The influence of everyday emotions on mucosal immunity: An intensive longitudinal modeling approach.

Mucosal immunity is a multifaceted system of immunological responses that provides a barrier against pathogenic invasion and can be regulated by psychosocial and neuroendocrine factors. The present study aims to elucidate the association between everyday emotional states, emotion regulation skills, and mucosal immunity by utilizing an ambulatory assessment approach. 30 healthy subjects (61% male; M = 30.18 years old) completed an emotion questionnaire (PANAS) and collected saliva samples via passive drool to determine salivary immunoglobulin-A (S-IgA) excretion rate three times a day over a period of 1 week. In a multi-level model, the influence of emotions on S-IgA, both on a within-subject and between-subject level, was estimated. We found that most of the variation in S-IgA (74%) was accounted for by within-subject changes rather than stable between-subject differences. On a within-subject level, negative emotions had a significant positive effect on S-IgA levels (b = 1.87, p = .015), while positive emotions had no effect. This effect of negative emotions was moderated by the individual emotion regulation skills, with higher regulation skills corresponding to smaller effects (b = -2.67, p = .046). Furthermore, S-IgA levels decreased over the course of a day, indicating circadian rhythmicity (b = -0.13, p = .034). These results highlight the possibilities of intensive longitudinal data to investigate the covariance between psychological and immunological states over time.

Governor Vessel Moxibustion Therapy Improves Microbiota Structure in Ankylosing Spondylitis Patients.

BACKGROUND: Clinical studies have shown that ankylosing spondylitis (AS) could be significantly improved by Governor Vessel moxibustion (GVM) therapy. OBJECTIVE: Study whether GVM therapy alleviates the clinical symptoms of AS by modulating intestinal microbiota. METHODS: A total of 9 AS patients and 9 paired healthy individuals were enrolled, and GVM therapy was provided to the AS patients. Stool, urine, and saliva samples from the healthy individuals and the AS patients before and after GVM therapy were collected, and 16S rRNA gene sequencing was performed for microbiota analysis. RESULTS: We found that GVM therapy can significantly alleviate the symptoms of AS, such as diarrhea, abdominal pain, and bloating. GVM therapy also decreased the abundances of Bacteroides and Prevotella while increasing the abundances of beneficial bacteria, such as Lactobacillus, in the gut microbiota of the AS patients. The analyses for AS clinical data and microbial abundances in AS patients revealed their multiple significant correlations (P < 0.01); for example, an unclassified crystal was positively correlated with AF12 and Delftia, monocyte had a negative correlation with Scardovia, and human leukocyte antigen-B27 was negatively correlated with Catenibacterium, Coprococcus, and Oscillospira. CONCLUSIONS: Overall, these findings demonstrate that GVM therapy can alleviate AS clinical symptoms, and at the same time, it improves the microbial structure of microbiota in AS patients. This trial is registered with Chinese Clinical Trial Registry ChiCTR2100051907.

Effectiveness of Transcutaneous Electrical Nerve Stimulation Therapy on whole Salivary Flow in Patients with Xerostomia and Healthy Adults

ABSTRACT Objective: To evaluate and compare the effectiveness of transcutaneous electrical nerve stimulation (TENS) therapy on whole salivary flow in patients with xerostomia and healthy adults. Material and Methods: Thirty subjects with a history of xerostomia and subjects withunstimulated salivary flow equal to or less than 0.5 ml in 5 min were included in the study group, and 30 healthy subjects were included in the control group. Low forced spitting unstimulated saliva was collected for five minutes in a test tube fitted with a funnel. Then electrode pads of the TENS unit were applied bilaterally on skin overlying the parotid glands and at optimal intensity, stimulated saliva was collected for 5 minutes with the same method in a separate graduated test tube. The salivary flow rate (per minute) was calculated by dividing the amount of collected saliva (volume in mL) by the duration of collection period (5 minutes) and the salivary flow rates prior and after electrostimulation were compared for both groups. The Student's t-test (unpaired and paired) was performed for group-wise comparisons. Results: In study group, the mean unstimulated salivary flow rate was 0.07 ± 0.01 mL/min. There was an 85.71% increase in salivary flow (0.13 ± 0.03 mL/min) during the TENS application and the difference was highly significant (p<0.001). In control group, the mean unstimulated salivary flow rate was 0.37 ± 0.07 mL/min. There was a 21.62% increase in salivary flow (0.45 ± 0.07 mL/min) during the TENS application and the difference was highly significant (p<0.001). An increase in mean salivary flow rate both in males and females after TENS application in both groups (p<0.001) was noted. The difference between unstimulated, stimulated and mean difference in salivary flow rate between males and females was notstatistically significant in both groups (p<0.05). Conclusion: TENS can be an effective therapy in increasing whole salivary flow rates in patients with xerostomia.

