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Introducing Precision Nutrition for Vulnerable Children in Low-Resource Settings
Introducing Precision Nutrition
for Vulnerable Children in
Low-Resource Settings
Paraskevi Massara fell, albeit with striking subnational heterogeneity. However, in
Department of Nutritional Sciences, Faculty of Medicine, 2020, globally 149 million children under 5 years of age were
1 Current programmatic
University of Toronto, Toronto, Ontario, Canada stunted and 45 million were wasted.
approaches are mostly generic, and not tailored to regional,
James M Njunge communal, household or personal characteristics. For example,
The Childhood Acute Illness & Nutrition (CHAIN) while vitamin A or zinc deficiency varies considerably in low-
Network, Nairobi, Kenya; KEMRI-Wellcome Trust and middle-income countries,2 this is not usually considered in
Research Programme, Kilifi, Kenya designing interventions such as the composition of ready-to-use
therapeutic foods used to treat children with severe malnutrition.
Deborah A van den Brink Such public health approaches have been effective at scale where
Amsterdam UMC location University of Amsterdam, resources are limited; however, there is likely to be a ceiling for
Amsterdam Centre for Global Child Health & Emma the gains attainable from a ‘one size fits all’ approach.
Children’s Hospital, Amsterdam, the Netherlands
“ Precision nutrition could help the
Wieger Voskuijl target populations of interventions
The Childhood Acute Illness & Nutrition (CHAIN) Network, where resources are limited”
Nairobi, Kenya; Amsterdam UMC location University of
Amsterdam, Amsterdam Centre for Global Child Health &
Emma Children’s Hospital, Amsterdam, the Netherlands; Appropriate nutrition is essential for growth, development and
Department of Paediatrics and Child Health, Kamuzu resilience, preventing diseases and their impacts. Ingested nutri-
University of Health Sciences, Blantyre, Malawi ents transit through metabolic pathways influenced by genetics,
James A Berkley epigenetics, the microbiome and environmental factors, contrib-
Department of Nutritional Sciences, Faculty of Medicine, uting to heterogeneity in individual needs and responses. These
University of Toronto, Toronto, Ontario, Canada; factors also underlie differences in disease susceptibility and
the CHAIN Network, Nairobi, Kenya; the KEMRI/Wellcome response to therapy. Thus, they have the potential to inform rec-
Trust Research Programme, Kilifi, Kenya; University of ommendations for different segments of populations (Figure 1)
Oxford, UK in precision nutrition approaches. Precision nutrition combined
with spatially resolved data could help the target populations of
Robert H J Bandsma interventions where resources are limited.3 Integration of big data
Department of Nutritional Sciences, Faculty of Medicine, related to genetic, epigenetic, microbiome, lifestyle and environ-
University of Toronto, Toronto, Ontario, Canada; mental factors is required to expand our understanding of the di-
the CHAIN Network, Nairobi, Kenya; the KEMRI/Wellcome versity of human metabolism in response to diet.
Trust Research Programme, Kilifi, Kenya The emerging role of precision nutrition
Precision nutrition encompasses utilizing a group or an individu-
Current nutritional interventional approaches al’s characteristics to optimize interventions. It is rapidly gaining
for vulnerable children traction, largely because of new ‘omics’ tools and consequent in-
Considerable effort has been made to improve nutrition among sights into the roles of the intestinal microbiome in metabolic and
vulnerable children, including those who are stunted and/or hormonal processes, and their association with diet. Differential
wasted. Between 2000 and 2015, child growth deficits in Africa responses to diet due to genetic and epigenetic factors (‘nutrige-
29 Sight and Life Special Report / The Evidence Base
Introducing Precision Nutrition for Vulnerable Children in Low-Resource Settings
figure 1: The mu ltilevel role of precision nutrition to prevent and manage disease
Social Clinical Metabolic Genetic Microbiome Global
Region
Community
Household
Individual
netics’) are increasingly recognized. For example, malnutrition potentially require feeds with a different lipid composition.7 How-
in all its forms (undernutrition, micronutrient deficiencies, over- ever, in general, local preferences have informed the composition
1 influences DNA methylation, affecting host
weight or obesity) of therapeutic feeds in some countries including Bangladesh,
metabolism.4 Metabolites of the microbiota, such as short-chain Vietnam and India to increase acceptability.8−10
fatty acids, can also alter DNA methylation and histone acetyla-
tion, potentially affecting epigenetic regulation of metabolic pro- Intestinal microbiota
cesses.5 Clinical status and social factors also offer the potential to The intestinal microbiota lives symbiotically within the host, har-
target approaches. For example, integrating anthropometry, diet, boring ~100-fold more genes than the host. Its composition and
physical activity and microbiome can accurately predict glycemic function are shaped by gestational age, birth mode, genetics, epi-
response to a meal.6 genetics, feeding, antimicrobials and the environment. Diet is a
key driver of variation in constituent organisms and their func-
11−16 The intestinal microbiota influences
“ Identifying food components that tional gene content.
