REVIEW PHYSIOLOGY 38: 42–50, 2023. First published September 20, 2022; doi:10.1152/physiol.00014.

2022

Precision Nutrition: Recent Advances in V. Saroja Voruganti

Department of Nutrition and Nutrition Research Institute, University
Obesity of North Carolina at Chapel Hill, Kannapolis, North Carolina
saroja@unc.edu

“Precision nutrition” is an emerging area of nutrition research that focuses on

understanding metabolic variability within and between individuals and helps de-
velop customized dietary plans and interventions to maintain optimal individual
health. It encompasses nutritional genomic (gene-nutrient interactions), epigenetic,
microbiome, and environmental factors. Obesity is a complex disease that is
affected by genetic and environmental factors and thus a relevant target of preci-
sion nutrition-based approaches. Recent studies have shown significant associa-
tions between obesity phenotypes (body weight, body mass index, waist
circumference, and central and regional adiposity) and genetic variants, epigenetic
factors (DNA methylation and noncoding RNA), microbial species, and environ-
ment (sociodemographics and physical activity). Additionally, studies have also
shown that the interactions between genetic variants, microbial metabolites, and
epigenetic factors affect energy balance and adiposity. These include variants in
FTO, MC4R, PPAR, APOA, and FADS genes, DNA methylation in CpG island
regions, and specific miRNAs and microbial species such as Firmicutes,
Bacteriodes, Clostridiales, etc. Similarly, studies have shown that microbial metab-
olites, folate, B-vitamins, and short-chain fatty acids interact with miRNAs to influ-
ence obesity phenotypes. With the advent of next-generation sequencing and
analytical approaches, the advances in precision nutrition have the potential to
lead to new paradigms, which can further lead to interventions or customized
treatments specific to individuals or susceptible groups of individuals. This
review highlights the recent advances in precision nutrition as applied to obe-
sity and projects the importance of precision nutrition in obesity and weight
management.

epigenetics; metabolic individuality; metabolomics; microbiome; nutrigenomics

Introduction
People have different responses to and requirements
for nutrients and other components of the diet, and
this heterogeneity is an important source of variance
in nutrition studies. Understanding this variation and
its role in risk for diseases has gained more momen-
tum with the advent of new tools and technologies
(1–3). “Precision nutrition” is an emerging area of nutri-
tion research that focuses on understanding meta-
bolic variability within and between individuals and
helps to develop customized dietary plans and inter-
ventions to maintain optimum individual health. It
assumes that each person will respond differently and
that their energy and dietary needs are different from
each other (3, 4). Using one’s DNA (genetics) to pre-
dict their response to nutrient intake is only one of the
various facets of precision nutrition. Other aspects
that influence the variation in individual response to
nutrients include epigenetic, microbiome, and envi-
ronmental factors (1, 4, 5).
The US National Institutes of Health (NIH) has recog-
nized and identified precision nutrition as a key area of
research in the pursuit of optimal health (6). As an an-
cillary study to their “All of Us” study, the NIH made a
substantial investment in precision nutrition research,
in recognition that one-size-does-not-fit all with respect
to dietary intake, metabolism, and disease risk (101).

