lactoferrin and Intestinal-Diseases

The gastrointestinal tract may be viewed as an ecologic system in which a balance between the host and bacterial flora exists. Two major host components appear to be involved in maintaining this balance. The first is a non-specific structural barrier provided by the epithelial layer of the gastrointestinal mucosae. The second component involves functional immunological elements found in the mucosal and submucosal compartments, e.g., gut associated lymphoid tissue. When gut integrity is disrupted by invasive pathogens or by trauma, a myriad of pro-inflammatory mediators are released from cells in the gut wall that exert actions in the tissue or gut lumen. One of these mediators is lactoferrin, and iron binding protein found in high concentration in most human exocrine secretions. Despite controversies on its physiological role, evidence is emerging that lactoferrin plays an important role in host defense against toxic metabolites and antigenic components of potential pathogens2-4. This manuscript is intended to provide an overview of work related to lactoferrin's modulatory roles in inflammation, and to present observations from experimental studies on the preservation of intestinal structure and function by lactoferrin during intestinal inflammation. The possibility that lactoferrin limits the autodestructive inflammatory responses presents a new alternative for the future management of systemic inflammation.

Topics: Animals; Humans; Inflammation; Intestinal Diseases; Lactoferrin; Mice

Topics: Administration, Oral; Animals; Bacterial Infections; Bacterial Vaccines; Gastric Acid; Humans; Immunity, Cellular; Immunity, Innate; Immunization, Passive; Immunoglobulin A; Interferons; Intestinal Diseases; Intestinal Diseases, Parasitic; Intestinal Mucosa; Intestines; Lactoferrin; Muramidase; Vaccination; Vaccines; Vaccines, Attenuated

The impact of lactoferrin, an antimicrobial peptide (AMP) with iron-binding properties, on the intestinal barrier and microflora of mice infected with highly pathogenic avian influenza A (H5N1) virus remains unclear. To investigate the effects of lactoferrin on the histopathology and intestinal microecological environment, we conducted a study using H5N1-infected mice. H5N1 infection resulted in pulmonary and intestinal damage, as well as an imbalance in gut microbiota, significantly increasing the abundance of pathogenic bacteria such as

Topics: Animals; Bacteria; Gastrointestinal Microbiome; Inflammation; Influenza A Virus, H5N1 Subtype; Intestinal Diseases; Intestines; Lactoferrin; Mice

Deoxynivalenol (DON) is a major mycotoxin present in staple foods (particularly in cereal products) that induces intestinal inflammation and disrupts intestinal integrity. Lactoferrin (LF) is a multifunctional protein that contributes to maintaining intestinal homeostasis and improving host health. However, the protective effects of LF on DON-induced intestinal dysfunction remain unclear.. This study aimed to investigate the effects of LF on DON-induced intestinal dysfunction in mice, and its underlying protective mechanism.. Male BALB/c mice (5 wk old) with similar body weights were divided into 4 groups (n = 6/group) and treated as follows for 5 wk: Veh [peroral vehicle daily, commercial (C) diet]; LF (peroral 10 mg LF/d, C diet); DON (Veh, C diet containing 12 mg DON/kg); and LF + DON (peroral 10 mg LF/d, DON diet). Intestinal morphology, tight junction proteins, cytokines, and microbial community were determined. Data were analyzed by 2-factor ANOVA or Kruskal-Wallis test.. The DON group exhibited lower final body weight (-12%), jejunal villus height (VH; -41%), and jejunal occludin expression (-36%), and higher plasma IL-1β concentration (+85%) and jejunal Il1b mRNA expression (+98%) compared with the Veh group (P < 0.05). In contrast, final body weight (+19%), jejunal VH (+49%), jejunal occludin (+53%), and intelectin 1 protein expression (+159%) were greater in LF + DON compared with DON (P < 0.05). Additionally, jejunal Il1b mRNA expression (-31%) and phosphorylation of p38 and extracellular signal regulated kinase 1/2 (-40% and - 38%) were lower in LF + DON compared with DON (P < 0.05). Furthermore, the relative abundance of Clostridium XIVa (+181%) and colonic butyrate concentration (+53%) were greater in LF + DON compared with DON (P < 0.05).. Our study highlights a promising antimycotoxin approach using LF to alleviate DON-induced intestinal dysfunction by modulating the mitogen-activated protein kinase pathway and gut microbial community in mice.