improve beneficial functions of the human development and homeostasis by modulating immune
17,18 metabolism19,20 and energy ho-
regulation, gut integrity,
microbiota is a potential dietary meostasis, brain function and pathogen colonization resistance.21
approach to enhancing precision” Thus, the microbiota is an intermediary between nutrition and
health, and an important target for precision nutrition-based in-
terventions.
Undernutrition has been associated with an ‘immature’ micro-
Feeds for severe malnutrition biota phenotype that is largely refractory to current nutritional
Two milk-based formulae – F-75 (lower protein, lower energy) interventions.22,23 Dysbiosis24,25 (altered microbiota composi-
and F-100 (higher protein and higher energy) – are used to treat tion or function) likely interferes with processes essential for host
children with severe malnutrition in the stabilization and reha- health and wellbeing. Identifying food components that improve
bilitation phases of inpatient treatment, respectively. The World beneficial functions of the microbiota is a potential dietary ap-
Health Organization recommends ready-to-use therapeutic foods proach to enhancing precision. Microbiota-directed feeds using
that have a similar nutritional composition to F-100 for commu- readily available foods such as chickpea, soy, peanut and banana
26,27 Since both
nity-based management of severe malnutrition in a single reha- can alter the microbiome, promoting weight gain.
bilitation phase. While these feeds are critical, their composition, composition and targets may vary regionally, such precision nutri-
amounts and duration have not been customized to meet the in- tion approaches have the potential to radically change strategies
dividualized needs. Variability in energy requirements may need and may optimize benefits, given resource limitations.
to be addressed, and proteomics and metabolomics studies have Functional readouts of the microbiome can assess the effects
demonstrated that HIV-infected children with severe malnutrition of nutritional approaches. For example, short-chain fatty acids
Sight and Life Special Report / The Evidence Base 30
Introducing Precision Nutrition for Vulnerable Children in Low-Resource Settings
are bacterial fermentation compounds of dietary fibers that play markers and volatile organic compounds are associated with poor
a role in immune regulation.28 Poorly digested fibers can lead 37−40 Both are a proxy for sys-
outcomes in severe malnutrition.
to the accumulation of pro-inflammatory metabolites.29 There- temic inflammation and altered microbiota, and could be devel-
fore, assessing an individual’s fiber digestive capacity could lead oped as a near-bedside point-of-care tool.
to differential nutritional recommendations for poor versus high
fiber-digesters. Microbiome-dependent metabolism of pharma- Tools for precision nutrition
ceutical compounds can also be assessed to optimize treatment Longitudinal growth analyses
30,31 For example, the relationship between metformin
responses. Longitudinal growth monitoring is essential for the evaluation of
and the microbiome is partially responsible for its beneficial ef- children’s nutritional and health status.41 Thus, growth pathways
fects on lifespan.32 Thus, reshaping host–microbiota interactions constructed using longitudinal measurements are an important
through precision nutrition is a new therapeutic avenue for both tool for assessing growth longitudinally at both individual child
disease control and prevention, and could be harnessed to affect 42,43 The shapes of growth trajectories
level and population level.
functional/clinical outcomes including immune function, cogni- have been associated with health outcomes such as cardiometa-
tion and growth. bolic health.44 Thus, it is possible to predict growth and therefore
to design targeted interventions for individual children through
Risk prediction for precision nutrition precision nutrition.
