• efficacy
• functional gastrointestinal disorders
• irritable bowel syndrome
• prebiotics
• probiotics

• And recellularization
• Foreskin acellular matrix (FAM)
• Lactobacillus casei supernatant (LCS)
• Monophosphoryl lipid A (MPLA)

• Humans
• Mesenchymal Stem Cells/metabolism
• Lacticaseibacillus casei/metabolism
• Lipid A/metabolism
• Lipid A/analogs & derivatives
• Cell Movement/drug effects
• Skin/metabolism
• Tissue Scaffolds/chemistry
• Male
• Umbilical Cord/cytology
• Umbilical Cord/metabolism
• Foreskin/cytology
• Cell Transdifferentiation/drug effects
• Tissue Engineering/methods
• Extracellular Matrix/metabolism
• Keratin-19/metabolism
• Keratin-19/genetics

• 3653 Shahrekord University of Medical Sciences

• FODMAP
• IBS
• diet
• irritable bowel syndrome
• nutrition
• physical activity
• supplements

• Humans
• Nutritional Status
• Irritable Bowel Syndrome
• Exercise
• Nutritive Value
• Dietary Supplements

• Clostridioides difficile infection
• Gut microbiota
• Immunomodulation
• PPI
• Probiotics
• Proton pump inhibitors
• SIBO
• Salmonella infection

• N43/DBS/000190 Ministerstwo Edukacji i Nauki

• advantages of probiotics
• diagnosis of ibs
• irritable bowel syndrome
• probiotics rome
• treatment of ibs

• Anti-inflammatory effect
• Enterococcus durans
• Se-enrichment
• Transcriptome

• Caco-2 Cells
• Enterococcus
• Humans
• Inflammation/drug therapy
• Interleukin-8
• Lipopolysaccharides
• Membrane Proteins
• Nanoparticles/chemistry
• Probiotics/pharmacology
• Selenious Acid
• Selenium/analysis
• Sodium Selenite/pharmacology
• Tumor Necrosis Factor-alpha

• Giardia lamblia
• Conjugated linoleic acid
• IL-10
• Secretory IgA
• TGF-β

• IL-1β
• INFγ
• Prebiotic
• Probiotic
• TNFα
• Ulcerative colitis

• Humans
• Rats
• Animals
• Dextran Sulfate/toxicity
• Bacillus licheniformis
• Saccharomyces cerevisiae
• Sulfasalazine/adverse effects
• Synbiotics
• Rats, Sprague-Dawley
• Colitis/chemically induced
• Colitis/therapy
• Colitis/metabolism
• Colitis/veterinary

• Zagazig University

• Adult
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents/therapeutic use
• Child
• Humans
• Influenza Vaccines
• Influenza, Human
• Probiotics/therapeutic use
• Randomized Controlled Trials as Topic
• Respiratory Tract Infections/drug therapy
• Respiratory Tract Infections/prevention & control

• National Natural Science Foundation of China
• Natural Science Foundation of Gansu Province

The human gut symbiont Lacticaseibacillus (L.) casei (previously Lactobacillus casei) is under intense research due to its wide range of immunomodulatory effects on the human host. Dendritic cells (DCs) are crucial players in the direct and indirect communication with lactobacilli in the gastrointestinal tract. Here, we demonstrate that human monocyte-derived DCs (moDCs) are able to engulf L. casei BL23, in which the intact bacterial cell wall and morphology have a key role. The absence of the bacterial cell-wall-degrading enzyme, Lc-p75, in L. casei cells causes remarkable morphological changes, which have important consequences in the phagocytosis of L. casei by moDCs. Our results showed that the Lc-p75 mutation induced defective internalization and impaired proinflammatory and T-cell-polarizing cytokine secretion by bacteria-exposed moDCs. The T helper (Th) 1 and Th17 cell activating capacity of moDCs induced by the mutant L. casei was consequently reduced. Moreover, inhibition of the phagocytosis of wild-type bacteria showed similar results. Taken together, these data suggested that formation of short bacterial chains helps to exert the potent immunomodulatory properties of L. casei BL23.

