rs ≤ −0.51, q ≤ 0.08). In contrast, female mice receiving isomaltodextrin displayed a reduction in alpha-diversity and Coprococcus abundance and a high level of IL-12p70, as did the control group. Together, these results indicate that isomaltodextrin altered the gut microbial composition linking specific immune-regulatory cytokine responses, while the interactions among fiber, microbiota and immune response were dose dependent and largely sex specific. The results further indicate that interactions between environmental and host factors can affect microbiome manipulation in the host.

• colitis
• cytokines
• dietary fiber
• gut microbiota
• isomaltodextrin
• sex differences

Dysfunction of intestinal epithelial Cl⁻ currents and channels have previously been reported in inflammatory intestinal diseases. However, the expression and function of the newly identified Ca²⁺-activated Cl⁻ channel transmembrane member 16A (TMEM16A) in the intestinal epithelium is unclear. In this study, we investigated the effects of TMEM16A on intestinal epithelial barrier function in vitro. Intestinal epithelial barrier dysfunction was modeled by lipopolysaccharide (LPS)-induced cell damage in intestinal epithelial IEC-6 cells and the effects of TMEM16A knockdown and overexpression on cell apoptosis and tight junctions were studied. Corresponding mRNA and protein expression levels were measured by quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence analysis, respectively. TMEM16A expression was significantly increased by LPS, possibly via a process involving the transcription factor nuclear factor-κB and both Th1 and Th2 cytokines. Low- and high-dose LPS dysregulated tight junctions (high-myosin light-chain kinase expression) and cell apoptosis-dependent cell barrier dysfunction, respectively. TMEM16A aggravated cell barrier dysfunction in IEC-6 cells pretreated with low-dose LPS by activating ERK1/MLCK signaling pathways, but protected against cell barrier dysfunction by activating ERK/Bcl-2/Bax signaling pathways in IEC-6 cells pretreated with high-dose LPS. We concluded that TMEM16A played a dual role in LPS-induced epithelial dysfunction in vitro. The present results indicated the complex regulatory mechanisms and targeting of TMEM16A may provide potential treatment strategies for intestinal epithelial barrier damage, as well as forming the basis for future studies of the expression and function of TMEM16A in normal and inflammatory intestinal diseases in vivo.

Infectious bronchitis virus (IBV), a member of the Coronaviridae family, causes serious losses to the poultry industry. Intestinal microbiota play an important role in chicken health and contribute to the defence against colonization by invading pathogens. The aim of this study was to investigate the link between the intestinal microbiome and nephropathogenic IBV (NIBV) infection. Initially, chickens were randomly distributed into 2 groups: the normal group (INC) and the infected group (IIBV). The ilea were collected for morphological assessment, and the ileal contents were collected for 16S rRNA gene sequencing analysis. The results of the IIBV group analyses showed a significant decrease in the ratio of villus height to crypt depth (P < 0.05), while the goblet cells increased compared to those in the INC group. Furthermore, the microbial diversity in the ilea decreased and overrepresentation of Enterobacteriaceae and underrepresentation of Chloroplast and Clostridia was found in the NIBV-infected chickens. In conclusion, these results showed that the significant separation of the two groups and the characterization of the gut microbiome profiles of the chickens with NIBV infection may provide valuable information and promising biomarkers for the diagnosis of this disease.

• Colitis, Ulcerative/microbiology
• Crohn Disease/microbiology
• Gastrointestinal Microbiome/physiology
• Humans

• C/EBPδ
• apoptosis
• colitis
• dextran sodium sulfate
• inflammatory bowel disease

Gastrointestinal microbiome has drawn an increasing amount of attention over the past decades. There is emerging evidence that the gut flora plays a major role in the pathogenesis of certain diseases. We aimed to analyze the evolution of gastrointestinal microbiome research and evaluate publications qualitatively and quantitatively.

We obtained a record of 2891 manuscripts published between 1998 and 2018 from the Web of Science Core Collection (WoSCC) of Thomson Reuters; this record was obtained on June 23, 2018. The WoSCC is the most frequently used source of scientific information. We used the term “Gastrointestinal Microbiomes” and all of its hyponyms to retrieve the record, and restricted the subjects to gastroenterology and hepatology. We then derived a clustered network from 70,169 references that were cited by the 2891 manuscripts, and identified 676 top co-cited articles. Next, we used the bibliometric method, CiteSpace V, and VOSviewer 1.6.8 to identify top authors, journals, institutions, countries, keywords, co-cited articles, and trends.

We identified that the number of publications on gastrointestinal microbiome is increasing over time. 112 journals published articles on gastrointestinal microbiome. The United States of America was the leading country for publications, and the leading institution was the University of North Carolina. Co-cited reference analysis revealed the top landmark articles in the field. Gut microbiota, inflammatory bowel disease (IBD), probiotics, irritable bowel disease, and obesity are some of the high frequency keywords in co-occurrence cluster analysis and co-cited reference cluster analysis; indicating gut microbiota and related digestive diseases remain the hotspots in gut microbiome research. Burst detection analysis of top keywords showed that bile acid, obesity, and Akkermansia muciniphila were the new research foci.