Bifidobacterium animalis subsp lactis HN019 presents antimicrobial potential against periodontopathogens and modulates the immunological response of oral mucosa in periodontitis patients.

OBJECTIVE: To evaluate the effects of Bifidobacterium animalis subsp. lactis HN019 (HN019) on clinical periodontal parameters (plaque accumulation and gingival bleeding), on immunocompetence of gingival tissues [expression of beta-defensin (BD)-3, toll-like receptor 4 (TLR4), cluster of differentiation(CD)-57 and CD-4], and on immunological properties of saliva (IgA levels) in non-surgical periodontal therapy in generalized chronic periodontitis (GCP) patients. Adhesion to buccal epithelial cells (BEC) and the antimicrobial properties of HN019 were also investigated. MATERIALS AND METHODS: Thirty patients were recruited and monitored clinically at baseline (before scaling and root planing-SRP) and after 30 and 90 days. Patients were randomly assigned to Test (SRP+Probiotic, n = 15) or Control (SRP+Placebo, n = 15) group. Probiotic lozenges were used for 30 days. Gingival tissues and saliva were immunologically analyzed. The adhesion of HN019 with or without Porphyromonas gingivalis in BEC and its antimicrobial properties were investigated in in vitro assays. Data were statistically analyzed (p<0.05). RESULTS: Test group presented lower plaque index (30 days) and lower marginal gingival bleeding (90 days) when compared with Control group. Higher BD-3, TLR4 and CD-4 expressions were observed in gingival tissues in Test group than in Control group. HN019 reduced the adhesion of P. gingivalis to BEC and showed antimicrobial potential against periodontopathogens. CONCLUSION: Immunological and antimicrobial properties of B. lactis HN019 make it a potential probiotic to be used in non-surgical periodontal therapy of patients with GCP. CLINICAL RELEVANCE: B. lactis HN019 may be a potential probiotic to improve the effects of non-surgical periodontal therapy. Name of the registry and registration number (ClinicalTrials.gov): "Effects of probiotic therapy in the treatment of periodontitis"-NCT03408548.

Immunological Outcomes of Bovine Colostrum Supplementation in Trained and Physically Active People: A Systematic Review and Meta-Analysis.

Bovine colostrum (BC) is a promising natural product applied to improve immunological functions. However, there is very little evidence on the true benefits of BC treatment on the immune function of trained and physically active people; moreover, there is no consensus on the supplementation strategy. For this reason, the aim of this meta-analysis was to quantify the effects of BC supplementation on immunological outcomes in physically active people. Data from 10 randomised controlled trials (RCTs) investigating the effect of BC supplementation in athletes and physically active adults were analysed, involving 239 participants. The results show that BC supplementation has no or a fairly low impact on improving the concentration of serum immunoglobulins (IgA, IgG), lymphocytes and neutrophils, and saliva immunoglobulin (IgA) in athletes and physically active participants. Previous research has shown BC to reduce upper respiratory tract infections; nevertheless, there is a gap of scientific knowledge on the mechanisms underlying these effects. Future RCTs are needed to focus on finding these mechanisms, as well as on preparing a clear consensus on a BC supplementation strategy in trained athletes and the physically active population.

Does Neospora caninum cause reproductive problems in pigs?

