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Recent Advance in Infant Nutrition: Human Milk Oligosaccharides

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Breast feeding and human milk are the standards for infant feeding and nutrition. Human milk oligosaccharides (HMOs) are the third most abundant solid component in human milk. To date, more than 200 structural different HMOs have been identified and some can be synthesized by the food industry. HMOs are one of the major differences between human milk and formula milk, and current evidence demonstrates their various beneficial effects toward infants’ health: acting as anti-adhesive antimicrobials, immune modulators, and intestinal cell response modulators, as well as providing prebiotics effect and neurodevelopment and cognition effects. HMOs compositions vary among mothers, influenced by the stage of lactation, duration of pregnancy and maternal genetic factors. However, there are still some unknown factors affecting the compositions of HMOs and requiring further research for clarification. A combination of preclinical and clinical cohort studies may help to identify whether an individual HMO contributes to disease protection. In recent years, 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT) have been approved as food ingredients by official authorities. Infant formulae supplemented with these HMOs are well-tolerated. However, more prospective clinical studies are warranted to elucidate HMOs' significance in infant nutrition. Breast milk feeding remains the best option for infants nutrition and development. Whenever breast milk is not adequate or unavailable, infant formula supplemented with HMOs might be considered as an alternative.
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Review Article
Recent advance in infant nutrition: Human
milk oligosaccharides
Yu-Jyun Cheng
a
, Chun-Yan Yeung
b,c,
*
a
Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hsinchu MacKay Memorial
Hospital, Hsinchu, Taiwan
b
Department of Gastroenterology, Hepatology and Nutrition, MacKay Children’s Hospital, Taipei,
Taiwan
c
Department of Medicine, MacKay Medical College, New Taipei City, Taiwan
Received Jul 11, 2020; received in revised form Dec 15, 2020; accepted Dec 28, 2020
Available online ---
Key Words
breast milk;
human milk
oligosaccharides;
immune modulators;
infant formula;
infant nutrition
Breast feeding and human milk are the standards for infant feeding and nutrition. Human milk
oligosaccharides (HMOs) are the third most abundant solid component in human milk. To date,
more than 200 structural different HMOs have been identified and some can be synthesized by
the food industry. HMOs are one of the major differences between human milk and formula
milk, and current evidence demonstrates their various beneficial effects toward infants’
health: acting as anti-adhesive antimicrobials, immune modulators, and intestinal cell
response modulators, as well as providing prebiotics effect and neurodevelopment and cogni-
tion effects. HMOs compositions vary among mothers, influenced by the stage of lactation,
duration of pregnancy and maternal genetic factors. However, there are still some unknown
factors affecting the compositions of HMOs and requiring further research for clarification. A
combination of preclinical and clinical cohort studies may help to identify whether an individ-
ual HMO contributes to disease protection. In recent years, 20-fucosyllactose (20-FL) and lacto-
N-neotetraose (LNnT) have been approved as food ingredients by official authorities. Infant
formulae supplemented with these HMOs are well-tolerated. However, more prospective clin-
ical studies are warranted to elucidate HMOs’ significance in infant nutrition. Breast milk
feeding remains the best option for infants nutrition and development. Whenever breast milk
is not adequate or unavailable, infant formula supplemented with HMOs might be considered
as an alternative.
ª2021 Published by Elsevier Ltd.
* Corresponding author. Department of Pediatric Gastroenterology, Hepatology and Nutrition, MacKay Children’s Hospital, MacKay Medical
College, No. 92, Sec. 2, ChungShan N. Rd, Taipei, 104, Taiwan.
E-mail address: cyyeung@mmh.org.tw (C.-Y. Yeung).
+MODEL
Please cite this article as: Y.-J. Cheng and C.-Y. Yeung, Recent advance in infant nutrition: Human milk oligosaccharides, Pediatrics and
Neonatology, https://doi.org/10.1016/j.pedneo.2020.12.013
https://doi.org/10.1016/j.pedneo.2020.12.013
1875-9572/ª2021 Published by Elsevier Ltd.
Available online at www.sciencedirect.com
ScienceDirect
journal homepage: http://www.pediatr-neonatol.com
Pediatrics and Neonatology xxx (xxxx) xxx
1. Introduction
Human milk is recommended as the best source for infant
nutrition in the first six months of life and should be
continued with addition of complementary food.