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Precision nutrition can be categorized into personal-
ized or individualized nutrition and stratified nutrition,
the former being at an individual level whereas the lat-
ter one focusing on groups of susceptible individuals
(4, 7). Precision nutrition is innovative in that it consid-
ers individual differences in people’s genes, environ-
ment, and lifestyles. This information is key for
targeting treatments for specific group of individuals.
Advances in precision nutrition have led to, and con-
tinue to lead to, new discoveries that can provide the
foundations of interventions or treatments tailored to
specific individuals (7, 8).
Obesity is a major health concern worldwide (9–11).
It poses a considerable burden health-wise and cost-
wise. It is also a precursor to various other metabolic
diseases such as type 2 diabetes, cardiovascular dis-
eases, metabolic syndrome, neurodegenerative dis-
eases, and some types of cancers (12, 13). As per CDC
2017–2018 statistics, 42.4% and 9.2% of adults in the
United States have obesity and severe obesity,
respectively (102). The regulation of weight and me-
tabolism including the physiological processes has
been studied extensively. While the pathogenesis of
obesity seems as simple as the difference between
ingested and expended calories, scientific evidence
shows that obesity is a complex disease and involves
genetic, epigenetic, microbiome, psychosocial, and
environmental factors, as well as the interactions
between them. Additionally, a person’s social, cultural,
and behavioral factors also impact a person’s weight
and body composition (13, 14).
A key feature of obesity is the dysregulation of
energy metabolism. The central nervous system plays
a vital role in appetite, satiety, and energy regulation,
with the hypothalamus as the master regulator. The
arcuate nucleus (ARC), a part of the hypothalamus,
is a vital center for the regulation of metabolism and
feeding (15–17). It contains neurons that express two
distinct, functionally antagonistic, peptides; orexi-
genic [appetite stimulating: neuropeptide Y (NPY)
and agouti-related peptide (AgRP)] and anorexi-
genic [appetite suppressing: pro-opiomelanocortin
(POMC) and cocaine and amphetamine-regulated
transcript (CART)] peptides. The neuronal signals
from the lateral hypothalamus (increase food intake)
and parabrachial nucleus (decrease food intake) also
contribute to the regulation of appetite (18, 19). The pe-
ripheral signals include hormonal signals such as leptin,
insulin, and gut hormones [cholecystokinin (CCK), ghre-
lin, peptide YY (PYY), glucagon-like peptide1 (GLP1),
oxyntomodulin, obestatin, and nesfatin] (19, 20). The
integration of hormonal and nutritional signals from the
circulation and peripheral and central neuronal (includ-
ing astrocyte-neuron and microglia-neuron and gut-
brain axis) signals happens in the ARC to generate a
feeding response (15–17). Both components of energy
metabolism, energy intake and expenditure, have been
shown to be altered or modified by genetic
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variants and/or epigenetic modifications, micro-
bial species and metabolites, lifestyle, and social
and psychological factors, with serious implica-
tions for obesity (FIGURE 1) (15–17). This narrative
review highlights and discusses the recent advan-
ces in the components of precision nutrition in
relation to obesity.
Nutritional Genomics and Obesity
Nutritional genomics (NGx) is the study of how an indi-
vidual’s genetics affect the way nutrients are metabo-
lized (nutrigenetics) and how nutrients affect the way
genes are expressed (nutrigenomics) (8, 21). The main
aims of NGx are to identify genetic variants that are
associated with diet-related diseases, to underlie the
variability in responses to diet or nutrients, and to help
develop nutritional strategies that can treat or prevent
diseases (3, 8, 21). Among the metabolic diseases,