This study revealed that our understanding of the link between gastrointestinal microbiome and associated diseases has evolved dramatically over time. The emerging new therapeutic targets in gut microbiota would be the foci of future research.

• Co-citation analysis
• Dysbiosis
• Gastrointestinal microbiome
• Research foci

• Autophagy
• Colitis
• Colorectal cancer
• IGF1R
• Insulin-like growth factor
• Metabolic syndrome

• Antibodies, Monoclonal/pharmacology
• Antibodies, Monoclonal/therapeutic use
• Autophagy
• Colitis/drug therapy
• Colitis/metabolism
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/etiology
• Colorectal Neoplasms/metabolism
• Humans
• Insulin-Like Growth Factor I/metabolism
• Metabolic Syndrome/complications
• Metabolic Syndrome/metabolism
• Receptor, IGF Type 1
• Receptors, Somatomedin/antagonists & inhibitors
• Receptors, Somatomedin/metabolism
• Signal Transduction/drug effects

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is associated with both genetic and environmental factors; however, the underlying pathogenesis of UC remains unclear. The present study aimed to further explore 12 microarray datasets from patients with UC obtained from the Gene Expression Omnibus repository, for potential genetic pathogenesis of UC through a global bioinformatics view, which included identification of differentially expressed genes (DEGs), functional enrichments, protein-protein interactions, transcriptional and post-transcriptional regulation and drug-gene associations. This integrated analysis screened 233 DEGs that were compared between UC and normal control tissue samples; these included 173 upregulated and 60 downregulated DEGs. Subsequently, transcription factors, such as TATA-binding protein 1 (TBP1; hsa_TATAAA_V$TATA_01) and nuclear factor-κB (NF-κB; hsa_V$NFKAPPAB_01) and microRNAs (miRNAs; such as miR-516-3p and miR-23a) were revealed to be associated with 233 DEGs. Notably, further analysis indicated that these DEGs were enriched in certain diseases, including inflammation, fibrosis and immune system diseases, and were also associated with some drugs, including prednisone, collagenase and mycophenolate mofetil, which may provide choice for treatment of UC. In conclusion, this study may provide novel insights into discovering potential molecular targets involved in the pathogenesis and treatment of UC.

• Inflammatory bowel disease
• microbiota
• probiotics
• ulcerative colitis

• JNK
• NF-κB
• Urotensin II antagonists
• neuropathic pain

• Animals
• Cytokines/metabolism
• Hyperalgesia/drug therapy
• Hyperalgesia/metabolism
• MAP Kinase Signaling System/drug effects
• Male
• NF-kappa B/antagonists & inhibitors
• Neuralgia/drug therapy
• Neuralgia/metabolism
• Physical Stimulation
• Rats
• Rats, Sprague-Dawley
• Sulfonamides/pharmacology
• Sulfonamides/therapeutic use
• Urotensins/antagonists & inhibitors

Baicalin is a bioactive ingredient extracted from the root of Scutellariae radix, which is used to treat ulcerative colitis (UC).

We investigated the activity of baicalin on lipopolysaccharide-stimulated RAW264.7 cells and 2,4,6-trinitrobenzene sulfonic acid-induced rats, including the attenuation of oxidant stress and apoptosis.

The severity of colitis was assessed by disease activity index. The activities of catalase (CAT), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), and the content of malondialdehyde (MDA) were determined by their corresponding kits. The terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) was performed to study whether experimental colitis was associated with intestinal epithelial cell (IEC) apoptosis and the effect of baicalin on IEC apoptosis. Western blot analysis and immunocytochemistry assay were applied to determine the protein expressions. The reactive oxygen species (ROS) level in the colon of UC rats treated with baicalin was determined by ROS assay kit.

Baicalin remarkably upregulated the activities of CAT, GSH-PX, and SOD and decreased the content of MDA in a dose-dependent manner in vitro and in vivo. The TUNEL-positive cells in rats treated baicalin were remarkably reduced. Both Western blot analysis and immunocytochemistry assay indicated that baicalin significantly decreased the expressions of transforming growth factor beta-1, Bax protein and upregulated the expression of Bcl-2 protein. In addition, the expressions of total and cleaved caspase-3, total and cleaved caspase-9 protein, Fas, and FasL in vitro were downregulated by the treatment with baicalin. Baicalin of different doses reduced the generation of ROS in UC rats.

Taken together, these evidences provide scientific basics for the application of baicalin in the treatment of UC and suggest that baicalin exerts its effect via suppression of oxidant stress and apoptosis.