1
The
current evidence supports the health benefits of breast
feeding, such as decreased mortality and prevention of
acute illness (diarrhea, upper respiratory tract infection
and otitis media, etc.). Furthermore, the probable re-
ductions in overweight and maternal protection against
breast cancer have also been emphasized.
1,2
The composition of breast milk is complex and dynamic,
consisting of macronutrients (carbohydrate, protein and
fat), micronutrients (calcium, thiamine, zinc, etc.), hor-
mones, insulin-like growth factor-1 and cytokines. Human
milk oligosaccharides (HMOs), the third most abundant solid
component in human milk, are resistant to digestion in
upper small intestine and the majority of HMOs reach the
large intestine.
3
HMOs have many health benefits including
modification of intestinal microbiota, protection against
infection and inflammation, immunomodulation and pre-
vention of necrotizing enterocolitis (NEC) in prematurity.
This narrative review aims to summarize the current
knowledge toward HMOs and update the clinical experience
and evidence of HMOs on infant health.
2. What are HMOs?
In the early twentieth century, the mortality rate of infants
in the first year of life was as high as 20e30%.
4
It was
observed that the breast-fed infants had higher survival
rates than bottle-fed infants. Also, fecal bacterial differ-
ence was found between infants fed breast milk and bovine
milk. Carbohydrates were believed to play an important
role in the fecal bacterial composition. In addition to
lactose, human milk contained an unknown carbohydrate
fraction. Until 1930, this was termed “Gynolactose” and
two decades later, in 1954, its role as bifidogenic factor in
human milk was confirmed.
4,5
This bifidogenic factor was
later renamed as HMO. Owing to advances of food science
and biotechnology, more than 200 structures of HMOs have
been identified and some can be industrially produced.
HMOs are non-digestable carbohydrates, ranging from 20
to 25 g/L for colostrum and 5e15 g/L for mature human
milk.
5
They are not affected by pasteurization and freeze-
drying.
6
The basic structure of HMO contains a lactose base,
elongating by N-acetyllactosamine units with further fuco-
sylation and/or sialylation, which provides great structural
diversity in HMOs (Fig. 1). There are three major categories
of HMOs: (i) fucosylated neutral HMOs (35%e50%), (ii) non-
fucosylated neutral HMOs (42%e55%), and (iii) sialylated
acidic HMOs (12%e14%). The neutral HMOs account for
more than 75% of the total HMOs in human breast milk and
20-fucosyllactose (20-FL), a trisaccharide consisting of
glucose, galactose and fucose, is the most abundant HMO
accounting for almost 30% of all HMOs. Various factors in-
fluence HMOs concentrations, such as stage of lactation,
maternal genetic profile including secretor and Lewis blood
group status, and the duration of pregnancy.
7
The level of
HMOs is highest in the colostrum and decreases over the
course of lactation. Preterm milk contains lower levels of
fucosylated HMOs compared with mature milk and the level
increases with gestational age.
8
This might because fuco-
sylation is not well regulated in prematurity.
9
The HMOs
compositions mirror blood group characteristics, the Lewis
antigen system, determined by the activity of two gene loci
encoding for the a1-2-fucoslyltransferase (FUT2, encoded
by the Se gene) and the a1-3/4-fucosyltransferase (FUT3,
encoded by the Le gene). The secretor (Se) gene which
encodes for FUT2 is crucial to the synthesis of 20FL and
other a1-2-fucosylated HMOs. Therefore, milk of secretor
women is abundant in 20FL, lacto-N-fucopentaose I (LNFP I)
and other a1-2-fucosylated HMOs. On the contrary, non-
secretors lack a functional FUT2 enzyme and their milk
does not contain a1-2-fucosylated HMO. This could explain
why total amounts of HMOs in secretor mothers are higher
than non-secretors.
7
Thus, breast milk can be assigned into
four groups: Lewis positive secretors (Le þSeþ), Lewis
negative secretors (Le-Seþ), Lewis positive non-secretors
(Le þSe-) and Lewis negative non-secretors (Le-Se-)
(Table 1)(Fig. 1).
5,7,10
The secretor status of mothers can be assessed by saliva
test or directly genotyping the FUT2 gene.