obesity is the most heavily studied within the NGx par-
adigm. It is well known that lifestyle factors such as
diet and exercise play a key role in the development
and treatment of obesity and related comorbidities.
However, it is also known that weight loss interven-
tions, whether dietary plans or exercise regimens, do
not elicit the same response from all individuals.
Additionally, the equation of energy in and energy out
is not as simple as it seems. The interindividual vari-
ability in response to diet or exercise is quite substan-
tial, even after correcting for differences in age,
gender, race/ethnicity, and sociodemographic charac-
teristics (3, 22, 23).
The imbalance between energy intake and
energy expenditure is a key determinant of obe-
sity. Energy intake occurs through intake of mac-
ronutrients, carbohydrates, proteins, and fats. The
amount and type of these macronutrients deter-
mine adiposity and energy equilibrium. A dynamic
time-series analysis of three decades of US data
and a decade of data from 164 other countries, af-
ter adjustment for total calories, has shown that
carbohydrate, and not fat, consumption was asso-
ciated with short- and long-term increases in
weight (24). Meta-analysis of studies of low-carbo-
hydrate and low-fat diets for weight loss showed
that, irrespective of total calories and weight loss,
reduction in carbohydrates may prove beneficial for
improving metabolic syndrome markers, including
obesity (25–27).
It is also known that simple or added sugars and sat-
urated fatty acids can adversely affect adiposity.
Simple sugars, such as glucose, fructose, lactose, and
sucrose, are metabolized differently than complex car-
bohydrates. As per the American Heart Association,
the recommended total sugar consumption for US
adults is 150 and 100 calories per day for men and
women, respectively (28). Although much decreased,
the consumption of simple sugars and saturated fatty
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acid remains higher than the recommended intake.
Both the monosaccharides glucose and fructose get
metabolized and yield great amounts of fat in the liver.
However, they differ in regional adipose deposition
with glucose promoting subcutaneous adipose deposi-
tion while fructose favors visceral adipose tissue depo-
sition (29). Other studies have shown the adverse
effects of simple sugars, either fructose or glucose, on
adiposity and weight gain (30–33). However, in a
recent study investigating the association between
macronutrient intakes and obesity and metabolic risk,
the authors did not find any link between carbohy-
drates, fats, and weight (34). These studies and results
show differences in the way nutrients affect obesity
phenotypes and point to the involvement of other bio-
logical and environmental factors.
Individual variability in weight phenotypes has a
strong genetic basis. Twin, family-based, and other
studies have estimated heritabilities of body com-
position and related phenotypes to be 40–70%
(35–38). Genome-wide association and candidate
gene studies have identified several genetic var-
iants that affect various components of obesity. In a
study of more than 300,000 European adults,
Locke et al. (39) identified 97 loci associated with
body mass index (BMI). Many of these loci, particu-
larly a specific set of 32 loci, have been consistently
reported to be associated with obesity across eth-
nicities. Some studies have generated polygenic risk
scores (PRS) from these 32 loci and found stronger
effects on anthropometric measures (40). The PRS is
computed from an independent set of polymorphisms
that are associated with the risk for a disease. The
total number of risk alleles per individual is summed,
weighted or unweighted by its effect size, and a score
is calculated. A single score, the PRS, thus reflects the
cumulative effect of the included polymorphisms and
is a better predictor of the disease risk (41, 42). A study

