Transcriptional frameshifts contribute to protein allergenicity

This research published in the Journal of Clinical Investigation, reveals the patented mechanism of the Infidelity transcription, according to which, errors in the copy of DNA and RNA generate positively charged proteins, allowing the induction of the allergic antibody IgE, for both humans and animals. The discovery of a common cause for allergens paves the way for the prevention and treatment of allergies.

Publication

* This publication is produced by a research group that includes the biotechnology company Genclis (Genomic Clinical Synergy).

*H&H group is collaborating with Genclis in other innovation projects.

 


How does the brain develop?

The brain is one of the body's most complex organs and is at the centre of our nervous system. Exploring how the brain functions is necessary to be able to understand overall human health, which is why brain development is one of BINC key areas of expertise.

Check out this infographic to understand the basics of how the brain functions.

Brain development infographics

 


Webinar "DHA and ARA infant feeding: How they came to be regarded as conditionally essential?"

Join our webinar "DHA and ARA infant feeding: How they came to be regarded as conditionally essential?"
In this webinar Professor Tom Brenna, will explain long-chain PUFA docosahexaenoic acid (DHA) and arachidonic acid (ARA) roles in infant nutrition, showcasing the major studies outcomes in this topic.

 

Watch the webinar


BINC at FASEB international Research Conference

BINC sponsored the FASEB international Science Research Conference held in West Palm Beach Florida from 21 to 26 July in presence of the leading scientific experts in the human milk research.

Key science players representing academic, clinical, industrial, and government organizations shared the latest research and scientific outputs around “The Origins and Benefits of Biologically Active Components in Human Milk”.

This sponsorship strengthens BINC and H&H research presence towards the Human milk science research globally.


World of Microbiome Conference:  Understanding the secret of the microbiome

BINC was proud to be a sponsor at the World of Microbiome: Pregnancy & Infancy Conference (WoMPBI 2019) in Milan, from 31 October to 2 November. This congress brought together world-class science to 400 participants, mostly KOLs and healthcare professionals, experts in microbiology immunology, neonatology and pediatrics. In this event, BINC team highlighted our scientific activities and research programmes.

 


DOHaD Melbourne 2019: Investing in a Healthy Future for All

BINC was one of the sponsors of DOHaD (Development Origin of Health and Disease) conference held from 20 to 23rd October 2019, in Melbourne. BINC areas of expertise and research grants towards infant health were introduced to Congress during which   1000 clinical researchers and healthcare professionals addressed the many challenges that currently impact the health of mothers and infants.


Webinar now on- demand"Could breast milk set the child on a path with no allergy?

"Could breast milk set the child on a path with no allergy? Insight from translational research": a webinar by Professor Valerie Verhasselt. 

Discover the most recent evidence on the influence of breast milk on long term immune health.
Prebiotics, probiotics, varied antimicrobials molecules, have all the potential to shape the composition and function of the establishing gut microbiota, which is known to be a major determinant in susceptibility to non-communicable disease such as allergy.
Understanding how maternal breast milk composition programs infant immune system should provide clues to ensure allergy prevention in every breastfed child.

WATCH THE WEBINAR


H&H Global Research abstracts

We would like to present the four H&H Global Research team abstracts that should have been presented in the scope of the 6th World Congress of Pediatric Gastroenterology, Hepatology and Nutrition in Copenhagen, from 3 to 6 June 2020.

Great work from the H&H Global Research team in Moorepark and Guangzhou.


Topical Area: Nutrition/infant feeding

Xiang Cohort Study: An association of breast milk composition with maternal BMI and infant growth during the first three months of life.

Objectives: The aim of this study was to establish a mother and child cohort in the Chinese population and to investigate human milk (HM) composition and its relationship with infant growth and development during the first three months of life.

Methods: 110 Chinese mother and infant pairs were included in this prospective cohort. Changes of total energy, total fat, total protein, true protein, carbohydrate and osteopontin (OPN) in milk of Chinese mothers at one (T1), two (T2), three (T3) months lactation were analyzed. HM fatty acid (FA) profiles were measured by GC and HM proteomic profiling was conducted by matrix-assisted laser desorption ionization (MALDI), time-of-flight (TOF) mass spectrometry (MS). BMI of the mothers and infant growth indicators, such as weight, length, BMI and head circumference were also recorded at three time points.