Topics: Animals; Gastrointestinal Microbiome; Inflammation; Intestinal Diseases; Lactoferrin; Male; MAP Kinase Signaling System; Mice; Occludin; RNA, Messenger; Trichothecenes

Nonsteroidal anti-inflammatory drugs can exert detrimental effects in the lower digestive tract. The aim of this study was to examine the protective effects of a combination of the probiotic Bifidobacterium longum BB536 (Bifidobacterium) with the prebiotic lactoferrin in a rat model of diclofenac-induced enteropathy.. Diclofenac induced intestinal damage, along with increments of MPO and MDA, overexpression of TLR-2, TLR-4, MyD88, and NF-κB p65, increased fecal calprotectin and decreased blood hemoglobin levels. Lactoferrin or Bifidobacterium alone prevented diclofenac-induced enteric damage, and the changes in blood hemoglobin, MPO, MDA, fecal calprotectin, and NF-κB p65. Bifidobacterium, but not lactoferrin, decreased TLR-4 expression, although none of them affected MyD88 overexpression. TLR-2 expression was slightly enhanced by all treatments. The combined administration of lactoferrin and Bifidobacterium reduced further the intestinal damage, and restored MPO and blood hemoglobin levels.. Diclofenac induced ileal mucosal lesions by activation of inflammatory and pro-oxidant mechanisms. These detrimental actions were prevented by the combination of lactoferrin with Bifidobacterium likely through the modulation of TLR-2/-4/NF-κB proinflammatory pathways.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bifidobacterium longum; Diclofenac; Feces; Hemoglobins; Ileum; Intestinal Diseases; Intestinal Mucosa; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Malondialdehyde; NF-kappa B; Peroxidase; Prebiotics; Probiotics; Protective Agents; Rats; Signal Transduction; Toll-Like Receptor 2; Toll-Like Receptor 4

Small intestinal lesions in patients with Behçet disease (BD) have a risk of perforation and hemorrhage requiring surgery. However, no screening strategy for such lesions has been established. We investigated small intestinal lesions in BD patients with video capsule endoscopy (VCE) and analyzed clinical characteristics to identify noninvasive biomarkers of such lesions.. This study included 33 BD patients who underwent VCE (PillCam® SB3) at our institution from June 2016 to January 2019. Clinical characteristics, including age, sex, disease duration, body mass index, gastrointestinal symptoms, eye involvement, and blood examinations, were obtained from the medical records of 27 of the 33 patients. Fecal immunochemical tests for hemoglobin, fecal calprotectin (FC), and fecal lactoferrin (FL) were measured. VCE findings of 145 healthy Japanese individuals from a previous report were used as controls.. Two intestinal BD patients were included in the 27 patients. We observed that BD patients exhibit more small intestinal lesions compared with healthy individuals, including erosions, ulcers, and total lesions (erosions or ulcers). FC and FL levels were significantly higher in patients with versus without small intestinal lesions (P = 0.034 and P = 0.046, respectively). Receiver operating characteristic analyses demonstrated that FC (cutoff value = 119 μg/g) and FL (cutoff value = 17 μg/g) were biomarkers for small intestinal lesions in patients with BD.. The present study using VCE showed that patients with BD had more small intestinal lesions than healthy individuals. FC and FL could be useful for screening BD patients who may have small intestinal lesions.

Topics: Adolescent; Adult; Behcet Syndrome; Biomarkers; Capsule Endoscopy; Feces; Female; Humans; Intestinal Diseases; Intestine, Small; Lactoferrin; Leukocyte L1 Antigen Complex; Male; Middle Aged; Risk Factors; ROC Curve; Young Adult

Lactoferricin (Lfcin) B, derived from lactoferrin in whey, has attracted considerable attention because of its multiple biological functions. Zoonotic enterohemorrhagic Escherichia coli (EHEC) O157:H7 has adverse effects on intestinal epithelial barrier function, leading to serious intestinal disease. In this study, the EHEC O157:H7-induced intestinal dysfunction model was developed to investigate the effects of Lfcin B on EHEC O157:H7-induced epithelial barrier disruption and microbiota dysbiosis. Results showed that the inflammatory infiltration indexes in the jejunum of Lfcin B-treated animals were significantly decreased. Lfcin B administration also significantly improved ZO-1 and occludin expression following O157:H7-induced injury. Finally, microbiota analysis of the cecal samples revealed that Lfcin B inhibited the O157:H7-induced abnormal increase in Bacteroides. Therefore, Lfcin B efficiently attenuated O157:H7-induced epithelial barrier damage and dysregulation of inflammation status, while maintaining microbiota homeostasis in the intestine, indicating that it may be an excellent food source for prevention and therapy of EHEC O157:H7-related intestinal dysfunction.