FIGURE 1. Individuality in metabolic response to diet/nutrition intake

Components of energy metabolism, energy intake and expenditure, have been shown to be altered or modified by genetic
variants and/or epigenetic modifications, microbial species and metabolites, lifestyle, and social and psychological factors,
with serious implications for obesity.

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in the UK Biobank has generated a PRS with 2.1 million
single nucleotide polymorphisms (SNPs) associated
with obesity and assessed them in individuals ranging
from birth to middle age (43).
Prominent among the genes that are associated
with appetite or adiposity are fat mass and obesity
related (FTO), melanocortin 4 receptor 4 (MC4R), apoli-
poprotein A5 (APOA5), neuropeptide Y (NPY), leptin
(LEP), leptin receptor (LEPR), brain-derived neurotro-
phic factor (BDNF), single-minded homolog1 (SIM1),
neurexin3 (NRXN3), NPC intracellular cholesterol
transporter 1 (NPC1), neuronal growth regulator q
(NEGR1), mitochondrial carrier homolog 2 (MTCH2),
apolipoprotein E (APOE), tumor necrosis factor alpha
(TNFa), plasminogen activator inhibitor 1 (PAI-1), trans-
membrane protein 18 (TMEM18), etc. (43–46). A study
investigating genetic influence on extreme obesity
found several loci that are linked to either the circa-
dian rhythm of food consumption or hypothalamic sig-
naling related to food intake (47, 48).
Studies have also shown differential effects of
nutrients based on an individual’s genetic makeup.
Genetic variants interact with nutrition and other envi-
ronmental factors such as physical activity to affect
obesity phenotypes. The most frequently studied
nutrients have been simple sugars and saturated and
unsaturated fatty acids. Simple sugars such as fruc-
tose and glucose, either in the form of sugar-sweet-
ened beverages (SSB) or as part of high fructose/
glucose diets, have been studied to understand their
effects on obesity and related comorbidities (49, 50).
In circulation, fructose and glucose have different met-
abolic fates, although fructose needs glucose for its
metabolic effects. Fructose, more than glucose, favors
hepatic lipogenesis (49). A large study including 6,934
women from the Nurses Health Study, 4,423 men
from the Health Professionals Follow-up Study, and
21,740 women from the Women’s Genome Health
Study generated a PRS, based on the aforementioned
32 obesity-associated SNPs. They found that with
an increment per 10 risk alleles, the relative risk for
BMI increased with every category of increasing SSB
intake (49). Some other examples of gene by diet
interactions with respect to obesity include carbohy-
drate intake and MC4R rs17782313 (51), low-protein
diet and genetic risk score (GRS) of 15 SNPs (52), satu-
rated fat intake and FTO (53), vitamin C intake and car-
boxy peptidase (CP) rs59465035 (54), fat and sugar
intake and taste receptor (TAS1R2) (55), 5 SNP PRS
and fried foods (56), high-fat hypocaloric diet and
resistin (RETN) rs10401670 (57), etc. (Table 1).
Weight loss interventions have also shown better
results when participant genetics were considered.
For example, a randomized controlled clinical trial,
The Nutrigenomics, Overweight/Obesity and Weight
Management (NOW) study conducted a weight loss
trial with two groups, one with a lifestyle balance pro-
gram and the other one with a lifestyle balance
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program with genetic testing. The latter group showed
better weight loss than the former one for as long as 6
months (59). Similar results were shown in another trial
that had 284 individuals who underwent a high-fat,
hypocaloric diet. They found greater weight loss in T
carriers of rs10401670 of RETN as compared to others
(57). Studies have also shown the effect of a few
genetic variants on the extent of weight loss in inter-
vention studies. A study by Franzago et al. (58) found
that A-allele carriers of rs9939609 of the FTO gene
lost less weight and decreased BMI less than TT car-
riers during a 12-mo diet/lifestyle intervention. A study
by Garaulet et al. (60) found that eating late was linked
to lower weight loss in AA genotype of PLIN1
14995 A > T carriers, thus pointing to the importance
of meal timing along with genes in obesity. On the
other hand, a 10-wk weight-loss intervention based on
35 SNPs did not find any difference between person-
alized dietary intervention based on 35 SNPs and a
generic healthy diet with respect to either loss of body
weight or fat mass (61).
In a similar vein, modified nutrient diets have been
linked to changes in the expression of genes associ-
ated with adiposity. In a collaborative cross mice
model, Yam et al (62) showed that genetic back-
ground and macronutrient alterations affected the
expression of genes involved in adiposity. There is an
increasing interest in intermittent fasting and its effect
on metabolic diseases including obesity. A study of
individuals with overweight/obesity showed a signifi-
cant decrease in FTO gene expression after the
month-long fasting period of Ramadan in contrast to
normal weight individuals (63).
Nutritional Epigenetics and Obesity
Epigenetics refer to the genetic effects that are exter-
nal to changes in DNA sequence. The various types of
epigenetic changes include DNA methylation (addi-
tion of methyl groups to cysteine or adenine on the
DNA), noncoding RNAs (short and long noncoding
RNAs that modulate mRNAs to affect gene expres-
sion), and histone modification (posttranslational modi-
fication of histone proteins that can affect chromatin
function and DNA accessibility) (64–66). A branch of
epigenetics, nutritional epigenetics, is the study of the
effects of food on the expression of genes (67).
Human and animal studies have shown that epige-
netic effects can transcend generations. Maternal
nutrition, in particular, can have distinct epigenetic
effects on the child’s risk for various metabolic dis-
eases (68–70).
An individual’s alleles are determined by their
maternal or paternal origins (genomic imprinting),
and these are involved in a variety of metabolic
functions. Alterations in genomic imprinting due to
epigenetic mechanisms such as DNA methylation,
histone modifications, or genetic events such as
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TABLE 1. Summary of nutrigenetics of obesity phenotypes
Variant of Nutrient/Dietary
Interest Gene Type of Study Sample Size Intake Outcome Population Conclusion Reference(s)