Baicalin remarkably upregulated the activities of catalase, glutathione peroxidase, and superoxide dismutase and decreased the content of MDA, both in vivo and in vitro

Abbreviations used: UC: Ulcerative colitis, LPS: Lipopolysaccharide, TNBS: 2,4,6-trinitrobenzene sulfonic acid, DAI: Disease activity index, CAT: Catalase, GSH-PX: Glutathione peroxidase, SOD: Superoxide dismutase, MDA: Malondialdehyde, TUNEL: Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, ROS: Reactive oxygen species, IEC: Intestinal epithelial cell, SD: Sprague-Dawley, HE: H and E, DNTB: 5,5'-dithiobis-2-nitrobenzoic acid, TBA: Thiobarbituric acid, TBARS: Thiobarbituric acid-reactive substances, S.D: Standard deviation, and PBS: Phosphate-buffered saline.

• Apoptosis
• baicalin
• oxidative stress
• ulcerative colitis

Chronic diseases, such as obesity and diabetes, cardiovascular, and inflammatory bowel diseases (IBD) share common features in their pathology. Metabolic disorders exhibit strong inflammatory underpinnings and vice versa, inflammation is associated with metabolic alterations. Next to cytokines and cellular stress pathways, such as the unfolded protein response (UPR), alterations in the enteroendocrine system are intersections of various pathologies. Enteroendocrine cells (EEC) have been studied extensively for their ability to regulate gastrointestinal motility, secretion, and insulin release by release of peptide hormones. In particular, the L-cell-derived incretin hormone glucagon-like peptide 1 (GLP-1) has gained enormous attention due to its insulinotropic action and relevance in the treatment of type 2 diabetes (T2D). Yet, accumulating data indicate a critical role for EEC and in particular for GLP-1 in metabolic adaptation and in orchestrating immune responses beyond blood glucose control. EEC sense the lamina propria and luminal environment, including the microbiota via receptors and transporters. Subsequently, mediating signals by secreting hormones and cytokines, EEC can be considered as integrators of metabolic and inflammatory signaling. This review focuses on L cell and GLP-1 functions in the context of metabolic and inflammatory diseases. The effects of incretin-based therapies on metabolism and immune system are discussed and the interrelation and common features of metabolic and immune-mediated disorders are highlighted. Moreover, it presents data on the impact of inflammation, in particular of IBD on EEC and discusses the potential role of the microbiota as link between nutrients, metabolism, immunity, and disease.

• ER stress
• diabetes mellitus
• enteroendocrine cells
• glucagon-like peptide 1
• incretins
• inflammation
• inflammatory bowel disease
• microbiota

The interface between the intestinal lumen and the mucosa is the location where the majority of ingested immunogenic particles face the scrutiny of the vast gastrointestinal immune system. Upon regular physiological conditions, the intestinal micro-flora and the epithelial barrier are well prepared to process daily a huge amount of food-derived antigens and non-immunogenic particles. Similarly, they are ready to prevent environmental toxins and microbial antigens to penetrate further and interact with the mucosal-associated immune system. These functions promote the development of proper immune responses and oral tolerance and prevent disease and inflammation. Brain-gut axis structures participate in the processing and execution of response signals to external and internal stimuli. The brain-gut axis integrates local and distant regulatory networks and super-systems that serve key housekeeping physiological functions including the balanced functioning of the intestinal barrier. Disturbance of the brain-gut axis may induce intestinal barrier dysfunction, increasing the risk of uncontrolled immunological reactions, which may indeed trigger transient mucosal inflammation and gut disease. There is a large body of evidence indicating that stress, through the brain-gut axis, may cause intestinal barrier dysfunction, mainly via the systemic and peripheral release of corticotropin-releasing factor. In this review, we describe the role of stress and corticotropin-releasing factor in the regulation of gastrointestinal permeability, and discuss the link to both health and pathological conditions.

• Corticotropin-releasing factor
• Inflammation
• Permeability
• Stress

• Gut
• Inflammatory bowel disease
• Microbiota
• Prebiotic
• Probiotic

• Animals
• Colitis, Ulcerative/immunology
• Colitis, Ulcerative/microbiology
• Colitis, Ulcerative/therapy
• Crohn Disease/immunology
• Crohn Disease/microbiology
• Crohn Disease/therapy
• Humans
• Intestines/immunology
• Intestines/microbiology
• Microbiota
• Prebiotics
• Probiotics/therapeutic use
• Remission Induction
• Treatment Outcome

Defects in intestinal barrier function characterized by an increase in intestinal permeability contribute to intestinal inflammation. Growing evidence has shown that an increase in intestinal permeability has a pathogenic role in diseases such as inflammatory bowel disease (IBD) and celiac disease, and functional bowel disorders such as irritable bowel syndrome. Therefore, clarification of the inflammatory responses, the defense pathway and the corresponding regulatory system is essential and may lead to the development of new therapies. MicroRNAs (miRNAs) are small (19-22 nt) noncoding RNA molecules that regulate genes at the post-transcriptional level by base-pairing to specific messenger RNAs for degradation to repress translation. Recent studies suggested that miRNAs are important in the immune response and mediate a critical role in multiple immune response-related disorders. Based on these discoveries, attention has been focused on understanding the role of miRNAs in regulating intestinal barrier dysfunction, especially in IBD. Here, we provide a review of the most recent state-of-the-art research on miRNAs in intestinal barrier dysfunction.