Neospora caninum is known to cause reproductive disturbances in several animal species, such as cattle, sheep, and goats. However, research on the effects of N. caninum on reproduction in pigs is limited. The objective of this study was to verify the transplacental transmission of N. caninum in pigs during several gestational stages. Twelve healthy Toxoplasma gondii and N. caninum seronegative female pigs were selected and separated into four groups of three animals each. Group A was maintained as a control group. Groups B, C, and D were inoculated intravenously with 2.9 × 107 tachyzoites of the N. caninum strain Nc1, 30 days before conception and at 45 and 90 days of gestation, respectively. Blood samples were collected from females periodically through IFAT for IgG and IgM screening to confirm the infection. At birth, after blood samples were collected from the piglets, they were then euthanized for the collection of the brain, heart, lung, liver, and diaphragm, which were then subjected to PCR. All inoculated gilts seroconverted (IgG) from the seventh day after inoculation. Nine of the 12 females expelled 24 mummified fetuses at the time of delivery, two in group A (eight), two in group B (four), three in group C (nine), and two in group D (three). Of the 24 mummified fetuses, nine were positive for N. caninum (one (25%) fetus of group B, seven (77.8%) of group C, and one (33.3%) of group D). A total of 126 live piglets were born. When the organs of the piglets from the inoculated females were analyzed by PCR for N. caninum, 88 (93.61%) were positive. All gilts inoculated produced at least one positive piglet. This demonstrates that there is transplacental transmission of N. caninum in all phases of gestation, regardless of the time of infection.

Effects of vitamin D supplementation on salivary immune responses during Marine Corps basic training.

Vitamin D's role in regulating immune responses may increase during periods of elevated psychological and physiological stress. Due to the high demands placed on US Marine Corps recruits undergoing 12 weeks of basic military training, we hypothesized that vitamin D status would be related to markers of innate mucosal immunity, and daily vitamin D supplementation would augment immune responses during training. Males (n = 75) and females (n = 74) entering recruit basic training during the summer and winter volunteered to participate in a randomized, double-blind, placebo-controlled study. Subjects received either 1000 IU vitamin D3  + 2000 mg calcium/d (n = 73) or placebo (n = 76) for 12 weeks. Saliva samples were collected pre-training, during (weeks 4 and 8), and post-training (week 12) in order to determine salivary SIgA and cathelicidin (indices of mucosal immunity) and α-amylase (indicator of stress). Initial (baseline) and post-training serum 25(OH)D levels were measured. Results were as follows: serum 25(OH)D levels were 37% higher in recruits entering training in summer compared with winter. A positive relationship was observed between baseline 25(OH)D levels and SIgA secretion rates (-SR). When stress levels were high during summer training, baseline 25(OH)D levels contributed to an increase in salivary secretory immunoglobulin A secretion rates (SIgA-SR) and cathelicidin-SR, the latter only in males. Vitamin D supplementation contributed to the changes in SIgA-SR and cathelicidin-SR, specifically SIgA-SR was higher in the treatment group. These data highlight the importance of vitamin D and mucosal immune responses during arduous basic military training when stress levels are increased.

Probiotics maintain intestinal secretory immunoglobulin A levels in healthy formula-fed infants: a randomised, double-blind, placebo-controlled study.

Formula-fed infants are more susceptible to infectious diseases because they lack the maternal immune factors transferred from breast milk, while their own immune system is still immature. As timely probiotic administration was suggested to promote immune system development in formula-fed infants, this study aimed at assessing the safety and the effects of a probiotic supplement (Bifidobacterium infantis R0033, Bifidobacterium bifidum R0071, and Lactobacillus helveticus R0052) on mucosal immune competence and digestive function in formula-fed infants. Healthy infants (3.5-6 months old) were randomised to receive either probiotic- (n=66) or placebo-supplemented (n=66) formula once a day for four weeks. In the probiotics group, faecal secretory immunoglobulin A (SIgA) levels remained similar between visit 2 (baseline; V2) and visit 3 (end-of-treatment; V3), but decreased in the placebo group. Changes in SIgA levels following treatment (log10ΔV3-V2 [95%CI]) between the probiotic and placebo groups were statistically significant (23 ng/dl [-57;102] and -137 ng/dl [-212;-62], respectively (P=0.0044; ANCOVA)). While log10ΔV3-V2 [95%CI] for salivary SIgA levels increased in both groups, this trend was more pronounced in the probiotics than in the placebo group with an increase of 123 ng/dl [9;236] and 37 ng/dL [-72;147], respectively (P=0.2829; ANCOVA). The weekly average number of stools/day was significantly higher in the probiotics group compared to placebo during the last week of treatment for the per protocol population. There was no difference in microbiota composition or anthropometric parameters between groups. No serious adverse event was reported, and all adverse events were mild and unrelated to the product or study. Our results show that formula-fed infants receiving probiotics maintained higher faecal SIgA levels at the end of the four-week treatment period, suggesting a positive effect of probiotics on SIgA production. This study demonstrates the safety of this probiotic formulation in infants. Formula-fed infants may benefit from probiotics supplementation to sustain the development of mucosal immunity.