Results: Total energy, total fat, total protein, true protein and OPN levels significantly decreased during the first three month of lactation (P < 0.05). Similarly, medium and long-chain saturated FA, including C13:0, C16:0, C20:0, C22:0 and C24:0, and n-6 polyunsaturated (PU) FA including C20:3n6 and C20:4n6, and n-3 PUFA, including C18:3n3, C20:3n3 and n6/n3 ration all significantly decreased over time (P < 0.05). Conversely, short-chain fatty acids, such as butyrate and C6:0, increased during the first three months (P <0.05). HM proteomic analyses distinguished protein composition over time (P = 0.001). Personalized analyses demonstrated that the HM of high-BMI (BMI>25) mothers presented increased total fat, total protein and total energy at T1 and/or T3, and increased OPN at T3 when compared with the normal-BMI (18<BMI<20) mothers (p < 0.05). Similarly, the content of n6 PUFA including C18:3n6 at T1, C20:3n6 at T1-T3 and n6/n3 ratio at T3 were significantly higher in high-BMI mother’s milk. However, the content of MUFA, mainly C18:1 was significantly higher in low-BMI mother’s milk. In addition, BMI of the mothers was positively correlated with the specific FA C20:3n6 (P <0.05,r = 0.27, 0.34, 0.36 respectively) as well as the head circumference (HC)  of infants (P <0.05,r = 0.31, 0.33, 0.20 respectively) over the three time points.

Conclusion: This study showed that HM changes over time and many of the studied components decreased in concentration during the first three months of lactation. It also concluded that maternal postpartum BMI can influence the FA profile of HM and HC of the infants. This study provides more evidence to the Chinese breast-milk database and further knowledge of HM FA function to support future strategies for the health growth and development of Chinese infants.

Author (s)

Feitong Liu, Xuyi Peng, Jie Li, Juchun Chen, Shuyuan Yan, Jonathan Lane, Patrice Malard

Institute(s)

H&H Group Global Research and Technology Center, Guangzhou, China; School of Food Science, South China Agriculture University; Division of Laboratory Medicine, Zhujiang Hospital, Southern Medical University; Child Health Care Center, Changsha Hospital for Maternal and Child Care, Changsha, China


Topical Area: Nutrition/The gut microbiome

Interrogation of Human Milk Oligosaccharide Utilization Pathways in an Infant Bifidobacterial Community by integrated Genomics and Proteomics

Objectives and Study: Bifidobacteria are associated with positive effects on human health. The influence of human milk oligosaccharides (HMO) on the growth of bifidobacteria is of increasing interest; however, the mechanisms involved in carbohydrate metabolism in a bifidobacterial community are not clearly understood. The aim of this study was to characterize essential gene and protein data sets involved in carbohydrate utilization in a community of four commercial infant Bifidobacterium strains.

Methods: PacBio SMRT sequencing was used to determine the whole genome sequences of all commercial probiotic strains including Bifidobacterium longum subsp. infantis (x2), Bifidobacterium bifidum and Bifidobacterium breve. A subsystem-based comparative genomics approach was used to reconstruct carbohydrate utilization pathways and identify enzymes, transporters and transcriptional regulators related to assimilation of HMO. In order to validate the HMO degradation pathways identified, Bifidobacterium strains were grown in combination in the presence of HMO isolated from human milk. Proteins expressed during growth on HMO were quantified using label-free proteomic analysis via a Q-Exactive mass spectrometer.

Results: Whole genome sequencing of the four Bifidobacterium strains revealed diverse genomic architecture enriched in carbohydrate metabolism genes, which was distinct between species, with some notable differences even amongst the B. infantis strains. One of the B. infantis strains contained the largest proportion of carbohydrate metabolism features (16.4%), while the B. bifidum strain had the lowest proportion of features dedicated to carbohydrate metabolism (11.3%). All strains contained genes encoding for enzymes involved in the GNB/LNB pathway. The B. breve strain, unlike the other strains, lacked genes encoding glycosyl hydrolases (GHs) necessary for hydrolysis of complex HMO structures. Proteome changes during exposure of these strains to HMO were quantified and 235 proteins were detected at higher abundance versus a lactose control. The largest proportions of differentially abundant proteins were involved in carbohydrate metabolic pathways (20%) or transport/localization processes (13%). In B. bifidum, GH proteins involved in assimilation of HMO were found in higher abundances including fucosidases, sialidase, β-galactosidase, and β-N-acetylhexosaminidase. Increased expression of proteins involved in the B. infantis 'HMO Island' was also observed, including higher abundances of solute-binding proteins, transporters, a fucosidase, and a β-galactosidase. A >10 fold increase in abundance of lacto-N-phosphorylase in B. breve was observed during growth on HMO, signifying preferential consumption of HMO-derivatives released by other strains within the community.

Conclusion: The combined genomic-proteomic approaches described in this study allows for an in-depth understanding of carbohydrate resource sharing relationships that exist between dominant members of the infant gut microbiota. This study provides new insights on diverse carbohydrate utilization networks in Bifidobacteria that can be employed in metabolic modelling, phenotype prediction and the targeted development of novel symbiotic formulations.