rs9939609 FTO Cohort 339,000 Total fat BMI European and TT allele of both SNPs asso- Corella et al. (53)
rs1121980 Hispanic adults ciated with higher BMI
with higher SFA intake
rs9939609 FTO Intervention 86 Mediterranean Weight loss Italian A allele was associated with Franzago et al.
diet less weight loss than TT (58)
carriers
rs662799 APOA5 Cohort 3266 Red meat Metabolic Korean G carriers and in highest ter- Choi and Shin,
syndrome tile of red meat consump- (103)
tion had 1.7 HR as
compared to those with A
allele
GRS of 4 SNPs Cohort 302 Total fat, SFA, Waist Ghana GRS >3 and high intake of Alsulami et al.
MUFA, and circumference fat, SFA, PUFA, and (52)
PUFA MUFA linked to increased
waist circumference
Fiber Body fat GRS >3 and high intake of
fiber had lower total body
fat as compared to low
fiber intake
GRS of 94 SNPs Cohort 362,496 Alcohol BMI UK adults (UK Increase in BMI per GRS is Rask-Anderson et
Biobank) higher in infrequent al. (104)
drinkers as compared to
frequent drinkers
rs6722579 CAB39 Cohort 50,808 Fat intake Abdominal Korea A carriers were at higher Kwon et al. (54)
obesity risk for abdominal obesity
in those who had fat
intake >DRI
rs59465035 CPQT T carriers are at lower risk
for abdominal obesity in
those who had vitamin C
>DRI
rs17782313 MC4R Cohort 282 Carbohydrate BMI Iranian Higher carbohydrate intake Alizadeh et al. (51)
intake was associated with
higher BMI and waist cir-
cumference in C carriers
rs1801282 PPARG Intervention 327 Diet therapy vs. Weight loss CC carriers had a greater Valeeva et al. (48)
diet therapy þ weight loss than others
metformin
rs59465035 CP Cohort 50,808 Vitamin C Waist Korean T-allele carriers had lower Kwon et al. (54)
circumference risk of abdominal obesity
as compared to others in
those who consumed
vitamin C higher than DRI
rs10401670 RETN Intervention 284 High-fat hypo- BMI Spain T-allele carriers had greater De Luis et al. (57)
caloric diet weight loss than others
5 SNP PRS Cohort >53,000 Fried foods BMI Korean High PRS and menarche Park et al. (56)
linked with higher BMI
rs1761667, CD36 Cohort 142 Fat and sugar BMI percentiles African American AA and altered fat percep- Primeaux et al.
intake females tion linked to BMI (55)
increase
rs35874116 TAS1R2 TT and sugar intake linked
to BMI increase
rs713598 TAS2R38 CC and energy intake linked
to BMI increase

GRS, genetic risk score; PRS, polygenic risk score; BMI, body mass index; SNP, single nucleotide polymorphism; SFA, saturated fatty acid; MUFA,
monounsaturated fatty acids; PUFA, polyunsaturated fatty acids; DRI, dietary reference intake.

translocation, inversion, duplication, etc., can result
in obesity (67). Animal studies have shown that pa-
ternal BMI at the time of conception can influence
an infant’s birth weight and patterns of DNA methyl-
ation in infant cord blood (71). Several studies have
evaluated the Dutch Famine Birth Cohort of the
Hunger Winter. These studies showed that intrauter-
ine exposure to maternal undernutrition results in
long-term effects on a child’s metabolic health,
including obesity, type 2 diabetes, and metabolic
syndrome (72, 73). Interestingly, these exposures
had long-term transgenerational effects. Similar
results were shown in studies using data from the
Chinese Famine that occurred between 1959 and
1961. Individuals born during this period reported
higher cases of obesity, type 2 diabetes, and meta-
bolic syndrome as compared to those born after the
famine (74, 75). In another human study, DNA col-
lected from infants born at term with 40 women of
normal BMI and with obesity revealed genomic loci
associated with differentially methylated regions
(DMRs) in CpG-dense regions (70). When compared
with another larger study, there was a significant
overlap in DMRs, with key genes being PTPRN2, a

