Probiotics to prevent Staphylococcus aureus disease?
Gut microbes. 2020;(1):94-101
There are a plethora of probiotic formulae that supposedly benefit human health on the market. However, the scientific underpinnings of the claimed benefits have remained poorly established. Scientific evidence is now increasingly being provided that explains those benefits, for example, by immune-stimulatory effects or inter-bacterial competition between beneficial and pathogenic bacteria. In our recent study (Piewngam et al. Nature 2018), we show that Bacillus colonization of the human intestine is negatively correlated with that of the human pathogen, Staphylococcus aureus. This type of colonization resistance is achieved by secretion of a class of lipopeptides by Bacillus species that inhibits S. aureus quorum-sensing signaling, which we found is crucial for S. aureus intestinal colonization. Here, we discuss what these findings imply for the general role of S. aureus intestinal colonization, the role of quorum-sensing in that process, and potential alternative ways to control S. aureus infection.
Factors Influencing Growth of Children Aged 12-24 Months in the Tanga Region, Tanzania.
Journal of tropical pediatrics. 2020;(2):210-217
BACKGROUND The first 1000 days of life, from conception to the second birthday, offer a unique window of opportunity for optimal growth, critical for future health. The primary aim of this study was to analyze growth of children between 12 and 24 months age in Tanzanian children, and to explore possible predictors for growth. METHODS Observational, cross-sectional study performed between March and April 2017. Eligible children, and their mothers, attended routine follow-up at two health clinics in Tanga, Tanzania. At the study day, the child's weight and height were recorded. The mothers answered a structured interview regarding breastfeeding, immunization and socioeconomic conditions. RESULTS We recruited 300 mother-child pairs. Median [interquartile range (IQR)] age at study visit was 16 (14-20) months. Mothers reported that 170 (57%) of their children were exclusively breastfed for a minimum of 6 months; median (IQR) 6 (4-6) months. Using the World Health Organization (WHO) standard growth curves, mean weight-for-age Z-score was -0.30 and mean length-for-age Z-score was -0.47. Children whose mothers had higher education had higher Z-scores for weight and length compared to children of mothers with lower education. Education remained the most important predictor for growth also after adjusting for other variables. Overall, 48/300 (16%) were moderate-severe stunted and 25/300 (8.4%) had moderate-severe underweight. CONCLUSION Children aged 12-24 months in this region of Tanzania had weight and height below the WHO standard. Higher educated mothers had children with better growth parameters. Duration of exclusive breastfeeding was long, but did not predict growth parameters.
Volume-Based Feeding Enhances Enteral Delivery by Maximizing the Optimal Rate of Enteral Feeding (FEED MORE).
JPEN. Journal of parenteral and enteral nutrition. 2020;(6):1038-1046
BACKGROUND The importance of enteral nutrition (EN) in critically ill patients is well documented. However, actual administration of EN frequently does not amount to prescribed nutrition goals. Persistent underfeeding may lead to impaired immune response, increased mortality, and higher costs. Traditionally, EN uses a rate-based approach, utilizing slow titration to goal and a final fixed hourly rate, regardless of interruptions in feeding. Volume-based feeding (VBF) establishes a 24-hour EN goal volume, and the rate varies to achieve this daily goal when interruptions occur. MATERIALS AND METHODS This was a retrospective, single-center, quasi-experimental study comparing traditional rate-based feeding (RBF) to VBF in adult patients admitted to the medical and neurosurgical intensive care units (ICUs). The primary outcome was mean percentage of total goal energy received after EN initiation until 7 days, transfer from ICU, removal of feeding tube, or oral diet order placed. Secondary outcomes included mean percentage of total goal protein received, percentage of patients meeting 80% of nutrition goals, incidence of gastric residual volumes >400 mL, and incidence of moderate hyperglycemia (>250 mg/dL). RESULTS The study enrolled 189 patients. Mean percentage of goal energy delivered (75% RBF, 102% VBF; P < .001) and goal protein delivered (68% RBF, 87% VBF; P < .001) was significantly higher with VBF compared with RBF. CONCLUSION VBF demonstrated a significant increase in energy and protein delivery with no major safety or tolerability issues. VBF should be considered for use in ICU patients to optimize nutrition delivery.
Associations between maternal inflammation during pregnancy and infant birth outcomes in the Seychelles Child Development Study.