• dendritic cells
• immunomodulation
• lactobacillus
• phagocytosis

Early postnatal events are important for the development of the neonatal immune system. Harboring the pioneering microorganisms forming the microbiota of the neonatal gastrointestinal tract is important for priming the immune system, as well as inducing appropriate tolerance to the relatively innocuous environmental antigens and compounds of normal healthy microbiota. Early postnatal supplementation of suitable, safe probiotics could accelerate this process. In the current study, the immunomodulatory capacity of the probiotic strain of Escherichia coli O83:K24:H31 (EcO83) was characterized in vitro and in vivo. We compared the capacity of EcO83 with and without hemolytic activity on selected immune characteristics in vitro as determined by flow cytometry and quantitative real-time PCR. Both strains with and without hemolytic activity exerted comparable capacity on the maturation of dendritic cells while preserving the induction of interleukin 10 (Il10) expression in dendritic cells and T cells cocultured with EcO83 primed dendritic cells. Early postnatal supplementation with EcO83 led to massive but transient colonization of the neonatal gastrointestinal tract, as detected by in vivo bioimaging. Early postnatal EcO83 administration promoted gut barrier function by increasing the expression of claudin and occludin and the expression of Il10. Early postnatal EcO83 application promotes maturation of the neonatal immune system and promotes immunoregulatory and gut barrier functions.

• Dendritic Cells
• Escherichia coli
• Humans
• Infant, Newborn
• Interleukin-10
• Microbiota
• Probiotics/pharmacology

• Milk
• Periodontitis
• Probiotic
• Rats
• Water

Three different types of lactic acid bacteria (Lactobacillus helveticus, Lactobacillus rhamnosus and Streptococcus thermophilus S₃₈₅₅) were used to manufacture white soft cheese. The resultant white soft cheeses were pickled for 28 days at refrigerator temperatures and were fed to the experimental rats. The chemical and microbiological analyses of white soft cheese were conducted at different storage periods (fresh, 7 days, 14 days, 21 days, and 28 days). The pH values and protein content of white soft cheese gradually decreased during the storage peroid. Conversely, the moisture content, titratable acidity, and fat/DM % of white soft cheese were found to increase with of the increase in pickling periods of up to 28 days. Microbiologically, the total viable count of bacteria in the control samples was lower than that in the other treatments. Furthermore, the treatments containing the L. helveticus and L. rhamnosus strains had the highest lactoacilli counts whereas the treatment containing the S. thermophilus strain had the highest streptococci counts. Twenty-five male Albino rats were used for experiemntal technique. Rats were fed with 70% basal diet with addition of 30% white soft cheese. Several pathological findings were present in all experimental groups apart from the control rats, and the kidney samples exhibited renal vascular congestion especially in the cortical area. The changes of the glomeruli comprise atrophy, distortion, hypocellularity of the glomerular tuft, and focal lymphoid cell reactions. The renal tubular epithelium showed a series of degenerative changes ranging up to necrosis. The liver samples showed variable hepatic injury in the form of thickening in the Glisson capsule, as well as dissociation and disorganization of hepatic cords. Hepatocellular vacuolar degeneration, presence of focal areas of nodular hyperplasia, the hyperplastic cells mixed with lymphocytic infiltration, congestion in the portal vein, periportal fibrosis and edema with the presence of newly formed nonfunctional bile ductulus. Based on the histopathology scores, the severity of renal and hepatic changes was significantly increased (P ≤ 0.05) in all of the experimental groups compared with the control group. Generally, the chemical composition, microbiological analysis and vital organs were significantly affected by using cultured white soft cheese.

• NK cell activity
• fructooligosaccharide
• galactooligosaccharide
• inulin
• inulin-type fructans
• respiratory tract infection
• xylooligosaccharide

• Adult
• Child
• Fatty Acids, Volatile
• Humans
• Immunity
• Infant
• Prebiotics
• Probiotics/therapeutic use
• Randomized Controlled Trials as Topic
• Respiratory Tract Infections/prevention & control
• Synbiotics