Author(s)

Clodagh Walsh, Rebecca A. Owens, Jonathan A. Lane, Francesca Bottacini, Wiley Barton, Paul D. Cotter, Douwe van Sinderen, Rita M. Hickey

Institute(s)

Teagasc Food Research Centre, Moorepark, Food Bioscience, Cork, Ireland, National University of Ireland, Maynooth, Human Health Institute, Co. Kildare, Ireland, Health and Happiness Group, Global Research and Technology Center, Cork, Ireland, APC Microbiome Institute, University College Cork, School of Microbiology, Cork, Ireland


Topical Area: Nutrition/The gut microbiome

Community driven metabolism of Human Milk Oligosaccharides by a consortia of Bifidobacteria spp.

Objectives and Study: Bifidobacteria are associated with a host of health benefits and are the most widely used probiotics in humans. These bacteria are highly abundant in the intestinal microbiota of healthy breastfed infants. Infant-associated Bifidobacteria spp. include Bifidobacterium longum subsp. infantis, Bifidobacterium bifidum and Bifidobacterium breve. A key adaptation, facilitating the establishment and dominance of these species in the breastfed infant gut microbiota, is an ability to consume and metabolise specific sugars only found in breastmilk which are indigestible by the infant, known as Human Milk Oligosaccharides (HMO). In this study, we aimed to characterise the metabolic capability and co-operative metabolism of a community of four commercial infant Bifidobacterium strains when grown on HMO.

Methods: Phenotypic profiling was performed on the four-strain combination (Bifidobacterium longum subsp. infantis x 2, Bifidobacterium bifidum and Bifidobacterium breve) when culture on HMO to understand the physiology and mechanisms underlying HMO utilization in a community environment. Metabolism was measured using growth curves, HMO-High Performance Liquid Chromatography (HPLC) depletion and organic acid analysis (combination of Gas Chromatography Mass Spectrometry and HPLC). Each analysis was performed using three different HMO substrates (2'-fucosyllactose alone and oligosaccharides isolated from human milk representing non-secretor and secretor status). Media with no carbohydrate source was used as a control.

Results: The four-strain combination resulted in total Bifidobacterium numbers increasing (>16%, p≤0.05) in comparison to single strain cultivation. Over a 24 hour period, the relative abundance of B. breve increased by >50% during co-cultivation with the other strains despite demonstrating limited ability to consume HMO in pure culture. Growth of the strains on secretor HMO resulted in an increase in growth of 14% and 64% when compared to non-secretor HMO and 2'-FL, respectively. HPLC analysis revealed that an increasing number of HMO were consumed by the bacteria over time. Metabolomics confirmed the production of formate, acetate, 1,2-propanediol and lactate. An overall increase in health-promoting organic acids was noted during co-cultivation of all four strains, thus, demonstrating that syntrophic relationships between bifidobacterial strains, increases flux along central metabolic pathways.

Conclusion: This data highlights the cooperative nature of bifidobacterial strains which may reflect their behaviour within an infant ecosystem and how sharing HMO resources maximises nutrient consumption from the diet. The synergistic effect of multiple HMO structures and multiple Bifidobacterium strains results in higher cell numbers and a healthier balance of metabolites, which may have potential health implications for the host. We propose that this social behaviour adds to the diversity and dominance of Bifidobacterium in early life and highlights opportunities for development of new diet and microbiota based therapies to promote infant health.

Author(s)

Clodagh Walsh, Jonathan A. Lane, Helen Slattery, Douwe van Sinderen, Rita M. Hickey

Institute(s)

Teagasc Food Research Centre, Moorepark, Food Bioscience, Cork, Ireland, H&H Group, Global Research and Technology Center, Cork, Ireland, APC Microbiome Institute, University College Cork, School of Microbiology, Cork, Ireland


Topical Area: Nutrition/Neonatal and preterm nutrition

A combination of 2´-Fucosyllactose and Osteopontin attenuates 2,4-dinitrochlorobenzene (DNCB)-induced contact dermatitis murine model

Objectives and Study: Atopic dermatitis (AD) is a common chronic inflammatory skin disease that is often associated with skin barrier dysfunction leading to a higher frequency of bacterial and viral skin infections. The protective effect of breastfeeding against the development of AD and other allergic diseases is well accepted but not fully understood. In this study, the impact of osteopontin (OPN), a multi-functional glycoprotein found in mothers' milk, and 2´-fucosyllactose (2'-FL), the predominant human milk oligosaccharide, alone or in combination, was determined on AD-like symptoms.