11
The secretor
status varies geographically, leading to the differences of
corresponding HMOs (Table 2).
11e20
More than 90% of
mothers were secretors in Latin America and the western
United States. On the contrary, the frequency of non-
secretors was higher in Europe, Africa and East Asia.
13
In
Asia, around 50e80% of Chinese mothers were secretors
12,16
and this proportion was 70% in Vietnamese mothers.
17
In
Taiwan, previous data showed that secretor mothers
ranged from 83% to 100%.
18e20
However, this association of
genetic background and HMO composition (Table 1) might
not reflect the real situation in some populations. For
example, some a1-2-fucosylated HMOs have been found in
the milk of non-secretor mothers who did not express Se
gene. This may imply that other fucoslytransferases were
involved in HMOs formation.
21
In addition, previous data
showed that there was a subgroup of secretors, the weak
secretor phenotype, expressing both Lewis a and Lewis b
antigen. This phenotype was rarely seen in Caucasians but
it was commonly found in Polynesians and East
Asians.
18e20,22
Interestingly, the HMOs of Samoan women
had a particularly low level of 2-fucosylated components
such as 20-FL, lacto-N-fucopentaose I (LNFP I) and lacto-N-
difucohexaose I (LNDFH I). It is likely that the composition
of fucosylated HMOs of Samoan women were similar to the
“non-secretor” mothers.
23
This discrepancy could be
explained by the relatively low activity of a1-2-
fucoslyltransferase in this weak secretor population.
Hence, further studies are warranted to further clarify the
real world populations of secretors and their associations
with HMOs composition.
3. Functions and health benefits of HMOs
Various studies have corroborated the beneficial effects of
HMOs (Table 3). HMOs have been considered as bioactive
prebiotics that resist digestion by human enzymes and
promote the growth of beneficial bacteria.
5,24
For example,
Bifidobacterium longum subsp. infantis (B. infantis) grows
well on HMOs as the only source of carbohydrates.
25,26
Y.-J. Cheng and C.-Y. Yeung
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There are also other species of bifidobacteria that show the
ability to utilize HMOs as growth factors.
27
The growth of
bifidobacteria produces short-chain fatty acids that help to
create an environment favoring the growth of beneficial
bacteria rather than potential pathogens.
28
In addition, HMOs have been considered more than
“food for bugs ˮ.
5
It is supposed that in the evolution of
milk, oligosaccharides may play a role in the antimicrobial
defensive system.
29
Studies have shown that some specific
HMOs can directly inhibit the growth of group B strepto-
coccus (GBS), a leading cause of invasive bacterial infection
in newborns, which is typically acquired vertically during
childbirth secondary to maternal vaginal colonization.
30
Furthermore, HMOs can modulate the growth and biofilms
formation of GBS. Under high-resolution scanning electron
microscopy, cell arrangement perturbation of the biofilm
was observed in bacterial culture treated with specific
HMOs.
31
The findings suggest HMOs’ bacteriostatic effect in
a way that impairs bacterial growth kinetics.
HMOs also have antiadhesive effect. Various pathogens
such as viruses, bacteria and parasites need to adhere to
the mucosal surfaces to colonize or invade to cause dis-
ease. HMOs can serve as decoy receptors that prevent mi-
crobes binding to epithelial cells. Animal studies showed
that HMOs inhibited Campylobacter colonization.
32
In
addition, further cohort studies also revealed protection
against infectious diarrhea.
33
Another HMO, lacto-N-
neotetraose (LNnT), when administered with pneumo-
coccus intratracheally, could attenuate the course of
pneumococcal pneumonia and prevent nasopharyngeal
colonization in animal model study.
34
In addition to influencing the composition of gut micro-
biota, HMOs also directly modulate host intestinal epithelial
cell responses. HMOs reduce cell growth, and induce differ-
entiation and apoptosis in human intestinal cells.
35,36
Studies
also showed that some HMOs promoted maturation of intes-
tinal cells and increased the barrier function.
37,38
Another
important function of HMOs is immunomodulation. HMOs
Figure 1 Basic HMOs structure (A) HMOs are composed of 5 different building blocks (monosaccharides): glucose (Glc), galactose
(Gal), N-acetylglucosamine (GlcNAc), fucose (Fuc), and sialic acid (Sia). All HMOs contain lactose at the reducing end. Lactose can
be elongated by the addition of the disaccharides lacto-N-biose (Galb1e3GlcNAc) or N-acetyllactosamine (Galb1e4GlcNAc).