• Australian Government Research Training Program

To evaluate the probiotic characteristics and safety of Enterococcus durans isolate A8-1 from a fecal sample of a healthy Chinese infant, we determined the tolerance to low pH, survival in bile salts and NaCl, adhesion ability, biofilm formation, antimicrobial activity, toxin gene distribution, hemolysis, gelatinase activity, antibiotic resistance, and virulence to Galleria mellonella and interpreted the characters by genome resequencing. Phenotypically, E. durans A8-1 survived at pH 5.0 in 7.0% NaCl and 3% bile salt under aerobic and anaerobic condition. The bacterium had higher adhesion ability toward mucin, collagen, and Bovine Serum Albumin (BSA) in vitro and showed high hydrophobicity (79.2% in chloroform, 49.2% in xylene), auto-aggregation activity (51.7%), and could co-aggregate (66.2%) with Salmonella typhimurium. It had adhesion capability to intestinal epithelial Caco-2 cells (38.74%) with moderate biofilm production and antimicrobial activity against several Gram-positive pathogenic bacteria. A8-1 can antagonize the adhesion of S. typhimurium ATCC14028 on Caco-2 cells to protect the integrity of the cell membrane by detection of lactate dehydrogenase (LDH) and AKP activities. A8-1 also helps the cell relieve the inflammation induced by lipopolysaccharide by reducing the expression of cytokine IL-8 (P = 0.002) and TNF-α (P > 0.05), and increasing the IL-10 (P < 0.001). For the safety evaluation, A8-1 showed no hemolytic activity, no gelatinase activity, and had only asa1 positive in the seven detected virulence genes in polymerase chain reaction (PCR), whereas it was not predicted in the genome sequence. It was susceptible to benzylpenicillin, ampicillin, ciprofloxacin, levofloxacin, moxifloxacin, tigecycline, nitrofurantoin, linezolid, vancomycin, erythromycin, and quinupristin/dalofopine except clindamycin, which was verified by the predicted lasA, lmrB, lmrC, and lmrD genes contributing to the clindamycin resistance. The virulence test of G. mellonella showed that it had toxicity lower than 10% at 1 × 10⁷ CFU. According to the results of these evaluated attributes, E. durans strain A8-1 could be a promising probiotic candidate for applications.

• Enterococcus durans
• probiotic characters
• safety evaluation
• stress tolerance
• whole-genome sequencing

• immunology
• microbiome

Irritable bowel syndrome (IBS) is still a common functional gastrointestinal disease that presents chronic abdominal symptoms but with a pathophysiology that is not yet fully elucidated. Moreover, the use of the synergistic combination of prebiotics and probiotics, known as synbiotics, for IBS therapy is still in the early stages. Advancements in technology led to determining the important role played by probiotics in IBS, whereas the present paper focuses on the detailed review of the various pathophysiologic mechanisms of action of probiotics, prebiotics, and synbiotics via multidisciplinary domains involving the gastroenterology (microbiota modulation, alteration of gut barrier function, visceral hypersensitivity, and gastrointestinal dysmotility) immunology (intestinal immunological modulation), and neurology (microbiota–gut–brain axis communication and co-morbidities) in mitigating the symptoms of IBS. In addition, this review synthesizes literature about the mechanisms involved in the beneficial effects of prebiotics and synbiotics for patients with IBS, discussing clinical studies testing the efficiency and outcomes of synbiotics used as therapy for IBS.

• alternative therapy
• functional disease
• gut microbiota
• gut–brain axis

• Anxiety
• Brain/metabolism
• Comorbidity
• Depression
• Gastrointestinal Microbiome/physiology
• Gastrointestinal Motility
• Humans
• Intestinal Mucosa/metabolism
• Intestines/immunology
• Irritable Bowel Syndrome/diet therapy
• Irritable Bowel Syndrome/microbiology
• Irritable Bowel Syndrome/physiopathology
• Irritable Bowel Syndrome/psychology
• Prebiotics/administration & dosage
• Probiotics/therapeutic use
• Synbiotics/administration & dosage