• MicroRNAs
• Intestinal barrier dysfunction
• Inflammatory bowel disease
• Celiac disease
• Therapeutic target

• Autoimmune Diseases/metabolism
• Autophagy
• Gene Expression Regulation
• Humans
• Immune System
• Inflammation
• Inflammatory Bowel Diseases/therapy
• Intestinal Diseases/therapy
• Intestines/pathology
• MicroRNAs/metabolism
• MicroRNAs/therapeutic use
• Mitochondria/pathology
• RNA Processing, Post-Transcriptional
• Tight Junctions
• Treatment Outcome

• black raspberries
• wnt pathway
• methylation
• colon carcinogenesis
• il-10 ko mice

• Animals
• Colitis, Ulcerative/genetics
• Colitis, Ulcerative/metabolism
• Colitis, Ulcerative/prevention & control
• Colon/metabolism
• Colon/pathology
• DNA (Cytosine-5-)-Methyltransferases/genetics
• DNA (Cytosine-5-)-Methyltransferases/metabolism
• DNA Methylation
• DNA-Binding Proteins/genetics
• DNA-Binding Proteins/metabolism
• Diet
• Female
• Fruit/chemistry
• Histone Deacetylase 1/genetics
• Histone Deacetylase 1/metabolism
• Histone Deacetylase 2/genetics
• Histone Deacetylase 2/metabolism
• Humans
• Immunoenzyme Techniques
• Interleukin-10/physiology
• Mice
• Mice, Knockout
• Precancerous Conditions/genetics
• Precancerous Conditions/metabolism
• Precancerous Conditions/prevention & control
• Promoter Regions, Genetic/genetics
• RNA, Messenger/genetics
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Rosaceae/chemistry
• Sequence Analysis, DNA
• Wnt Signaling Pathway/genetics
• DNA Methyltransferase 3B

• R01 CA185301 NCI NIH HHS
• R01 ES017594 NIEHS NIH HHS
• U01 ES019482 NIEHS NIH HHS
• R01 CA103180 NCI NIH HHS
• P50 CA134254 NCI NIH HHS
• U54 CA113001 NCI NIH HHS
• R01 CA148818 NCI NIH HHS
• R01 CA069065 NCI NIH HHS
• R01 CA155521 NCI NIH HHS

• angiogenesis
• ibd
• tlr
• nlr

• vegetables
• fruit
• prevention
• chronic diseases
• epidemiology

• Animals
• Chronic Disease/prevention & control
• Evidence-Based Medicine
• Fruit
• Health Promotion
• Humans
• Vegetables

• Animals
• Apoptosis/drug effects
• Blotting, Western
• Colitis, Ulcerative/chemically induced
• Colitis, Ulcerative/drug therapy
• Colitis, Ulcerative/metabolism
• Dextran Sulfate/toxicity
• Epithelial Cells/cytology
• Epithelial Cells/drug effects
• Immunohistochemistry
• Iridoid Glucosides/therapeutic use
• Male
• NF-kappa B/metabolism
• Peroxidase/metabolism
• Plant Leaves/chemistry
• Rats
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction
• Signal Transduction/drug effects
• Syringa/chemistry

• Animals
• Crohn Disease/drug therapy
• Diterpenes/pharmacology
• Diterpenes/therapeutic use
• Drug Evaluation, Preclinical
• Epoxy Compounds/pharmacology
• Epoxy Compounds/therapeutic use
• Humans
• Interleukin-10/genetics
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Myeloid Differentiation Factor 88/antagonists & inhibitors
• Myeloid Differentiation Factor 88/metabolism
• Phenanthrenes/pharmacology
• Phenanthrenes/therapeutic use
• Phytotherapy
• Plant Extracts/pharmacology
• Plant Extracts/therapeutic use
• Signal Transduction/drug effects
• Tissue Culture Techniques
• Toll-Like Receptors/antagonists & inhibitors
• Toll-Like Receptors/metabolism
• Transcription Factor RelA/antagonists & inhibitors
• Transcription Factor RelA/metabolism
• Tripterygium

• Crohn’s disease
• arthralgia
• induction
• maintenance
• pouchitis
• remission
• sclerosing cholangitis
• spondyloartopathy
• ulcerative colitis