Topics: Administration, Oral; Animals; Bacteria; Cattle; Escherichia coli Infections; Escherichia coli O157; Gastrointestinal Microbiome; Humans; Intestinal Diseases; Lactoferrin; Male; Mice; Mice, Inbred C57BL

Fecal calprotectin and lactoferrin are sensitive markers of mucosal inflammation. We compared three different assays in their ability to identify patients with organic intestinal disease.. In a post-hoc analysis of a prospective study, we examined 405 unselected patients with abdominal complaints referred for endoscopy to the University Hospital Basel, Switzerland. Calprotectin (EK-CAL, Bühlmann Laboratories, Switzerland; PhiCal, Calpro AS, Norway) and lactoferrin (IBD-Scan, Techlab, USA) were measured using enzyme-linked immunosorbent assays. The presence of a clinically significant endoscopic finding was the primary endpoint of the study. Final diagnoses were adjudicated blinded to calprotectin values.. The prevalence of organic intestinal disease was 35.3%. Receiver operating characteristics analysis calculated an area under the curve (AUC) for EK-CAL of 0.918, which was significantly better than for PhiCal (AUC 0.842, P<0.001) and IBD-Scan (AUC 0.830, P=0.003) to identify patients with organic intestinal disease. Overall test accuracy was 88.1% for EK-CAL, 83.7% for PhiCal, and 81.3% for IBD-Scan. Optimal cut-off value calculated for PhiCal and IBD-Scan were lower than recommended by the manufacturer.. Monoclonal testing of calprotectin is superior to both polyclonal calprotectin testing and fecal lactoferrin in identifying symptomatic patients with organic intestinal disease.

Topics: Adult; Antibodies; Antibodies, Monoclonal; Biomarkers; Enzyme-Linked Immunosorbent Assay; Feces; Humans; Intestinal Diseases; Lactoferrin; Leukocyte L1 Antigen Complex; Prospective Studies; ROC Curve; Switzerland

Increased intestinal permeability has been advocated as one of the likely causes of various pathologies, such as allergies and metabolic or even cardiovascular disturbances. Thus, the aim of the present study was to test a symbiotic preparation containing microbial lysates (KC-1317, Named, Italy) against stress-induced derangement of gut mucosa permeability. Sprague Dawley rats were allocated into control (n=20) and stress (n=20) group. Stress was implemented by 1h of water avoidance stress daily for 10 days. Body weight, food and water intake and passage of stool pellet during stress session were recorded throughout the experiment. On the 11th day, fluorescent iso-thiocyanate dextran solution was injected into small intestinal loops. One hour after the injection, rats were sacrificed. Jejunum and ileum were taken for histopathology. Blood was collected from the abdominal aorta to measure intestinal permeability. In stress group, stool pellets during stress session was significantly higher than control group (p < 0.01). Villus height (p < 0.01), crypt depth (p < 0.01), number of goblet cells in villus (p < 0.01) and crypt (p < 0.05) decreased significantly in jejunum as compared to control. These phenomena were significantly prevented by KC-1317 (p < 0.05). Ileum also showed atrophy but villus height and the number of goblet cells in the villi did not significantly differ. Plasma-concentration of brain-gut peptides (substance P, thyrotropin-releasing hormone, cholecystokinin and motilin) were affected by stress (p < 0.001) and this effect did not change during supplementation with KC-1317. Polymorphonuclear neutrophil counting was significantly higher in stress group as compared to control (p < 0.01) but this phenomenon was abolished in the ileum (p < 0.01) or partly but significantly reduced by KC-1317 supplementation (p < 0.05). Accordingly, intestinal permeability was significantly enhanced in stress group as compared to control (p < 0.01) and prevented by KC-1317 (p < 0.01) in both intestinal segments examined. While confirming that chronic mild stress in rats compromises small intestinal morphology and permeability, we showed that a symbiotic microbial lysate can partly counteract this phenomenon.