COVID-19 pandemic continues to be a global health crisis. The gut microbiome critically affects the immune system, and some respiratory infections are associated with changes in the gut microbiome; here, we evaluated the role of nutritional and lifestyle habits that modulate gut microbiota on COVID-19 outcomes in a longitudinal cohort study that included 200 patients infected with COVID-19. Of these, 122 cases were mild and seventy-eight were moderate, according to WHO classification. After detailed explanation by a consultant in clinical nutrition, participants responded to a written questionnaire on daily sugar, prebiotic intake in food, sleeping hours, exercise duration and antibiotic prescription, during the past 1 year before infection. Daily consumption of prebiotic-containing foods, less sugar, regular exercise, adequate sleep and fewer antibiotic prescriptions led to a milder disease and rapid virus clearance. Additionally, data on these factors were compiled into a single score, the ESSAP score (Exercise, Sugar consumption, Sleeping hours, Antibiotics taken, and Prebiotics consumption; 0–11 points), median ESSAP score was 5 for both mild and moderate cases; however, the range was 4–8 in mild cases, but 1–6 in moderate (P = 0·001, OR: 4·2, 95 % CI 1·9, 9·1); our results showed a negative correlation between regular consumption of yogurt containing probiotics and disease severity (P = 0·007, OR: 1·6, 95 % CI 1·1, 2·1). Mild COVID-19 disease was associated with 10–20 min of daily exercise (P = 0·016), sleeping at least 8 h daily, prescribed antibiotics less than 5 times per year (P = 0·077) and ate plenty of prebiotic-containing food.

• COVID-19
• Exercise
• Gut microbiota
• Probiotics

• Lactobacillus plantarum
• VP7 gene
• immunization
• porcine rotavirus

The intestinal tract is a host to 100 trillion of microbes that have co-evolved with mammals over the millennia. These commensal organisms are critical to the host survival. The roles that symbiotic microorganisms play in the digestion, absorption, and metabolism of nutrients have been clearly demonstrated. Additionally, commensals are indispensable in regulating host immunity. This is evidenced by the poorly developed gut immune system of germ-free mice, which can be corrected by transplantation of specific commensal bacteria. Recent advances in our understanding of the mechanism of host–microbial interaction have provided the basis for this interaction. This paper reviews some of these key studies, with a specific focus on the effect of the microbiome on the immune organ development, nonspecific immunity, specific immunity, and inflammation.

• Gut microbiome
• Inflammation
• Nonspecific immunity
• Specific immunity

• Beneficial function
• gut barrier
• gut microbiota
• immune modulation
• lactic acid bacteria
• mechanism

Probiotics are known as “live microorganisms” and have been proven to have a health effect on hosts at the proper dose. Recently, a kind of probiotic mixture including eight live bacterial strains, VSL#3, has attracted considerable attention for its combined effect. VSL#3 is the only probiotic considered as a kind of medical food; it mainly participates in the regulation of the intestinal barrier function, including improving tight junction protein function, balancing intestinal microbial composition, regulating immune-related cytokine expression and so on. The objective of this review is to discuss the treatment action and mechanism for the administration of VSL#3 in chronic diseases of animals and humans (including children). We found that VSL#3 has a therapeutic or preventive effect in various systemic diseases per a large number of studies, including digestive systemic diseases (gastrointestinal diseases and hepatic diseases), obesity and diabetes, allergic diseases, nervous systemic diseases, atherosclerosis, bone diseases, and female reproductive systemic diseases.

• VSL#3
• Intestinal barrier function
• Chronic diseases
• Intestinal microbial balance
• Cytokines
• Therapeutic use

• Helicobacter pylori
• IFN-γ
• IL-10
• Lactobacillus spp.
• T-regulatory cells
• adaptive immune response
• dendritic cells

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a complex etiology involving the immune response. Recent studies have demonstrated the role of certain probiotics in the treatment and prevention of AD. However, the mechanism by which these probiotics regulate the immune system remains unclear. In this study, we examined the immunomodulatory capacity of Duolac ATP, a mixed formulation of probiotics, both in vitro and in vivo. Results showed that the expression of programmed death-ligand 1(PD-L1) was significantly upregulated on bone marrow-derived dendritic cells (BMDCs) treated with Duolac ATP. Furthermore, the anti-inflammatory cytokines IL-10 and TGF-beta were both upregulated when BMDCs were treated with Duolac ATP. The percentage of proliferated regulatory T cells (Tregs) was enhanced when CD4⁺ T cells were co-cultured with Duolac ATP-treated BMDCs on plates coated with anti-CD3/CD28 antibodies. Intriguingly, IL-10 secretion from CD4⁺ T cells was also observed. The AD symptoms, histologic scores, and serum IgE levels in AD mice were significantly decreased after oral treatment with Duolac ATP. Moreover, the Th1-mediated response in AD-induced mice treated with oral Duolac ATP showed upregulation of IL-2 and IFN-gamma as well as of downstream signaling molecules T-bet, STAT-1, and STAT-4. Conversely, Duolac ATP suppressed Th2 and Th17 responses in AD-like mice, as evidenced by the downregulation of GATA-3, C-maf, IL-4, IL-5, and IL-17. Additionally, Duolac ATP increased the number of Tregs found at Peyer’s patches (PP) in treated AD mice. These results suggest that Duolac ATP modulates DCs to initiate both Th1 and Treg responses in AD mice. Thus, Duolac ATP represents a potential preventative agent against AD and could serve as an effective immunomodulator in AD patients.

