ReviewAllergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology2014
The potential mechanistic link between allergy and obesity development and infant formula feeding.
Review in Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Protein Intake from Birth to 2 Years and Obesity Outcomes in Later Childhood and Adolescence: A Systematic Review of Prospective Cohort Studies.Advances in nutrition (Bethesda, Md.) · 2021Pooled it
- Lower Protein Intake Supports Normal Growth of Full-Term Infants Fed Formula: A Randomized Controlled Trial.Nutrients · 2018Trial
- Exosome-Derived MicroRNAs of Human Milk and Their Effects on Infant Health and Development.Biomolecules · 2021Review
- Review
- Introduction of fish and other foods during infancy and risk of asthma in the All Babies In Southeast Sweden cohort study.European journal of pediatrics · 2019Article
- Comment on "Early introduction of complementary foods and childhood overweight in breastfed and formula-fed infants in the Netherlands: the PIAMA birth cohort study".European journal of nutrition · 2018Article
- Response to letters to the editor regarding our paper "Early introduction of complementary foods and childhood overweight in breastfed and formula-fed infants in the Netherlands: the PIAMA birth cohort study".European journal of nutrition · 2018Article
- Milk's Role as an Epigenetic Regulator in Health and Disease.Diseases (Basel, Switzerland) · 2017Review
- Application of the adverse outcome pathway (AOP) concept to structure the available in vivo and in vitro mechanistic data for allergic sensitization to food proteins.Clinical and translational allergy · 2017Review
- Pervasive promotion of breastmilk substitutes in Phnom Penh, Cambodia, and high usage by mothers for infant and young child feeding.Maternal & child nutrition · 2016Article
- Milk: a postnatal imprinting system stabilizing FoxP3 expression and regulatory T cell differentiation.Clinical and translational allergy · 2016Review
- Early redox imbalance is associated with liver dysfunction at weaning in overfed rats.The Journal of physiology · 2015Article
- CD4(+), CD25(+), FOXP3 (+) T Regulatory Cell Levels in Obese, Asthmatic, Asthmatic Obese, and Healthy Children.Inflammation · 2015Article
- Milk--A Nutrient System of Mammalian Evolution Promoting mTORC1-Dependent Translation.International journal of molecular sciences · 2015Review
- Milk consumption during pregnancy increases birth weight, a risk factor for the development of diseases of civilization.Journal of translational medicine · 2015Review
- Early Programming by Protein Intake: The Effect of Protein on Adiposity Development and the Growth and Functionality of Vital Organs.Nutrition and metabolic insights · 2015Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This article provides a new view of the cellular mechanisms that have been proposed to explain the links between infant formula feeding and the development of atopy and obesity. Epidemiological evidence points to an allergy- and obesity-preventive effect of breastfeeding. Both allergy and obesity development have been traced back to accelerated growth early in life. The nutrient-sensitive kinase mTORC1 is the master regulator of cell growth, which is predominantly activated by amino acids. In contrast to breastfeeding, artificial infant formula feeding bears the risk of uncontrolled excessive protein intake overactivating the infant's mTORC1 signalling pathways. Overactivated mTORC1 enhances S6K1-mediated adipocyte differentiation, but negatively regulates growth and differentiation of FoxP3(+) regulatory T-cells (Tregs), which are deficient in atopic individuals. Thus, the "early protein hypothesis" not only explains increased mTORC1-mediated infant growth but also the development of mTORC1-driven diseases such as allergy and obesity due to a postnatal deviation from the appropriate axis of mTORC1-driven metabolic and immunologic programming. Remarkably, intake of fresh unpasteurized cow's milk exhibits an allergy-preventive effect in farm children associated with increased FoxP3(+) Treg numbers. In contrast to unprocessed cow's milk, formula lacks bioactive immune-regulatory microRNAs, such as microRNA-155, which plays a major role in FoxP3 expression. Uncontrolled excessive protein supply by formula feeding associated with the absence of bioactive microRNAs and bifidobacteria in formula apparently in a synergistic way result in insufficient Treg maturation. Treg deficiency allows Th2-cell differentiation promoting the development of allergic diseases. Formula-induced mTORC1 overactivation is thus the critical mechanism that explains accelerated postnatal growth, allergy and obesity development on one aberrant pathway.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.