Journal of reproductive immunology. 2020;:102623
PROBLEM Markers of maternal inflammation may determine infant birth outcomes. METHOD OF STUDY Maternal serum samples were collected at 28 weeks gestation (n = 1418) in the Seychelles Child Development Study Nutrition Cohort 2 and analyzed for immune markers by MSD multiplex assay, including cytokines from the Th1 (IFN-γ, IL-1β, IL-2 and TNF-α) and Th2 (IL-4, IL-5, IL-10) subsets, with IL-6, MCP-1, TARC, sFlt-1 and VEGF-D. Associations of log-transformed immune markers with birthweight, length, head circumference and gestational age were assessed by multiple linear regression models, which were adjusted for maternal age, BMI, parity, child sex, gestational age and socioeconomic status. RESULTS Neither total Th1, Th2 nor Th1:Th2 were significantly associated with any birth outcome. However, the angiogenesis marker VEGF-D was predictive of a lower birthweight, (β = -0.058, P = 0.017) and birth length (β = -0.088, P = 0.001) after adjusting for covariates. Higher concentrations of CRP were predictive of a lower birthweight (β = -0.057, P = 0.023) and IL-2 (β = 0.073, P = 0.009) and the chemokine MCP-1 (β = 0.067, P = 0.016) were predictive of a longer gestational age. CONCLUSIONS In our cohort of healthy pregnant women, we found no evidence for associations between the Th1 or Th2 inflammatory markers with birth outcomes. However, VEGF-D and CRP appear to predict lower birthweight and IL-2 and MCP-1 a longer gestation. Greater understanding is required of the variation in these immune markers at different gestational stages, as well as the factors which may regulate their balance in healthy pregnancy. n = 233.
Rapid Generation of Sustainable HER2-specific T-cell Immunity in Patients with HER2 Breast Cancer using a Degenerate HLA Class II Epitope Vaccine.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2020;(5):1045-1053
PURPOSE Patients with HER2+ breast cancer benefit from trastuzumab-containing regimens with improved survival. Adaptive immunity, including cytotoxic T-cell and antibody immunity, is critical to clinical efficacy of trastuzumab. Because Th cells are central to the activation of these antitumor effectors, we reason that HER2 patients treated with trastuzumab may benefit by administering vaccines that are designed to stimulate Th-cell immunity. PATIENTS AND METHODS We developed a degenerate HER2 epitope-based vaccine consisting of four HLA class II-restricted epitopes mixed with GM-CSF that should immunize most (≥84%) patients. The vaccine was tested in a phase I trial. Eligible women had resectable HER2+ breast cancer and had completed standard treatment prior to enrollment and were disease free. Patients were vaccinated monthly for six doses and monitored for safety and immunogenicity. RESULTS Twenty-two subjects were enrolled and 20 completed all six vaccines. The vaccine was well tolerated. All patients were alive at analysis with a median follow-up of 2.3 years and only two experienced disease recurrence. The percent of patients that responded with augmented T-cell immunity was high for each peptide ranging from 68% to 88%, which led to 90% of the patients generating T cells that recognized naturally processed HER2 antigen. The vaccine also augmented HER2-specific antibody. Immunity was sustained in patients with little sign of diminishing at 2 years following the vaccination. CONCLUSIONS Degenerate HLA-DR-based HER2 vaccines induce sustainable HER2-specific T cells and antibodies. Future studies, could evaluate whether vaccination during adjuvant treatment with trastuzumab-containing regimens improves patient outcomes.
Molecular Modeling of the Interaction Between Stem Cell Peptide and Immune Receptor in Plants.
Methods in molecular biology (Clifton, N.J.). 2020;:67-77
Molecular docking enables comprehensive exploration of interactions between chemical moieties and proteins. Modeling and docking approaches are useful to determine the three-dimensional (3D) structure of experimentally uncrystallized proteins and subsequently their interactions with various inhibitors and activators or peptides. Here, we describe a protocol for carrying out molecular modeling and docking of stem cell peptide CLV3p on plant innate immune receptor FLS2.
Gut microbiota as an "invisible organ" that modulates the function of drugs.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2020;:109653
Gut microbiota plays an important role in the gut and have become a hotspot of recent research interests. Commensal microbiota in gut exert a variety of effects on the host, from shaping the structure and function of the gut and the immune system to the modulation of nutrient status of the host and the treatment outcomes of some drugs. Gut microbiota and its enzyme product and subsequent products, such as short-chain fatty acid and bile acid, play important roles in the biotransformation of drugs via directly or indirectly affecting drug absorption, toxicity, metabolism and bioavailability. Drugs, especially antibiotics, also affect the homeostasis of probiotics and the integrity and function of the intestinal mucosa. These interplaying processes produce a variety of important metabolites of the host and drugs and affect the balance of microbiota and the mucosal barrier then modulate the function of drugs. Gut microbiota imbalance is associated with a broad range of disease mechanisms, and this association denotes a new drug-therapeutic avenue. The present review summarizes how gut microbiota acts as an "invisible organ" to directly or indirectly modulate the function of drugs, on the aspects of probiotic homeostasis, drugs and host nutritional metabolism, AJC, mucus layer and microfold cells.