• T cell balances
• atopic dermatitis
• dendritic cell
• health food
• probiotics

• allergy
• immune system
• microbiota
• probiotics

• Adipokines
• Adipose tissue
• Chronic low-grade inflammation
• Metabolic syndrome
• Obesity
• Probiotics

Lactobacillus (LAB) have been reported to exert both harmful and beneficial effects on human and animal health. Recently, it has been reported that dysbiosis and bacterial translocation contribute to liver fibrosis. However, the role of Gram-positive LAB in the situation of chronic liver diseases has not been yet elucidated. Liver injury was induced by bile duct ligation (BDL) in LAB or control-administered mice. Liver fibrosis was enhanced in LAB-administered mice compared with control-treated mice as demonstrated by quantification of Sirius-red positive area, hydroxyproline contents and fibrosis-related genes (Col1α1, Acta2, Timp1, Tgfb1). Moreover, LAB-administered mice were more susceptible to BDL-induced liver injury as shown by increased ALT and AST level of LAB group compared with control group at 5 days post BDL. Consistent with serum level, inflammatory cytokines (TNF-α, IL-6 and IL-1β) were also significantly increased in LAB-treated mice. Of note, LAB-treated liver showed increased lipoteichoic acid (LTA) expression compared with control-treated liver, indicating that LAB-derived LTA may translocate from intestine to liver via portal vein. Indeed, responsible receptor or inflammatory factor (PAFR and iNOS) for LTA were upregulated in LAB-administered group. The present findings demonstrate that administration of LAB increases LTA translocation to liver and induces profibrogenic inflammatory milieu, leading to aggravation of liver fibrosis. The current study provides new cautious information of LAB for liver fibrosis patients to prevent the detrimental effect of LAB supplements.

• LAB
• LTA
• Liver fibrosis

Goose parvovirus (GPV) continues to be a threat to goose farms and has significant economic effects on the production of geese. Current commercially available vaccines only rarely prevent GPV infection. In our study, Lactobacillus (L.) plantarum NC8 was selected as a vector to express the VP2 gene of GPV, and recombinant L. plantarum pSIP409-VP2/NC8 was successfully constructed. The molecular weight of the expressed recombinant protein was approximately 70 kDa. Mice were immunized with a 2 × 10⁹ colony-forming unit/200 µL dose of the recombinant L. plantarum strain, and the ratios and numbers of CD11c⁺, CD3⁺CD4⁺, CD3⁺CD8⁺, and interferon gamma- and tumor necrosis factor alpha-expressing spleen lymphocytes in the pSIP409-VP2/NC8 group were higher than those in the control groups. In addition, we assessed the capacity of L. plantarum SIP409-VP2/NC8 to induce secretory IgA production. We conclude that administered pSIP409-VP2/NC8 leads to relatively extensive cellular responses. This study provides information on GPV infection and offers a clear framework of options available for GPV control strategies.

• Lactobacillus plantarum
• VP2 gene
• goose parvovirus
• immunization

• Autoimmunity
• CD8(+) T cells
• Immune regulation
• Prebiotics
• Probiotics
• Regulatory T cells

• Autoimmunity/immunology
• Humans
• Immune Tolerance
• Lymphocyte Activation
• Prebiotics
• Probiotics
• T-Lymphocytes, Regulatory/immunology

• Lactobacillus
• Saccharomyces
• bacteremia
• probiotics
• safety

• Cytokines
• Innate immunity
• Lactobacilli
• Macrophages
• Nitric oxide
• Phagocytosis

• Lactococcus lactis
• colitis
• lysozyme
• oxidative stress
• probiotics

AIM: To investigate the change in intestinal dendritic cell (DC) number in fulminant hepatic failure (FHF).

