Research project
36 | monthsGLUTTON

Tackling milk formula composition to improve infant nutrition

Related toSpoke 06

Principal investigators
Antonio Dario Troise,Laura Cavallarin

Other partecipantsLoredana Terran
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Highlights

Project partners

Other partners

ISPA, ISPAAM, IBBA

Task involved

Task 6.1.1.

Profiling of vulnerable targets (in connection with SPOKE 5) through: a) analyses of existing data in children affected by obesity and ageing population at risk of malnutrition and non-communicable diseases (NCDs) b) screening of socioeconomic factors, lifestyle and dietary habits, environmental factors, food knowledge, nutritional status, body composition, functional status and disability, quality of life, genetic, metagenetic, phenotypic profiles, exposure to endocrine disruptors chemicals (EDCs), immune system functions in children and aging population with malnutrition c) human-derived biological samples analysis (including samples for the gut microbiome structure analysis and function).

Task 6.1.2.

Identification and application of biomarkers of malnutrition (including inflammatory, metabolic, microbiological, genetic and epigenetic ones) and biochemical pathways associated with diet and age-related diseases/ syndromes for early malnutrition detection and quality of life restoration in target specific categories.

Task 6.2.2.

Development and application of in vitro, in vivo and in silico experimental models for the understanding of the mechanism of action in counteracting malnutrition of new sustainable bioactive molecules from different matrices (in connection with Spoke 2, 3 and 4).

Task 6.3.1.

Assessing microbiome–host interaction in malnutrition (in connection with Spoke 4 and 5). a) Evaluation of gut microbiome features in paediatric and ageing subjects affected by malnutrition and malnutrition-related conditions, with a focus on immune and metabolic pathways; b) Investigation of gut microbiome cell wall constituents on immune and metabolic pathways involved in human malnutrition; c) Investigation of the diet, environmental factors and drugs influencing human gut microbiome structure and function; d) Design of an algorithm to predict the risk of gut dysbiosis associated with malnutrition and malnutrition-related diseases.

Task 6.4.1.

Implementation of sustainable dietary patterns as nutritional treatment for target specific groups with malnutrition. The task includes the prototyping of foods, supplements, ingredients and nutraceuticals aimed at restoring resilience in specific targets with malnutrition (in connection with Spoke 4). In addition, it is implemented a friendly end user personalised web responsive application for remote promoting and monitoring of sustainable dietary patterns target specific.

Task 6.4.2.

Preclinical and clinical evaluation of new prototypes of functional foods, food supplements, ingredients and nutraceuticals for preventing and treating malnutrition (in connection with Spoke 4).

Project deliverables

D6.1.1.1.

Systematic evaluation of existing data on nutritional status and critical issues for target specific groups with malnutrition (M8)

D6.1.2.1.

New biomarkers of malnutrition specific for diseases and age and related to diet (M24)

D6.1.2.2.

Identification of biochemical pathways interconnected with biomarkers of malnutrition and immunological responses (M36)

D6.2.2.2.

Identification of at least 7 sustainable bioactive molecules: a) 3 proven to directly impact nutritional status b) 2 proven to impact gut satiety hormones release c) 2 proven to reduce skeletal muscle mass decline in elderly populations with specific pathologies and/or nutritional impairments (M24)

D6.3.1.4.

Definition of a set of gut microbiome-derived molecules able to tackle gut dysbiosis, modulate immune response and metabolic pathways in specific targets with malnutrition. (M24)

D6.4.1.2.

New prototypes of functional foods, food supplements, ingredients and nutraceuticals for malnutrition and malnutrition related diseases (n=5) (M36)

D6.4.2.2.

Scaling up of innovative functional foods, food supplements, ingredients and nutraceuticals useful coadjuvant for malnutrition treatment (M30)

Interaction with other spokes

State of the art

The individual response to the diet results from fine-tuned physiological mechanisms that start-off during pregnancy and continue throughout the life. Preterm neonates display a high risk of postnatal malnutrition, especially at very low gestational ages, because of an imbalance of the nutritional stores in preterm infants. For this reason, nutrition and growth in early life play a pivotal role in the establishment of the long-term health of premature infants. In infant nutrition, the existing oversimplified dichotomy between natural-healthy breastmilk feeding and unhealthy processed infant formula can be tackled by the introduction of tailored chemical modifications in infant formulas and in fortifiers. In both formulas and fortifiers, protein glycation is almost unavoidable during processing, but not all the compounds formed possess deleterious physiological attributes. One of the smartest examples are represented by the Amadori compounds of lysine that in free form can be used by the gut microbiota leading to the formation of short chain fatty acids, well-known functional molecules able to play an active role in the case of infant malnutrition. Such evidence relies on the ability of gut microbiota to work as a bio-remediator and produce energy from the compounds formed during processing of foods (Wolf et al., Cell Host Microbe, 2019).

Operation plan

The two key targets are: 

  • to investigate how food processing and the protein modifications influence the ability of gut microbiota produce energy and functional molecules from non-canonical amino acids in malnourished infant; 
  • to decipher how metabolization products can promote the gut health through the synthesis of functional metabolites when fed with specific bioactive compounds. 

Metabolic pathways can be tracked investigating the fate of modified amino groups and bioactive molecules following an integrated approach:

1) the definition of specific modified side chains of amino acids building block, mimicking production process and chemical structures of peptides and proteins of infant formulas and human milk (HM) fortifiers; 
2) in vitro digestion protocols to define the kind of feeding material that reach the colon; 
3) untargeted mass spectrometry screening to identify functional metabolites and the microbial species of interest; 
4) construction of the metabolic pathways in presence of modified amino acids and HM fortifiers; 
5) evaluate the functional effects of such chemical modifications reviewing current recommendations by ESPHGAN and WHO and relevant literature to scale up new formulations.

Expected results

This strategy tackles challenges associated to newborns potentially exposed to malnutrition in an obesogenic environment or because of preterm delivery. As protein modifications is undeniably common during food processing and storage, we could provide solutions on how specific milk formulations and fortifiers impact the host/microbiota health status. A biochemical toolbox based on metagenomic, and metabolomics can address potential health issues for the general population. The expected results can provide a guidance in the field of food design focusing on previous evidence of the gut microbiota ability to produce energy from glycated amino acids. 
Expected results will cover:

  • identification of the metabolites formed and build the basis for a holistic picture of the impact on health;
  • demonstration of the ability of the gut microbiota to degrade modified amino acids and use fortifiers to produce functional metabolites;
  • definition of biochemical pathways tuned by HM fortifiers and by tailored protein modifications.