Vitamin D3 Supplementation Reduces the Symptoms of Upper Respiratory Tract Infection during Winter Training in Vitamin D-Insufficient Taekwondo Athletes: A Randomized Controlled Trial.

Vitamin D insufficiency may be associated with increased risk of upper respiratory tract infection (URTI) in athletes. This study examined the effects of vitamin D3 supplementation on salivary immune functions and symptoms of URTI in vitamin D-insufficient taekwondo athletes. Twenty-five male taekwondo athletes, aged 19⁻22 years with vitamin D insufficiency [serum 25-hydroxyvitamin-D concentrations (25(OH)D, 31.3 ± 1.39 nmol/L)], participated in this study. They were randomized to receive 5000 IU/day of vitamin D3 (n = 13) or placebo capsule (n = 12) during 4 weeks of winter training. Blood samples were collected two times (pre- and post-tests) for analyzing serum 25(OH)D concentration while salivary samples were obtained three times (pre-, mid-, and post-tests) for secretory immunoglobulin A (SIgA) and lactoferrin analyses. The symptoms of URTI were reported daily during the intervention. Serum 25(OH)D concentration significantly increased by 255.6% in the vitamin D group, whereas in the placebo group it did not change (p < 0.001). While the significant increase in SIgA was observed in both groups (p < 0.001), elevated salivary lactoferrin level in response to winter training was found only in the placebo group (p = 0.011). The change in serum 25(OH)D concentration was negatively associated with total URTI symptoms (r = -0.435, p = 0.015). Vitamin D3 supplementation may be effective in reducing the symptoms of URTI during winter training in vitamin D-insufficient taekwondo athletes.

Effect of lactoferrin on taste and smell abnormalities induced by chemotherapy: a proteome analysis.

Cancer patients receiving chemotherapy often experience taste and smell abnormalities (TSA). To date, the underlying molecular mechanisms of this frequent side-effect have not been determined and effective treatments are not available. This study assessed the feasibility of lactoferrin (LF) supplementation as a treatment for TSA and investigate the related mechanisms through salivary proteome analysis. Nineteen cancer patients with established TSA following chemotherapy administration were enrolled in this study. Cancer patients and additional 12 healthy subjects took LF supplements, 3 tablets per day (250 mg per tablet), for 30 days. Saliva was collected at three timepoints: baseline, 30-day LF supplementation, and 30-day post-LF supplementation. Patient's TSA level, salivary proteome, and salivary minerals at each LF treatment stage were analyzed. High TSA level was associated with high concentration of salivary Fe and loss of critical salivary immune proteins. LF supplementation significantly decreased the concentration of salivary Fe (P = 0.025), increased the abundance (P < 0.05) of salivary α-amylase and Zn-α-2-GP, and led to an overall increase of expression (≥2-fold changes) of immune proteins including immunoglobulin heavy chain, annexin A1, and proteinase inhibitor. Abundance of α-amylase and SPLUNC2 were further increased (P < 0.05) at 30-day post-LF supplementation in cancer patients. At the same time, total TSA score was significantly reduced (P < 0.001) in chemotherapy patients. This study demonstrated the feasibility of developing lactoferrin supplementation as a treatment to reduce TSA caused by chemotherapy and improve cancer patient's oral immunity.

Use of low-level laser therapy on children aged 1 to 5 years with energy-protein malnutrition: A clinical trial.

BACKGROUND: Episodes of malnutrition in early childhood can produces alterations in the salivary glands. The investigation of mechanisms that can reduce the impact of malnutrition on the defenses of the organism is of the utmost important and interest to public health. The aim of this study is to evaluate the effect of low-level laser on the saliva of children aged 1 to 5 years with energy-protein malnutrition. METHODS: Mandatory inclusion criteria are diagnosis of malnutrition. The sample will consist of 50 men and women malnourished children aged 12 to 71 months. Saliva will be collected and the volume of saliva will be measured and the salivary flow rate will be determined (mL/min). Concentrations of salivary IgA in all samples will be measured using a commercial Enzyme-Linked Immunosorbent Assay (ELISA) kit. Low-level laser (laser diode) will be administered in the region of the parotid glands bilaterally as well as in the regions of the submandibular and sublingual glands. DISCUSSION: This study will be the first that investigate the effects of local laser therapy on the salivary glands of malnourished children. TRIAL REGISTRATION: Clinical.trials.gov as NCT03355313, first received in 21 November 2017.