METHODS: An animal model of FHF was created. Intestinal CD11b/c was detected by immunohistochemistry and Western blot. Quantitative real-time polymerase chain reaction (PCR) was used to detect intestinal integrin-α mRNA expression. Intestinal CD83, CD86, CD74, CD3 and AKT were detected by immunohistochemistry, Western blot and PCR. Phosphorylated-AKT (p-AKT) was detected by immunohistochemistry and Western blot.

RESULTS: In the FHF group [D-galactosamine (D-Galn) + lipopolysaccharide (LPS) group], the mice began to die after 6 h; conversely, in the D-Galn and LPS groups, the activity of mice was poor, but there were no deaths. Immunohistochemistry results showed that in FHF, the expression of CD11b/c (7988400 ± 385941 vs 1102400 ± 132273, P < 0.05), CD83 (13875000 ± 467493 vs 9257600 ± 400364, P < 0.05), CD86 (7988400 ± 385941 vs 1102400 ± 13227, P < 0.05) and CD74 (11056000 ± 431427 vs 4633400 ± 267903, P < 0.05) was significantly increased compared with the normal saline (NS) group. Compared with the NS group, the protein expression of CD11b/c (5.4817 ± 0.77 vs 1.4073 ± 0.37, P < 0.05) and CD86 (4.2673 ± 0.69 vs 1.1379 ± 0.42, P < 0.05) was significantly increased. Itg-α (1.1224 ± 0.3 vs 0.4907 ± 0.19, P < 0.05), CD83 (3.6986 ± 0.40 vs 1.0762 ± 0.22, P < 0.05) and CD86 (1.5801 ± 0.32 vs 0.8846 ± 0.10, P < 0.05) mRNA expression was increased significantly in the FHF group. At the protein level, expression of CD74 in the FHF group (2.3513 ± 0.52) was significantly increased compared with the NS group (1.1298 ± 0.33), whereas in the LPS group (2.3891 ± 0.47), the level of CD74 was the highest (P < 0.05). At the gene level, the relative expression of CD74 mRNA in the FHF group (1.5383 ± 0.26) was also significantly increased in comparison to the NS group (0.7648 ± 0.22; P < 0.05). CD3 expression was the highest in the FHF group (P < 0.05). In the FHF, LPS and D-Galn groups, the expression of AKT at the protein and mRNA levels was elevated compared with the NS group, but there was no statistical significance (P > 0.05). The p-AKT protein expression in the FHF (1.54 ± 0.06), LPS (1.56 ± 0.05) and D-Galn (1.29 ± 0.03) groups was higher than that in the NS group (1.07 ± 0.03) (P < 0.05).

CONCLUSION: In FHF, a large number of DCs mature, express CD86, and activate MHC class II molecular pathways to induce a T cell response, and the AKT pathway is activated.

• Fulminant hepatic failure
• Intestinal dendritic cells
• MHC II
• CD3
• AKT/Phosphorylated-AKT

• Animals
• Antigens, Differentiation, B-Lymphocyte/metabolism
• B7-2 Antigen/metabolism
• Biomarkers/metabolism
• CD11b Antigen/metabolism
• CD11c Antigen/metabolism
• CD3 Complex/metabolism
• Cell Communication
• Cell Count
• Dendritic Cells/immunology
• Dendritic Cells/metabolism
• Dendritic Cells/pathology
• Disease Models, Animal
• Histocompatibility Antigens Class II/metabolism
• Intestinal Mucosa/metabolism
• Intestines/immunology
• Intestines/pathology
• Liver Failure, Acute/immunology
• Liver Failure, Acute/metabolism
• Liver Failure, Acute/pathology
• Lymphocyte Activation
• Mice, Inbred BALB C
• Phosphorylation
• Proto-Oncogene Proteins c-akt/metabolism
• Signal Transduction
• T-Lymphocytes/immunology
• T-Lymphocytes/metabolism

• crosstalk bacteria-host
• human health
• immunomodulation
• microbiota

• Acute Disease
• Adult
• Aged
• Child
• Female
• Humans
• Male
• Probiotics/therapeutic use
• Randomized Controlled Trials as Topic
• Respiratory Tract Infections/prevention & control

