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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 ...

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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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...Introducing precision nutrition for vulnerable children in low resource settings paraskevi massara fell albeit with striking subnational heterogeneity however department of nutritional sciences faculty medicine globally million under years age were current programmatic university toronto ontario canada stunted and wasted approaches are mostly generic not tailored to regional james m njunge communal household or personal characteristics example the childhood acute illness chain while vitamin a zinc deficiency varies considerably network nairobi kenya kemri wellcome trust middle income countries this is usually considered research programme kilifi designing interventions such as composition ready use therapeutic foods used treat severe malnutrition deborah van den brink public health have been effective at scale where amsterdam umc location resources limited there likely be ceiling centre global child emma gains attainable from one size fits all approach s hospital netherlands could help...

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