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gene involved in insulin secretion, and MAD1L1, a gene
involved in cell cycle and tumor progression (70).
An intervention study that included 12 months of life-
style modification (Mediterranean diet and physical
activity) showed links between BMI and DNA methyla-
tion patterns. DNA methylation patterns in genes
related to lipid metabolism and inflammation were the
most modified by lifestyle interventions (65). In yet
another intervention study that involved a very-low-
calorie diet (VLCD), the investigators found that after a
VLCD therapy in individuals with obesity, DNA methyl-
ation patterns changed and resembled more those of
a normal weight person (76). In a cohort of normal-
weight and overweight-obese individuals, higher BMI
was associated with lower methylenetetrahydrofolate
reductase (MTHFR) gene methylation (77). Obesity-
associated alterations in methylation were also
observed in individuals on either weight-loss diets or
surgeries. In a group of individuals undergoing either
a very-low-calorie ketogenic diet (VLCKD), a balanced
hypocaloric diet (BHD), or bariatric surgery, DNA meth-
ylation in the angiotensin-converting enzyme (ACE2)
was higher in individuals with obesity as compared to
normal-weight individuals. VLCKD and BHDs helped
reverse this hypermethylation, but bariatric surgery
did not show a similar benefit (78).
Noncoding RNA, especially microRNAs (miRNA), is
another class of epigenetic markers that have been
linked to obesity and risk for other metabolic diseases
(79). These miRNA can affect mRNA stability and deg-
radation by binding anywhere along the length of the
mRNA transcript (80, 81). Like genetic variants, several
loci that correspond to miRNAs have been identified.
Kunej et al. (37) identified 1,736 genomic loci associ-
ated with obesity, of which 221 correspond to miRNAs.
Several studies have also found these miRNA to be
correlated with diet and lifestyle (82, 83), key ones
being miR-17/20/93, 21-590-5p, 200 b/c, 221/222, let-
7/miR-98, and miR-203 families of miRNAs. In a chil-
dren study, sex-specific association with obesity was
found with miRNAs, 26 b-3p, hsa-576-5p, hsa-31-5p,
hsa-10b-5p, and hsa-31-5p. (82). The understanding of
the human epigenome and its interaction with envi-
ronment, particularly diet, may provide greater insight
into the pathogenesis of obesity and help develop
personalized nutritional interventions.
Microbiome and Obesity
The human body contains millions of microbes that
can have significant health effects. The microorgan-
isms, collectively termed the microbiome, are from
bacterial, fungal, and protozoal origins (84). The com-
position of gut microbiota is influenced, to a greater
extent, by indigestible foods. The microbiota residing
in GI tracts prefer fermentable carbohydrates as sub-
strates whereas they use proteins and amino acids for
their own enzymes. The distant colon thus gains
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energy from fermented residual peptides and pro-
teins. The microorganisms residing in the gut have
been associated with obesity risk (85, 86). Individuals
with obesity have specific alterations in the compo-
sition and function of the gut microbiome (86–88),
and the gut microbiome affects energy balance by
affecting both energy utilization from the diet as
well as energy expenditures and storage. The
effects of gut microbiome on obesity phenotype
and weight loss have been captured through popu-
lation-based cohort studies as well as randomized
controlled trials (89, 90).
Studies have shown that individuals with obesity
have a greater amount of Firmicutes and higher
Firmicutes to Bacteriodes ratios (91). Other studies
have shown Firmicutes and Bacteriodes to be inver-
sely and positively associated with energy expendi-
ture and percent body fat, respectively (63). A recent
study by Depommier et al. (92) showed that pasteur-
ized Akkermansia muciniphila increased energy ex-
penditure and reduced body weight and fat mass in
diet-induced obesity in mice models. The same
groups showed that Akkermansia also improved gut
barrier integrity, insulin resistance, and dyslipidemia in
mice. They also translated these findings to humans in
an exploratory study where they found a reduction
in markers of liver dysfunction and inflammation after
supplementing the diet with Akkermansia (93). Similar
results have been shown in humans using other forms
of bacteria (88, 90, 93). In a study in normal weight
individuals with high and low visceral fat, the inves-
tigators found that a total of 16 species of microbes
were significantly correlated with visceral fat accu-
mulation as measured by quantitative computed to-
mography but not with BMI or waist circumference