Methods: Repeated epicutaneous application of 2,4-dinitrochlorobenzene (DNCB) was performed on the ear and dorsal skin of BALB/c mice to induce AD-like symptoms and skin lesions. Oral administrations of OPN and/or 2'-FL at concentrations commonly associated with mature mothers milk were performed and AD-like symptoms, behavior, water loss, immune cell activation, immunoglobulin and cytokine expression was recorded.

Results: OPN and/or 2'-FL decreased serum IgE levels and limited the infiltration of eosinophils and mast cells to the dermal tissues in the DNCB-induced AD mice. Furthermore, OPN and 2'-FL reduced Th2 and Th17 responses, leading to an attenuated cutaneous inflammatory response. Interesting, combinations of OPN and 2-FL had a more pronounced effect on IgE expression, eosinophil and Th cell response when compared to the use of OPN or 2-FL alone.

Conclusion: It could be concluded that OPN and 2'-FL synergistically attenuate DNCB-induced AD-like skin lesion in a murine model through modulating T cell-elicited immune responses and CD4+ T cell polarization.

Author(s)

Xi Chen, Jiaqi Zeng, Jonathan A. Lane, Rush Deng, Patrice Malard, Daming Zuo

Institute(s)

Southern Medical University, Department of Immunology School of Basic Medical Sciences, Guangzhou, China, 2H&H Group, Global Research and Technology Center, Cork, Ireland, H&H Group, Global Research and Technology Center, Guangzhou, China

 


Apply to our Grants programme 2020

Biostime Institute for Nutrition and Care (BINC) in Geneva stimulates innovation and pre-competitive academic research towards maternal and infant health, with emphasis on nutrition, care, and psychology. Every year, BINC research grants provide financial support for innovative research projects from scientists based in high-ranking universities, hospitals or leading academic institutions. The grants are up to 50,000 euros per project for pre-clinical research and up to 100,000 euros per project for clinical research. Applications for 2020 are now open and due 16 March -

apply here


Child obesity and early nutrition

Obesity is an excessive body fat accumulation that presents a risk to health. For children under 5 years old, overweight and obesity are defined as being 2 or 3 standard deviations above the median of the WHO growth standards. The incidence of overweight children under 5 years increased from 31 million in 1990 to 41 million in 2016.

The repercussions on health and quality of life are immediate and can have an impact along the whole lifespan. Children affected by obesity have lower educational attainment and more psychosocial problems like poor self-esteem, anxiety and depression. In addition, the likelihood of being obese as an adult is increased, as it is the risk of non-communicable diseases like type 2 diabetes, cardiovascular diseases, some types of cancer and musculoskeletal disorders.

Consumption of sweetened beverages, energy-dense diets and inadequate physical activity are determinant in the development of childhood obesity, but complex interactions between the child, the family and the community play also a central role. Young children depend on the food that is made available to them by their caregivers, and they mimic parental behaviours from very young age. In turn, family’s diet and physical activity are influenced by their community; for example, by the availability of healthy food vendors and sport facilities. Because of this, successful interventions to prevent childhood obesity must involve parents, schools and community.

Opportunities for obesity prevention by early life interventions

Early life factors can shape the risk of obesity and other non-communicable diseases. The developmental origins of health and disease hypothesis (DOHaD) postulates that experiences during critical periods of development have consequences on short and long-term health.

Pregnancy

Epidemiological studies have established an ‘U’ shape relationship of obesity risk and birth weight, which is a proxy of nutrition during the intrauterine period. Low birth weight can be the result of maternal undernutrition, placental insufficiency, or other factors that limit the nutrients available to the developing foetus. On the other hand, maternal obesity, excessive weight gain during pregnancy or gestational diabetes can result in excessive nutrient transfer and high birth weight.

Lactation

Besides its numerous benefits for infant and maternal health, breastfeeding has also been associated to decreased risk of obesity. Human milk composition adapts to the specific needs of the growing infant and contains bioactives that contribute to organ maturation and microbial colonization. In addition, breastfeeding may support the self-regulation of food intake.

Complementary feeding period

During the complementary feeding period, children have their first experiences with different foods and textures. Research has shown that food habits established during infancy can track into childhood and adolescence. Repeated exposure to a variety of nutritious foods including fruits and vegetables will maximize the likelihood of consuming them as part of a healthy diet later in life.

Interventions during early life have the potential to prevent childhood obesity. Efforts should be focused on optimizing nutrition and weight gain during pregnancy, early detection and management of gestational diabetes and promotion of breastfeeding. In addition, support must be given to parents to introduce a wide variety of healthy foods and promote regular physical activity.