Effect of oral functional training on immunological abilities of older people: a case control study.

BACKGROUND: Oral functional ability decreases with age, and systemic immunological ability and quality of life can also deteriorate. Continuous moderate whole-body exercise for older people is known to improve oral functional and their immunological abilities. Here, we evaluated the effect of oral exercise as an alternative training method for highly older people who cannot perform whole-body exercises. METHODS: Unstimulated whole saliva samples had been collected for three times before training as baseline data and one time after 3 and 6 weeks of training each. Participants were instructed to conduct self-massage; their tongues were used to press their orbicularis oris muscle and buccinators, and instructed to perform bilateral massage of three major glands for facilitating saliva secretion. Medical histories, daily life habits and characteristics were also collected. RESULTS: Totally 30 participants (84.2 ± 8.5 years) were enrolled. In contrast to previous researches, increase in salivary Immunoglobulin A (IgA) after the training was not observed. Interestingly, hierarchical clustering analyses revealed clear individual variations as two prominent clusters and a strong positive correlation between stimulated saliva flow rate and IgA flow rate, regardless of the continuous oral functional exercise. Only body mass index (BMI) showed significant differences between the two groups (Z = 2.06, P = 0.039, Wilcoxon rank-sum test) among all collected parameters. CONCLUSION: Oral functional training limitedly effects on salivary parameters of highly older people. On the other hand, BMI characterized salivary features more than any other parameters, such as the presence of diseases or medication use in these people. TRIAL REGISTRATION: UMIN-CTR Clinical Trial UMIN000028394 on 27/July 2017, retrospectively registered.

Children's anxiety symptoms and salivary immunoglobulin A: A mutual regulatory system?

Anxiety can impact the immune system resulting in negative health outcomes. Salivary immunoglobulin A (sIgA) is a first line of defense against foreign antigens, with lowered levels indicative of weakened mucosal immunity. Little is known about how anxiety symptoms affect the diurnal rhythm of sIgA secretion, or the longitudinal transactional sequence between the two in children and adolescents. The goals of the two studies were to: (i) explore the concurrent associations between self-reported anxiety symptoms and diurnal variations of sIgA across the day using repeated daily samples of sIgA; and (ii) examine transactional relations between children's anxiety and aggregated total amount of sIgA levels across successive periods from middle childhood (Wave 1; ages 9-12) to early adolescence (Wave 2; ages 12-15), and from early to mid- adolescence (Wave 3; ages 15-18). Concurrent results showed a steeper (positive) rise in diurnal slope of sIgA from awakening to 5 hr post-awakening in children with higher anxiety. Longitudinally, higher levels of total anxiety, and specifically, worries at Wave 1 significantly predicted lower cumulative daily levels of sIgA 3 years later at Wave 2. Lowered sIgA levels at Wave 2 in turn predicted higher anxiety at Wave 3, illustrating a "vicious cycle" feedback loop. These findings broaden our understanding of the developmental links between anxiety symptoms, the immune system, and health.

Yoga stretching for improving salivary immune function and mental stress in middle-aged and older adults.

Protection against age-related immune suppression is important in elderly individuals. This study determined the effect of yoga on mucosal immune function and mental stress. Saliva samples were collected from 23 adult women (age: 60.4 ± 10.4 years) before and after 90 minutes of yoga stretching or rest to measure secretory immunoglobulin A (SIgA), cortisol, and testosterone. The SIgA concentration and secretion rate were significantly higher after yoga than before (p < .05). The cortisol concentration and secretion rate were lower and testosterone secretion rate higher after yoga (p < .05). Yoga stretching can reduce stress and enhance mucosal immune function in elderly women.

Effects of Carbohydrate and Glutamine Supplementation on Oral Mucosa Immunity after Strenuous Exercise at High Altitude: A Double-Blind Randomized Trial.