Clinical parameters that are collected routinely in nutritionally
and clinically vulnerable children can be harnessed to guide more Systems thinking
precise nutritional management (Figure 2). Studies in intensive The role of nutrition in vulnerable children is multifaceted.
care units in high-resource settings demonstrate that limiting ca- Systems thinking provides the framework to study the interre-
33 Ide- lationships between elements of the system and the function of
loric intake during critical illness can improve outcomes.
ally, nutritional intake should be based on individual basic energy the system as a whole.45 Potential advantages of system-based
needs, but stratified approaches may be feasible with improved approaches include reducing inequities in health research and
knowledge of energy requirements for malnourished children policymaking. This can be achieved by modeling complex social
with different levels of clinical illness severity. Clinical warning interactions between different communities46,47 and bridging
signs provide an opportunity to identify changes which occur the gap between research and practice by the potential impact of
daily that can be used to stratify children to alternative nutritional implementing an intervention.48 Figure 3 shows an application
and medical treatments (Figure 2).34−36 Specific metabolic bio- of systems thinking.
figure 2: Biomar kers and clinical warning signs can be used to stratify patients and to monitor and evaluate a treatment plan,
resulting in treatment more tailored to the individual’s needs
CLINICAL WARNING SIGNS BIOMARKERS
∙ Triage scores ∙ Volatiles
∙ Continous monitoring ∙ Metabolomics
∙ Individual parameters
Precision treatment based on
current needs of the child
31 Sight and Life Special Report / The Evidence Base
Introducing Precision Nutrition for Vulnerable Children in Low-Resource Settings
figure 3: Precision nu trition for vulnerable children in low-resource settings from the systems thinking perspective
Education
Employment Media
consumption
Public health
policies
Food Sociodemographics Cost of
production physical activity
Cost of the Diet Diet Physical Domestic Physical activity
ingredients quality activity physical activity infrastructures
Supplement Individual Recreational
availability physical activity
Genetic
makeup
Digestion Gut
and absorption microbiome
Metabolic
response
References
“ Tailoring interventions to actual 1 WHO . The UNICEF/WHO/World Bank Group Joint Child Malnutrition
Estimates (JME) group released new data for 2021. Internet:
needs may be cost-effective” https://www.who.int/news/item/06-05-2021-the-unicef-who-wb-
joint-child-malnutrition-estimates-group-released-new-data-for-2021
In summary, new tools and approaches allow us to identify (accessed 24 September 2022).
groups in whom interventions can be targeted to optimize benefit, 2 Zhao T , Liu S, Zhang R, Zhao Z, Yu H, Pu L, et al. Global Burden of
thus introducing a precision nutrition approach to public health Vitamin A Deficiency in 204 Countries and Territories from 1990-
nutrition. Resource limitations in low- and middle-income coun- 2019. Nutrients. 2022 Mar;14(5):950.
tries are a major factor dictating programs and policy; however, 3 Osgo od-Zimmerman A, Millear AI, Stubbs RW, Shields C, Pickering BV,
tailoring interventions to actual needs may be cost-effective, and Earl L, et al. Mapping child growth failure in Africa between 2000
this needs to be assessed in robust clinical trials. and 2015. Nature. 2018;555(7694):41–7.
4 Quilter CR, Harvey KM, Bauer J, Skinner BM, Gomez M, Shrivastava
M, et al. Identification of methylation changes associated with
Correspondence: Dr James A Berkley, positive and negative growth deviance in Gambian infants using a
Kenya Medical Research Institute/Wellcome Trust Research targeted methyl sequencing approach of genomic DNA. FASEB Bioadv.
Programme, Kilifi 80108, Kenya 2021;3(4):205–30.
Email: jberkley@kemri-wellcome.org 5 Li D , Li Y, Yang S, Lu J, Jin X, Wu M. Diet-gut microbiota-epigenetics
in metabolic diseases: From mechanisms to therapeutics. Biomed
Dr Robert H J Bandsma, Pharmacother. 2022 Jun;153:113290.
Departments of Paediatrics and Nutritional Sciences, 6 Zeevi D, Korem T, Zmora N, Israeli D, Rothschild D, Weinberger A,
University of Toronto, 555 University Avenue Toronto, et al. Personalized nutrition by prediction of glycemic responses. Cell.
Ontario, Canada 2015;163(5):1079–94.
Email: robert.bandsma@sickkids.ca 7 Gonzales GB, Njunge JM, Gichuki BM, Wen B, Potani I, Voskuijl,
W et al. Plasma proteomics reveals markers of metabolic stress
Sight and Life Special Report / The Evidence Base 32
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