The potential for the positive manipulation of the gut microbiome through the introduction of beneficial microbes, as also known as probiotics, is currently an active area of investigation. The FAO/WHO define probiotics as live microorganisms that confer a health benefit to the host when administered in adequate amounts. However, dead bacteria and bacterial molecular components may also exhibit probiotic properties. The results of clinical studies have demonstrated the clinical potential of probiotics in many pathologies, such as allergic diseases, diarrhea, inflammatory bowel disease and viral infection. Several mechanisms have been proposed to explain the beneficial effects of probiotics, most of which involve gene expression regulation in specific tissues, particularly the intestine and liver. Therefore, the modulation of gene expression mediated by probiotics is an important issue that warrants further investigation. In the present paper, we performed a systematic review of the probiotic-mediated modulation of gene expression that is associated with the immune system and inflammation. Between January 1990 to February 2014, PubMed was searched for articles that were published in English using the MeSH terms “probiotics" and "gene expression" combined with “intestines", "liver", "enterocytes", "antigen-presenting cells", "dendritic cells", "immune system", and "inflammation". Two hundred and five original articles matching these criteria were initially selected, although only those articles that included specific gene expression results (77) were later considered for this review and separated into three major topics: the regulation of immunity and inflammatory gene expression in the gut, in inflammatory diseases of the gut and in the liver. Particular strains of Bifidobacteria, Lactobacilli, Escherichia coli, Propionibacterium, Bacillus and Saccharomyces influence the gene expression of mucins, Toll-like receptors, caspases, nuclear factor-κB, and interleukins and lead mainly to an anti-inflammatory response in cultured enterocytes. In addition, the interaction of commensal bacteria and probiotics with the surface of antigen-presenting cells in vitro results in the downregulation of pro-inflammatory genes that are linked to inflammatory signaling pathways, whereas other anti-inflammatory genes are upregulated. The effects of probiotics have been extensively investigated in animal models ranging from fish to mice, rats and piglets. These bacteria induce a tolerogenic and hyporesponsive immune response in which many genes that are related to the immune system, in particular those genes expressing anti-inflammatory cytokines, are upregulated. By contrast, information related to gene expression in human intestinal cells mediated by the action of probiotics is scarce. There is a need for further clinical studies that evaluate the mechanism of action of probiotics both in healthy humans and in patients with chronic diseases. These types of clinical studies are necessary for addressing the influence of these microorganisms in gene expression for different pathways, particularly those that are associated with the immune response, and to better understand the role that probiotics might have in the prevention and treatment of disease.

• Gene expression
• Immunity
• Immunotolerance
• Inflammation
• Microbiota
• Probiotics
• Gut
• Liver

• Animals
• Bacteria/immunology
• Bacteria/metabolism
• Disease Models, Animal
• Gene Expression Regulation
• Host-Pathogen Interactions
• Humans
• Inflammation Mediators/immunology
• Inflammation Mediators/metabolism
• Inflammatory Bowel Diseases/genetics
• Inflammatory Bowel Diseases/immunology
• Inflammatory Bowel Diseases/metabolism
• Inflammatory Bowel Diseases/microbiology
• Inflammatory Bowel Diseases/therapy
• Intestinal Mucosa/metabolism
• Intestines/immunology
• Intestines/microbiology
• Liver/immunology
• Liver/metabolism
• Liver/microbiology
• Liver Diseases/genetics
• Liver Diseases/immunology
• Liver Diseases/metabolism
• Liver Diseases/microbiology
• Liver Diseases/therapy
• Probiotics/therapeutic use

• Crohn’s disease
• Inflammatory bowel disease
• M1
• M2
• Probiotic
• Ulcerative colitis
• VSL#3
• macrophage

• R25 GM082406 NIGMS NIH HHS
• U54 MD007579 NIMHD NIH HHS
• U54 RR026139 NCRR NIH HHS
• U54 MD007587 NIMHD NIH HHS
• G12 MD007579 NIMHD NIH HHS
• U54 CA163071 NCI NIH HHS
• G12 RR003050 NCRR NIH HHS

Previous findings suggested that Lactobacillus rhamnosus CRL1505 is able to increase resistance of children to intestinal viral infections. However, the intestinal cells, cytokines and receptors involved in the immunoregulatory effect of this probiotic strain have not been fully characterized.