Lactose or the elongated oligosaccharide chain can be fucosylated in a1-2, a1-3 or a1-4 linkage and/or sialylated in a2-3 or a2-6
linkage (B)Fucosylated/Non-fucosylated (neutral) HMO (C) Sialylated (acidic) HMOs.
Pediatrics and Neonatology xxx (xxxx) xxx
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3
directly affect immune cells systemically after being absor-
bed into the blood and indirectly modulate immune responses
by altering the gut microbiota.
39,40
After ingestion, most
HMOs resist the intestinal digestion andreach the distal small
intestine and colon.
41
However, around 1% of the ingested
HMOs are absorbed and detected in the systemic circulation
and urine.
42
Although the exact mechanism of HMOs absorp-
tion into bloodstream was not fully understood, studies
showed that HMOs exerted systemic effects by binding of
monocytes, lymphocytes, and neutrophils to endothelial
cells.
43
HMOs directly affect intestinal epithelial cells and
regulate their gene expression, leading to changes in cell
surface glycans and other cell responses. HMOs can also
modulate lymphocyte cytokine production, potentially
leading to a more balanced Th1/Th2 response.
44
20-FL, a
major component of HMO, directly inhibits
lipopolysaccharide-mediated inflammation during
enterotoxigenic Escherichia coli invasion of T84 (modeling
mature) and H4 (modeling immature) intestinal epithelial
cells through attenuation of CD14 induction. CD14 expression
mediates the lipopolysaccharide-Toll-like receptor 4 stimu-
lation of a part of the “macrophage migration inhibitory
factors” inflammatory pathway by suppressing the cytokine
signaling 2/signal transducer and activator of transcription
factor 3/nuclear factor-kB.
45
Furthermore, HMOs impact
neurodevelopment and cognitive function. In animal studies,
oral supplementation of 20FL enhanced memory and
learning.
46
In human cohort studies, greaterearly exposure to
20FL could also contribute to infant cognitive development.
47
In addition, metabolic products of HMOs, like sialic acid, can
promote brain development, neuronal transmission and
synaptogenesis.
48,49
4. HMOs and preterm infants
NEC is one of the most common fatal diseases in neonates,
affecting 5e10% of very low birth weight infants.
50,51
The
mortality rate could be as high to 20e30% in those who
required surgical intervention.
51,52
NEC is associated with
long-term morbidities such as malabsorption, failure to
thrive and neurodevelopmental delays.
52
Previous studies
showed that preterm infants who were fed exclusively
human milk had 6 to 10 times less NEC compared to
formula-fed infants.
53e55
HMOs are thought to contribute
to the lower incidence of NEC. The protective efficacy of
HMOs from a neonatal rat NEC model showed that pooled
HMOs significantly improved survival and reduced NEC pa-
thology scores.
56
Further multidimensional chromatog-
raphy analysis identified a specific HMO, disialyllacto-N-
tetraose (DSLNT), as most effective in protecting against
NEC.
56,57
This effect was so highly structure-specific that
enzymatic removal of just one sialic acid from DSLNT could
lead to loss of function.
56
In a multicenter clinical pro-
spective cohort study on 200 mothers and their VLBW in-
fants that were predominantly human milk-fed, the
researchers analyzed HMOs composition in human milk fed
to infants over the first 28 days postpartum and compared
all eight NEC cases with controls.
58
The total HMO con-
centration did not differ considerably between cases but
DSLNT concentrations were significantly lower in NEC cases
and its abundance could identify NEC cases prior to onset.
Furthermore, the extent of deficiency worsened in accor-
dance with Bell’s stage. The combination of preclinical
animal model studies and clinical cohort studies not only
supports the hypothesis of a protective effect from HMOs
but also implies that low DSLNT concentrations in the
Table 1 The genetic background and associated HMOs.