Topics: Animals; Anti-Infective Agents; Fragaria; Ileum; Intestinal Absorption; Intestinal Diseases; Intestinal Mucosa; Jejunum; Lactoferrin; Lactose; Male; Probiotics; Rats; Rats, Sprague-Dawley; Saccharomyces; Stress, Psychological; Vaccinium macrocarpon

Intestinal ischemia-reperfusion (I/R) is a common and serious clinical condition. Lactoferrin (Lf) has displayed antioxidative and anti-inflammatory activities in protecting the intestinal mucosa. The objective of this study was to investigate whether oral administration of Lf could attenuate I/R-induced intestinal injury.. The experimental design consisted of three groups of Wistar rats (24 per group): sham operation, control (I/R, saline), Lf (I/R, Lf). Intestinal I/R was produced by occlusion of the superior mesenteric artery for 45 min. Eight rats from each group were randomly sacrificed 3, 12 or 36 h after reperfusion, and blood and intestinal samples were collected.. Intestinal I/R resulted in gut damage evidenced by morphological alteration, reduction of γ-glutamyl transpeptidase (γ-GGT) activity and increased cell apoptosis. Daily administration of Lf (200 mg/kg) for 14 days before surgery significantly attenuated gut damage by reducing the histologic score and apoptosis index, and restoring intestinal γ-GGT activity. Lf reduced intestinal malondialdehyde and myeloperoxidase, restored glutathione and decreased serum levels of tumor necrosis factor-α, interleukin (IL)-1β and IL-6 compared with saline control in I/R rats. In addition, oral administration of Lf did not produce any significant effects in healthy rats; Lf at doses of 50 or 100 mg/kg also attenuated I/R-induced gut damage, but administration of Lf for 7 days did not exert a significant protective effect against I/R-induced gut damage.. These results indicate that Lf may serve as a potent supplement in protecting the gut from intestinal I/R-induced injury by its antioxidative, anti-inflammatory and antiapoptotic activities.

Topics: Administration, Oral; Animals; Anti-Infective Agents; Apoptosis; gamma-Glutamyltransferase; Glutathione; Interleukin-1beta; Interleukin-6; Intestinal Diseases; Intestine, Small; Lactoferrin; Male; Malondialdehyde; Oxidative Stress; Peroxidase; Rats; Rats, Wistar; Reperfusion Injury; Tumor Necrosis Factor-alpha

Fecal lactoferrin (FL) is a noninvasive biomarker that is elevated in Crohn disease (CD) compared to irritable bowel syndrome. The purpose of this study was to evaluate FL in identifying children with active versus inactive CD.. Fresh stool samples were collected from children with CD scheduled for endoscopy or a clinic visit, and from new outpatients who were scheduled for colonoscopy. FL was determined using a polyclonal antibody-based enzyme-linked immunosorbent assay. Physical global assessment, endoscopic findings, erythrocyte sedimentation rate (ESR), and the Pediatric CD Activity Index (PCDAI) were recorded for patients with CD. The PCDAI scores symptoms, laboratory parameters, physical examination, and extraintestinal manifestations. A score of ≤10 is inactive disease, 11 to 30 is mild active, and ≤31 is moderate to severe active.. Of 101 study patients (4- to 20-year-old, 66 boys), 31 had active CD, 23 had inactive CD, and 37 had noninflammatory bowel disease (non-IBD) conditions. Four patients with ulcerative colitis and 6 patients with polyposis were excluded from analysis. FL was significantly elevated in CD versus non-IBD (P < 0.001) and in active versus inactive CD (P < 0.001). The PCDAI and ESR were higher in active CD than in inactive CD (both P < 0.001). Using an FL cutoff of 7.25 μg/g, FL has 100% sensitivity and 100% negative predictive value in detecting active CD. Using an FL cutoff level of 60 μg/g, FL had 84% sensitivity, 74% specificity, 81% positive predictive value, and 77% negative predictive value for detecting active CD.. FL is a promising biomarker of active CD and may be more practical to use when it is not feasible to obtain all of the necessary clinical information for the PCDAI.

Topics: Adolescent; Adult; Biomarkers; Child; Crohn Disease; Enzyme-Linked Immunosorbent Assay; Feces; Female; Humans; Intestinal Diseases; Lactoferrin; Male; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Young Adult