[Clinical effect of recombinant human interferon α1b adjuvant therapy in infectious mononucleosis: a prospective randomized controlled trial].
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics. 2020;(9):953-957
OBJECTIVE To study the clinical effect of recombinant human interferon α1b assisting acyclovir on immune function, inflammatory factors, and myocardial zymogram in children with infectious mononucleosis (IM). METHODS A total of 182 children with IM who were admitted to the hospital from January to December, 2018, were divided into an observation group with 91 children and a control group with 91 children using a random number table. The children in the control group were treated with intravenous drip of acyclovir, and those in the observation group were treated with inhalation of recombinant human interferon α1b in addition to the treatment in the control group. The two groups were compared in terms of clinical symptoms, immune function, inflammatory response, myocardial zymogram, and adverse reactions. RESULTS Compared with the control group, the observation group had significantly shorter time to body temperature recovery and disappearance of isthmopyra, cervical lymph node enlargement, hepatomegaly, and splenomegaly (P<0.05). After treatment, both groups had significant increases in CD4+, CD4+/CD8+, and CD19+, and the observation group had significantly higher levels of these markers than the control group (P<0.05). After treatment, both groups had significant reductions in the levels of CD8+, tumor necrosis factor-α, interlukin-6, creatine kinase, and creatine kinase-MB, and the treatment group had significantly lower levels of these markers than the control group (P<0.05). There was no significant difference in the incidence rate of adverse reactions between the two groups after treatment (P>0.05). CONCLUSIONS For children with IM, recombinant human interferon α1b assisting acyclovir can effectively improve immune function, inhibit inflammatory reaction, reduce myocardial injury, and thus alleviate clinical symptoms.
The conundrum of human immune system "senescence".
Mechanisms of ageing and development. 2020;:111357
There is a great deal of debate on the question of whether or not we know what ageing is (Ref. Cohen et al., 2020). Here, we consider what we believe to be the especially confused and confusing case of the ageing of the human immune system, commonly referred to as "immunosenescence". But what exactly is meant by this term? It has been used loosely in the literature, resulting in a certain degree of confusion as to its definition and implications. Here, we argue that only those differences in immune parameters between younger and older adults that are associated in some definitive manner with detrimental health outcomes and/or impaired survival prospects should be classed as indicators of immunosenescence in the strictest sense of the word, and that in humans we know remarkably little about their identity. Such biomarkers of immunosenescence may nonetheless indicate beneficial effects in other contexts, consistent with the notion of antagonistic pleiotropy. Identifying what could be true immunosenescence in this respect requires examining: (1) what appears to correlate with age, though generality across human populations is not yet confirmed; (2) what clearly is part of a suite of canonical changes in the immune system that happen with age; (3) which subset of those changes accelerates rather than slows aging; and (4) all changes, potentially population-specific, that accelerate agig. This remains an immense challenge. These questions acquire an added urgency in the current SARS-CoV-2 pandemic, given the clearly greater susceptibility of older adults to COVID-19.
Cu Homeostasis in Bacteria: The Ins and Outs.
Copper (Cu) is an essential trace element for all living organisms and used as cofactor in key enzymes of important biological processes, such as aerobic respiration or superoxide dismutation. However, due to its toxicity, cells have developed elaborate mechanisms for Cu homeostasis, which balance Cu supply for cuproprotein biogenesis with the need to remove excess Cu. This review summarizes our current knowledge on bacterial Cu homeostasis with a focus on Gram-negative bacteria and describes the multiple strategies that bacteria use for uptake, storage and export of Cu. We furthermore describe general mechanistic principles that aid the bacterial response to toxic Cu concentrations and illustrate dedicated Cu relay systems that facilitate Cu delivery for cuproenzyme biogenesis. Progress in understanding how bacteria avoid Cu poisoning while maintaining a certain Cu quota for cell proliferation is of particular importance for microbial pathogens because Cu is utilized by the host immune system for attenuating pathogen survival in host cells.