(90). Of these Bacteriodes were associated with
low visceral fat. A longitudinal study of obesity con-
ducted in individuals undergoing laparoscopic
sleeve gastrectomy (LSG), found a negative correla-
tion between visceral fat and few microbial species,
the strongest being with Eubacterium eligens.
Before and after LSG analysis showed a significant
increase in specific species such as C. symbiosum,
C. hathewayi, C. citroniae, and other Clostridiales
after LSG (88). This is significant as Clostridiales are
considered to be “good” microbes and are nega-
tively associated with metabolic diseases (94).
The gut microbiota, whose genome is more than
100 times the human genome, are also known to pass
from the mother to the neonate through exposure dur-
ing delivery and through the breastfeeding (95). In
addition, the microbial metabolites such as short-chain
fatty acids, trimethylamine-N-oxide (TMAO), folate,
and other B vitamins, etc., are known to modulate epi-
genetic mechanisms including DNA methylation, his-
tone modifications, and noncoding RNAs (96, 97). The
microbiota is increasingly being recognized as a
potential synthesizer of biological compounds that
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can be used as epigenetic substrates or regulators of
epigenetic enzyme activity (98).
Conclusions
Precision nutrition is critical to formulating effective di-
etary plans customized for individuals or a group of
susceptible individuals of diverse ethnicities and pop-
ulations. To develop personalized or stratified dietary
plans, either to maintain optimal health or to treat met-
abolic diseases, there is a need to understand how an
individual responds to diet or nutrients and the factors
responsible for this variation in response. These areas
of nutrition fall under the purview of precision nutrition.
Knowledge of genetic variants affecting nutrient meta-
bolic pathways is not new but dates to the recognition
of phenylketonuria, lactase persistence, glucose phos-
phate dehydrogenase deficiency, etc. What is new is
that with the advent of next-generation sequencing
technologies and the latest analytical approaches, we
are now able to conduct a comprehensive investiga-
tion using ‘Omics’ approaches, which are revolutioniz-
ing the field. However, there are some issues that
need to be resolved before precision nutrition can be
put into practice. First, self-reporting approaches con-
tinue to be the primary methods for collecting dietary
data. Unless there is an objective approach to meas-
uring dietary intake, accurate estimates of dietary
intake (especially long term) will be difficult. Second,
there is a need to better integrate multiple sources of
data. Usage of machine learning approaches is help-
ing address the integration of multiple sources of
data. Third, proper flow of data among researchers,
practitioners, and educators is needed for dissemina-
tion or translation of these results. For example, physi-
cians and dietitian need proper training to be able to
prescribe genotype-guided diet plans to patients.
Fourth, proper counseling of patients is needed for
them to be able to comply with the personalized diet.
Despite all these caveats, incorporation of precision
nutrition approaches has started showing noteworthy
results.
In a study conducted by Connell et al. (99), research-
ers provided participants with personalized data-
driven dietary recommendations, using artificial intelli-
gence, and found significant improvement in clinical
outcomes in all conditions and disease activities.
Using dietary, genetic, and epigenetic data and
machine learning approaches, Lee et al. (100) identi-
fied 21 SNPs, 230 DNA methylation sites in lipid and
carbohydrate metabolism-related genes, and 26 die-
tary factors that predicted obesity with 70% accuracy.
The main goal of precision nutrition is to understand
the differences in the metabolic responses to diet/
nutrient intake between individuals and develop tai-
lored or customized nutritional plans for optimal
health. With the latest Omics and machine-learning-
based approaches, the future of precision nutrition,
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individualized or stratified, is bright and can be an
effective adjunct therapy to existing treatment strat-
egies. n
V. S. Voruganti is funded by the National Institute of
Diabetes and Digestive and Kidney Diseases Grants
R01DK126666 and P30DK056350, and Eunice Kennedy
Shriver National Institute of Child Health and Human
Development Grant UG1HD107692.
No conflicts of interest, financial or otherwise, are
declared by the authors.
V.S.V. conceived and designed research; V.S.V. drafted
manuscript; V.S.V. edited and revised manuscript; V.S.V.
approved final version of manuscript.
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