This study analyzed the effects of carbohydrate and glutamine supplementation on salivary immunity after exercise at a simulated altitude of 4500 m. Fifteen volunteers performed exercise of 70% of VO2peak until exhaustion and were divided into three groups: hypoxia placebo, hypoxia 8% maltodextrin (200 mL/20 min), and hypoxia after six days glutamine (20 g/day) and 8% maltodextrin (200 mL/20 min). All procedures were randomized and double-blind. Saliva was collected at rest (basal), before exercise (pre-exercise), immediately after exercise (post-exercise), and two hours after exercise. Analysis of Variance (ANOVA) for repeated measures and Tukey post hoc test were performed. Statistical significance was set at p < 0.05. SaO2% reduced when comparing baseline vs. pre-exercise, post-exercise, and after recovery for all three groups. There was also a reduction of SaO2% in pre-exercise vs. post-exercise for the hypoxia group and an increase was observed in pre-exercise vs. recovery for both supplementation groups, and between post-exercise and for the three groups studied. There was an increase of salivary flow in post-exercise vs. recovery in Hypoxia + Carbohydrate group. Immunoglobulin A (IgA) decreased from baseline vs. post-exercise for Hypoxia + Glutamine group. Interleukin 10 (IL-10) increased from post-exercise vs. after recovery in Hypoxia + Carbohydrate group. Reduction of tumor necrosis factor alpha (TNF-α) was observed from baseline vs. post-exercise and after recovery for the Hypoxia + Carbohydrate group; a lower concentration was observed in pre-exercise vs. post-exercise and recovery. TNF-α had a reduction from baseline vs. post-exercise for both supplementation groups, and a lower secretion between baseline vs. recovery, and pre-exercise vs. post-exercise for Hypoxia + Carbohydrate group. Five hours of hypoxia and exercise did not change IgA. Carbohydrates, with greater efficiency than glutamine, induced anti-inflammatory responses.

Quantification of equine immunoglobulin A in serum and secretions by a fluorescent bead-based assay.

Only few quantitative reports exist about the concentrations and induction of immunoglobulin A (IgA) in mucosal secretions of horses. Despite this, it is widely assumed that IgA is the predominant immunoglobulin on mucosal surfaces in the horse. Here, two new monoclonal antibodies (mAbs) against equine IgA, clones 84-1 and 161-1, were developed and characterized in detail. Both IgA mAbs specifically bound monomeric and dimeric equine IgA in different applications, such as Western blots and fluorescent bead-based assays. Cross-reactivity with other equine immunoglobulin isotypes was not observed. The new IgA mAb 84-1 was used in combination with the previously characterized anti-equine IgA mAb BVS2 for the development and validation of a fluorescent bead-based assay to quantify total IgA in equine serum and various secretions. The IgA assay's linear detection ranged from 64pg/ml to 1000ng/ml. For the quantification of IgA in serum or in secretions an IgA standard was purified from serum or nasal wash fluid (secretory IgA), respectively. The different standards were needed for accurate IgA quantification in the respective samples taking the different signal intensities of monomeric and dimeric IgA on the florescent bead-based assay into account. IgA was quantified by the bead-based assay established here in different equine samples of healthy adult individuals. In serum the median total IgA was 0.45mg/ml for Thoroughbred horses (TB, n=10) and 1.16mg/ml in Icelandic horses (ICH, n=12). In nasopharyngeal secretions of TB (n=7) 0.13mg/ml median total IgA was measured, and 0.25mg/ml for ICH (n=12). Saliva of ICH (n=6) contained a median of 0.15mg/ml, colostrum of Warmbloods (n=8) a median of 1.89mg/ml IgA. Compared to IgG1 and IgG4/7 quantified in the same samples, IgA appeared as the major immunoglobulin isotype in nasopharyngeal secretions and saliva while it is a minor isotype in serum and colostrum. The newly developed monoclonal antibodies against equine IgA and the resulting bead-based assay for quantification of total IgA can notably improve the evaluation of mucosal immunity in horses.

Oropharyngeal Colostrum Administration in Very Low Birth Weight Infants: A Randomized Controlled Trial.