Groups of
HMOs
Lewis Gene
(FUT3)
Secretor Gene
(FUT2)
Phenotypes Associated
HMOs
I(þ)(þ) Lewis Positive Secretor Secret all HMOs
II (þ)() Lewis Positive non-Secretor LNT, LNFP-II, LNFP-III, LNDFH II
III ()(þ) Lewis Negative Secretor 20FL, 3FL, LNFP-I, LNFP-II
IV ()() Lewis Negative non-Secretor 3FL, LNT, LNFP-III, LNFP-V
20-FL: 20-fucosyllactose; 30-FL: 30-fucosyllactose; LNT: Lacto-N-trtraose; LNFP: lacto-N-fucopentaose; LNDFH II: lacto-N-difucohexaose II.
Table 2 Geographical distribution of secretors.
Area Percentages of
Secretors
References
cited
Europe
Sweden 79% [13]
Spain 76% [13]
Italy 76% [15]
America
United states of
America
68e95% [12,13]
Mexico 99% [12e14]
Peru 98% [13]
Africa
Burkinabe 75% [15]
Gambia 65e85% [13]
Ghana 68% [13]
Asia
China 50e80% [12,16]
Vietnam 70% [17]
Philippines 46% [12]
Taiwan 83e100% [18e20]
Table 3 Functions of HMOs.
Prebiotics effect
Antiadhesive antimicrobials
Immune modulators
Modulators of intestinal cell response
Neurodevelopment and cognition
Y.-J. Cheng and C.-Y. Yeung
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4
mother’s milk may become a non-invasive biomarker to
identify breast-fed infants at risk of developing NEC.
56,58
Further studies are needed to validate the association
between DSLNT and reduced NEC risk.
5. Clinical trials and safety issues
In 2015, Marriage et al. published the first randomized
control trial comparing the safety and clinical implication
of human milk and formula supplemented with one HMO-
20-fucosyllactose (20FL).
59
In this study, formula-fed in-
fants were randomized to 1 of 3 formulas containing gal-
actooligosaccharides (GOS), and the two experimental
formulas contained varying levels (0.2 and 1.0 g/L) of HMO
20FL. Growth parameters including weight, length and
head circumference showed no differences between in-
fants fed human milk or experimental formula during the
4-month study period. Also, the formula containing GOS
and HMOs were well-tolerated without report of signifi-
cant adverse effects. The relative absorption and excre-
tion of 20FL of formula-fed infants decreased gradually,
which was similar to those infants fed human milk.
Another randomized controlled study also tested the
gastrointestinal tolerance of a formula supplied with 20FL
(0.2 g/L) and short-chain fructooligosaccharides (scFOS).
60
Similarly, the experimental formula was well-tolerated
without differences in stool consistency, anthropometric
data and frequency of feedings with spitting up/vomiting
compared to infants fed without oligosaccharides and
breast-fed infants.
In 2017, Puccio et al. conducted the first clinical trial
evaluating infant formula supplemented with 2 HMOs (2-FL
and LNnT).
61
When compared to infants fed control formula
without HMOs, infants fed test formula presented similar
age-appropriate growth, improvement of colic in the first
few months and they had lower parental reports of lower
respiratory tract infections as well as antipyretic and
antibiotic use. The immune function of HMOs was further
investigated in a subgroup analysis of the above study.
62
Breastfed infants and infants fed formula with 20FL and
GOS had 29e83% lower concentrations of plasma inflam-
matory cytokines and tumor necrosis factor-a(TNF-a) than
infants fed the control formula with GOS only. The results
suggest that HMOs support aspects of immune development
and regulation similar to that of breastfed infants.
The US Food and Drug Administration (FDA) and the
European Food Safety Authority (EFSA) approved the safety
of 20FL and LNnT, respectively, as ingredients in infant
formula.
63
To date, 20FL has been added to commercial
infant formula with advances of bioengineering and pro-
duction. However, further studies are still needed to assess
pros and cons of adding individual HMOs in milk formula as
compared with human milk.
6. Summary
Breast feeding and human milk are the standards for infant
feeding and nutrition. HMOs are one of the major differ-
ences between human milk and formula milk. Currently
available evidence demonstrates their various beneficial
effects toward infants’ health. HMOs serve as decoy
receptors that prevent the attachment of pathogens to
epithelial cells to protect against infectious disease. HMOs
modulate host intestinal epithelial and immune cell re-
sponses. Breast milk feeding remains the best option for
infants nutrition and development. However, when breast
milk is not adequate or available, infant formula supple-
mented with HMOs may be considered as an alternative.