We aimed to gain insight into the mechanisms involved in the immunomodulatory effect of the CRL1505 strain and therefore evaluated in vitro the crosstalk between L. rhamnosus CRL1505, porcine intestinal epithelial cells (IECs) and antigen presenting cells (APCs) from swine Peyer’s patches in order to deepen our knowledge about the mechanisms, through which this strain may help preventing viral diarrhoea episodes. L. rhamnosus CRL1505 was able to induce IFN–α and –β in IECs and improve the production of type I IFNs in response to poly(I:C) challenge independently of Toll-like receptor (TLR)-2 or TLR9 signalling. In addition, the CRL1505 strain induced mRNA expression of IL-6 and TNF-α via TLR2 in IECs. Furthermore, the strain significantly increased surface molecules expression and cytokine production in intestinal APCs. The improved Th1 response induced by L. rhamnosus CRL1505 was triggered by TLR2 signalling and included augmented expression of MHC-II and co-stimulatory molecules and expression of IL-1β, IL-6, and IFN-γ in APCs. IL-10 was also significantly up-regulated by CRL1505 in APCs.

It was recently reviewed the emergence of TLR agonists as new ways to transform antiviral treatments by introducing panviral therapeutics with less adverse effects than IFN therapies. The use of L. rhamnosus CRL1505 as modulator of innate immunity and inductor of antiviral type I IFNs, IFN-γ, and regulatory IL-10 clearly offers the potential to overcome this challenge.

• Humans
• Inflammatory Bowel Diseases/diet therapy
• Probiotics/therapeutic use
• Randomized Controlled Trials as Topic
• Remission Induction

Subpopulations of peripheral leukocytes and cytokine mRNA expression levels were evaluated in scouring and healthy Holstein calves (age 10 ± 5 days; n=42) treated with a probiotic consisting of Lactobacillus plantarum, Enterococcus faecium and Clostridium butyricum. The calves were assigned to the scouring or healthy group and then subdivided into pathogen-positive treated (n=8), pathogen-positive control (n=8), pathogen-negative treated (n=6), pathogen-negative control (n=6), healthy treated (n=6) and healthy control (n=8) groups. A single dose of the probiotic (3.0 g/100 kg body weight) was given to each calf in the treatment groups for 5 days. Blood samples were collected on the first day of scour occurrence (day 0) and on day 7. In the scouring calves, smaller peripheral leukocyte subpopulations and cytokine mRNA expression levels were noted on day 0. The numbers of CD3⁺ T cells; CD4⁺, CD8⁺ and WC1⁺ γδ T cell subsets; and CD14⁺, CD21⁺ and CD282⁺ (TLR2) cells were significantly increased in the scouring and healthy treated calves on day 7. Furthermore, interleukin-6, tumor necrosis factor-alpha and interferon-gamma mRNA expression was elevated in the peripheral leukocytes of the scouring and healthy treated calves on day 7. The scouring calves given the probiotic recovered on day 7. A significantly smaller number of peripheral leukocytes and lower cytokine mRNA expression level might be induced by scouring in calves. Repeated probiotic administration might stimulate cellular immunity and encourage recovery from scouring in pre-weaning Holstein calves.

The intestinal mucosa plays a critical role in the host’s interactions with innocuous commensal microbiota and invading pathogenic microorganisms. Intestinal epithelial cells (IECs) and gut associated immune cells recognize the bacterial components via pattern-recognition receptors (PRRs) and are responsible for maintaining tolerance to the large communities of resident luminal bacteria while being also able to mount inflammatory responses against pathogens. Toll-like receptors (TLRs) are a major class of PRRs that are present on IECs and immune cells which are involved in the induction of both tolerance and inflammation. A growing body of experimental and clinical evidence supports the therapeutic and preventive application of probiotics for several gastrointestinal inflammatory disorders in which TLRs exert a significant role. This review aims to summarize the current knowledge of the beneficial effects of probiotic microorganisms with the capacity to modulate the immune system (immunobiotics) in the regulation of intestinal inflammation in pigs, which are very important as both livestock and human model. Especially we discuss the role of TLRs, their signaling pathways, and their negative regulators in both the inflammatory intestinal injury and the beneficial effects of immunobiotics in general, and Lactobacillus jensenii TL2937 in particular. This review article emphasizes the cellular and molecular interactions of immunobiotics with IECs and immune cells through TLRs and their application for improving animal and human health.

• Lactobacillus jensenii TL2937, TLR4
• immunobiotics
• inflammation
• intestinal immunity