OBJECTIVES: Studies have confirmed the safety of oropharyngeal administration of colostrum in very low birth weight infants. However, the effect of oropharyngeal administration of colostrum on immune system is inconclusive. This study aims to evaluate the effect of oropharyngeal administration of colostrum on secretory immunoglobulin A and lactoferrin in very low birth weight infants. DESIGN: Randomized controlled trial. SETTING: Forty-bedded neonatal ICU in a university children's hospital in the People's Republic of China. PATIENTS: Very low birth weight infants were allocated to the study group (n = 32) and control group (n = 32). INTERVENTION: The intervention was oropharyngeal administration of 0.2 mL of their mother's colostrum every 4 hours for 7 days. The control group received saline solution. MEASUREMENTS AND MAIN RESULTS: Secretory immunoglobulin A and lactoferrin in urine and saliva were measured within 24 hours of life (baseline) and at 7 and 21 days. Primary outcomes were changes of secretory immunoglobulin A and lactoferrin in urine and saliva between baseline and at 7 and 21 days. Infant's clinical data were also collected during hospitalization. Change from baseline in lactoferrin in saliva at 7 days (5.18 ± 7.07 vs -1.74 ± 4.67 µg/mL; p < 0.001) and 21 days (5.31 ± 9.74 vs -1.17 ± 10.38 µg/mL; p = 0.02) shows statistic difference. No differences were found of lactoferrin in urine and also no differences of secretory immunoglobulin A in urine and saliva. There were also no differences between days to full enteral feeding, occurrence rate of clinical sepsis, proven sepsis, and necrotizing enterocolitis. CONCLUSIONS: Oropharyngeal administration of colostrum can increases the level of lactoferrin in saliva in very low birth weight infants. No effect could be documented of secretory immunoglobulin A and lactoferrin in urine. Larger trials are needed to better describe the benefit of oropharyngeal administration of colostrum, if any, in very low birth weight infants.

Comparisons of IgA response in saliva and colostrum against oral streptococci species.

The present study compared IgA specificity against oral streptococci in colostrum and saliva samples. Sixty-two mother-and-child pairs were included; samples of colostrum (C) and saliva (MS) were collected from the mothers and saliva samples were collected from babies (BS). The specificity of IgA against Streptococcus mutans and S. mitis were analyzed by western blot. Only 30% of babies' samples presented IgA reactivity to S. mutans, while 74 and 80% of MS and C, respectively, presented this response. IgA reactivity to S. mutans virulence antigens (Ag I/II, Gtf and GbpB) in positive samples showed differences between samples for Gtf and especially for GbpB (p < 0.05), but responses to Ag I/II were similar (p > 0.05). The positive response of Gtf-reactive IgA was different between C (90%) and MS (58%) samples (p < 0.05), but did not differ from BS (p > 0.05). GbpB was the least detected, with 48 and 26% of C and MS, and only 5% of BS samples presenting reactivity (p > 0.05). Eight percent of MS and C samples presented identical bands to SM in the same time-point. In conclusion, the differences of IgA response found between C and MS can be due to the different ways of stimulation, proliferation and transportation of IgA in those secretions. The colostrum has high levels of IgA against S. mutans virulence antigens, which could affect the installation and accumulation process of S. mutans, mainly by supplying anti-GbpB IgA to the neonate.

Oral colostrum priming shortens hospitalization without changing the immunomicrobial milieu.

OBJECTIVE: Oral colostrum priming (OCP) after birth in preterm infants is associated with improved weight gain and modification of the oral immunomicrobial environment. We hypothesized that OCP would modify salivary immune peptides and the oral microbiota in preterm infants. STUDY DESIGN: We conducted a prospective, randomized clinical trial to determine the effects of OCP on salivary immune peptide representation in preterm infants (<32 weeks completed gestation at birth). Saliva samples were collected before and after OCP. Salivary immune peptide representation was determined via mass spectroscopy. Oral microbiota representation was determined via sequencing of the 16S rRNA gene. RESULTS: Neonates who received OCP (n=48) had a 16-day reduction in the median length of hospitalization as compared with infants who did not receive OCP (n=51). No differences in salivary immune peptide sequence representation before OCP between groups were found. Longitudinal changes in peptides were detected (lysozyme C, immunoglobulin A, lactoferrin) but were limited to a single peptide difference (α-defensin 1) between primed and unprimed infants after OCP. We found no difference in microbial diversity between treatment groups at any time point, but diversity decreased significantly over time in both groups. OCP treatment marginally modified oral taxa with a decline in abundance of Streptococci in the OCP group at 30 days of life. CONCLUSIONS: OCP had neither an effect on the salivary peptides we examined nor on overall oral bacterial diversity and composition. Infants who received OCP had a reduced length of hospitalization and warrants further investigation.