Declaration of competing interest
The authors did not receive any financial or non-financial
benefits from any commercial entity in support of this
article.
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... In fact, in 2015 the European Food Safety Authority (EFSA) approved the use of 2 0 fucosyllactose (2 0 FL) and LNnT as novel food ingredients to add to infant formula. Likewise, the US Food and Drug administration approved the safety of these two HMOs (in 2016) and 3 0 -FL (in 2019) as ingredients to add to infant and follow-on formula (Vandenplas et al., 2018;Cheng and Yeung., 2021;Moubareck, 2021). ...
... Different studies on metabolism of HMOs have shown that they resist the digestion and reach the colon where they stimulate the development of several bifidobacteria of the infant gut microbiota, being considered as the first prebiotics for humans (Coppa et al., 2006;Kong et al., 2020). There is considerable scientific evidence indicating beneficial effects of HMOs as participation in the shaping of intestinal gut microbiome, gut development, anti-inflammatory modulation of intestinal epithelial cell response, effects on immune maturation of infant indirectly avoiding dysbiosis in the intestine, and brain development (Thomson et al., 2018;Vandenplas et al., 2018;Chouraqui, 2020;Al-Khafajia et al., 2020;Cheng and Yeung, 2021). Some HMOs modulate epithelial and immune cell responses reducing excessive mucosal leukocyte infiltration and activation protecting against the necrotizing enterocolitis (NEC), a disease that commonly affects very premature infants. ...
... Some HMOs modulate epithelial and immune cell responses reducing excessive mucosal leukocyte infiltration and activation protecting against the necrotizing enterocolitis (NEC), a disease that commonly affects very premature infants. Indeed, the probability of suffering NEC in preterm infants fed exclusively with human milk has been reduced by 6 to 10 times compared to formula-fed infants (Chen, 2015;Cheng and Yeung, 2021). ...
Chapter
Human gut microbiota (HGM) is a complex functional ecosystem with different biological functions and any alteration in its composition can affect different aspects of human health. Diet is an external factor that can affect the HGM composition and metabolic functions therefore the consumption of specific food ingredients ensures the incorporation of substrates for fermentation by intestinal bacteria. Here, we review the pathways of metabolism of dietary carbohydrates including dietary fiber, selected prebiotics and human milk oligosaccharides (HMOs) by gut microbiota. Metabolites originated by intestinal microbiota fermentation and their beneficial effects for the host health have been widely described.
... The HMO concentration in the lactating mother is higher during the early stages and gradually decreases over time [74][75][76]. Structurally, HMO are composed of five monosaccharides: glucose, galactose, N-acetylglucosamine, fucose, and N-acetylneuraminic acid or sialic acid [77][78][79]. They are synthesized from a lactose core (galactose-β (1→4) glucose) by glycosyl transferases in the lactocyte. ...
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Diabetes and obesity are metabolic diseases that have become alarming conditions in recent decades. Their rate of increase is becoming a growing concern worldwide. Recent studies have established that the composition and dysfunction of the gut microbiota are associated with the development of diabetes. For this reason, strategies such as the use of prebiotics to improve intestinal microbial structure and function have become popular. Consumption of prebiotics for modulating the gut microbiota results in the production of microbial metabolites such as short-chain fatty acids that play essential roles in reducing blood glucose levels, mitigating insulin resistance, reducing inflammation, and promoting the secretion of glucagon-like peptide 1 in the host, and this accounts for the observed remission of metabolic diseases. Prebiotics can be either naturally extracted from non-digestible carbohydrate materials or synthetically produced. In this review, we discussed current findings on how the gut microbiota and microbial metabolites may influence host metabolism to promote health. We provided evidence from various studies that show the ability of prebiotic consumption to alter gut microbial profile, improve gut microbial metabolism and functions, and improve host physiology to alleviate diabetes and obesity. We conclude among other things that the application of systems biology coupled with bioinformatics could be essential in ascertaining the exact mechanisms behind the prebiotic–gut microbe–host interactions required for diabetes and obesity improvement.
... The HMO concentration in the lactating mother is higher during the early stages and gradually decreases over time [74][75][76]. Structurally, HMO are composed of five monosaccharides: glucose, galactose, N-acetylglucosamine, fucose, and N-acetylneuraminic acid or sialic acid [77][78][79]. They are synthesized from a lactose core (galactose-β (1→4) glucose) by glycosyl transferases in the lactocyte. ...
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Diabetes and obesity are metabolic diseases that have become alarming conditions in recent decades. Their rate of increase is becoming a growing concern worldwide. Recent studies have established that the composition and dysfunction of the gut microbiota are associated with the development of diabetes. For this reason, strategies such as the use of prebiotics to improve intestinal microbial structure and function have become popular. Consumption of prebiotics for modulating the gut microbiota results in the production of microbial metabolites such as short-chain fatty acids that play essential roles in reducing blood glucose levels, mitigating insulin resistance, reducing inflammation, and promoting the secretion of glucagon-like peptide 1 in the host, and this accounts for the observed remission of metabolic diseases. Prebiotics can be either naturally extracted from non-digestible carbohydrate materials or synthetically produced. In this review, we discussed current findings on how the gut microbiota and microbial metabolites may influence host metabolism to promote health. We provided evidence from various studies that show the ability of prebiotic consumption to alter gut microbial profile, improve gut microbial metabolism and functions, and improve host physiology to alleviate diabetes and obesity. We conclude among other things that the application of systems biology coupled with bioinformatics could be essential in ascertaining the exact mechanisms behind the prebiotic-gut microbe-host interactions required for diabetes and obesity improvement.
... HM contains immunoglobulins, growth peptides, and over 200 types of human milk oligosaccharides (HMOs). HMOs act as prebiotics and promote the growth of beneficial bacteria while blocking pathogens from binding to epithelial cells (Cheng and Yeung 2021;Wiciński et al. 2020). This translates into prevention of gastrointestinal and respiratory tract infections (Andreas, Kampmann, and Mehring Le-Doare 2015). ...
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The primary aim of this review was to systematically evaluate the literature regarding the effect of pre-, pro-, or synbiotic supplementation in infant formula on the gastrointestinal microbiota. The Cochrane methodology for systematic reviews of randomized controlled trials (RCTs) was employed. Five databases were searched and 32 RCTs (2010–2021) were identified for inclusion: 20 prebiotic, 6 probiotic, and 6 synbiotic. The methods utilized to evaluate gastrointestinal microbiota varied across studies and included colony plating, fluorescence in situ hybridization, quantitative real-time polymerase chain reaction, or tagged sequencing of the 16S rRNA gene. Fecal Bifidobacterium levels increased with supplementation of prebiotics and synbiotics but not with probiotics alone. Probiotic and synbiotic supplementation generally increased fecal levels of the bacterial strain supplemented in the formula. Across all pre-, pro-, and synbiotic-supplemented formulas, results were inconsistent regarding fecal Clostridium levels. Fecal pH was lower with some prebiotic and synbiotic supplementation; however, no difference was seen with probiotics. Softer stools were often reported in infants supplemented with pre- and synbiotics, yet results were inconsistent for probiotic-supplemented formula. Limited evidence demonstrates that pre- and synbiotic supplementation increases fecal Bifidobacterium levels. Future studies utilizing comprehensive methodologies and additional studies in probiotics and synbiotics are warranted.
... 59,60 The studies in infants revealed that they offer protection against infectious diarrhea, necrotizing enterocolitis, and can directly inhibit the growth of group B streptococcus (GBS), a leading cause of invasive bacterial infection in newborns. [61][62][63][64] Moreover, HMOs are suggested to potentiate the actions of aminoglycosides, anti-folates, macrolides, lincosamides, and tetracyclines against GBS, S. aureus and A. baumannii. 57,65 Hence, prophylactic and therapeutic use of HMOs is also possible in immune compromised infants as well as in those at high risk of infection. ...
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This review by pediatric gastroenterology and allergy-immunology experts aimed to address the biological roles of human milk oligosaccharides (HMOs) and the potential utility of HMOs in prevention of allergy with particular emphasis on cow's milk protein allergy (CMPA). The participating experts consider HMOs amongst the most critical bioactive components of human milk, which act as antimicrobials and antivirals by preventing pathogen adhesion to epithelial cells, as intestinal epithelial cell modulators by enhancing maturation of intestinal mucosa and intestinal epithelial barrier function, as prebiotics by promoting healthy microbiota composition and as immunomodulators by modulating immune cells indirectly and directly. Accordingly, the participating experts consider the proposed link between HMOs and prevention of allergy to be primarily based on the impact of HMO on gut microbiota, intestinal mucosal barrier, immunomodulation and immune maturation. Along with the lower risk of respiratory and gastrointestinal infections, HMO-supplemented formulas seem to be promising alternatives in the management of CMPA. Nonetheless, the effects of individual as well as complex mixtures of HMO in terms of clear clinical and immunological effects and tolerance development need to be further explored to fully realize the immunomodulatory mechanisms and the potential for HMOs in prevention of allergic diseases and CMPA.
... The first opportunity is promoting a healthier diet in pregnant women, in whom high consumption of fruits and vegetables can positively influence the newborn microbiome [248]. Moreover, infant formula supplementation with prebiotics such as oligosaccharides can increase the growth of Bifidobacterium (a known SCFA producer) and reduce inflammatory cytokines compared with babies fed with the non-supplemented formula [249]. Additionally, infant formula supplementation with PAs promotes the growth of Bacteroides, Prevotella and Lactobacillus on neonatal BALB/cOlaHsd mice [250]. ...
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The microbiota regulates immunological development during early human life, with long- term effects on health and disease. Microbial products include short-chain fatty acids (SCFAs), formyl peptides (FPs), polysaccharide A (PSA), polyamines (PAs), sphingolipids (SLPs) and aryl hydrocarbon receptor (AhR) ligands. Anti-inflammatory SCFAs are produced by Actinobacteria, Bacteroidetes, Firmicutes, Spirochaetes and Verrucomicrobia by undigested-carbohydrate fermentation. Thus, fiber amount and type determine their occurrence. FPs bind receptors from the pattern recognition family, those from commensal bacteria induce a different response than those from pathogens. PSA is a capsular polysaccharide from B. fragilis stimulating immunoregulatory protein expression, promoting IL-2, STAT1 and STAT4 gene expression, affecting cytokine production and response modulation. PAs interact with neonatal immunity, contribute to gut maturation, modulate the gut– brain axis and regulate host immunity. SLPs are composed of a sphingoid attached to a fatty acid. Prokaryotic SLPs are mostly found in anaerobes. SLPs are involved in proliferation, apoptosis and immune regulation as signaling molecules. The AhR is a transcription factor regulating development, reproduction and metabolism. AhR binds many ligands due to its promiscuous binding site. It participates in immune tolerance, involving lymphocytes and antigen-presenting cells during early development in exposed humans.
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Microbial synthesis of 2'-fucosyllactose (2'-FL) has received much attention in recent years. In this study, Bacillus subtilis ATCC 6051a, a nonpathogenic GRAS (generally recognized as safe) organism, was engineered to produce 2'-FL. After a synthetic pathway comprising six genes was incorporated into the host cell genome, only a low level of 2'-FL (120 mg/L) was initially detected in recombinant cell culture. Comparison of heterologous lactose transporters confirmed the superior role of LacY from Escherichia coli for efficient production of 2'-FL in B. subtilis. There are two β-galactosidases, GanA and YesZ, in B. subtilis. Deletion of ganA and yesZ caused by insertion of the lacY cassette led to 2'-FL accumulation in shaking-flask culture at concentrations of 3.13 g/L and 5.56 g/L, respectively, which increased to 6.13 g/L in the double-deletion strain 164FL-GY. In addition, enhanced xylose metabolism in 164FL-GY further increased the concentration of 2'-FL to 7.14 g/L. In fed-batch fermentation, the highest productivity of 0.56 g/L·h was achieved in glycerol and xylose containing medium using engineered B. subtilis, and the accumulated 2'-FL reached 31.2 g/L. This is the first report of recombinant B. subtilis for high-level production of 2'-FL via a de novo synthesis pathway.
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Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a global health crisis with more than four million deaths worldwide. A substantial number of COVID-19 survivors continue suffering from long-COVID syndrome, a long-term complication exhibiting chronic inflammation and gut dysbiosis. Much effort is being expended to improve therapeutic outcomes. Human milk oligosaccharides (hMOS) are non-digestible carbohydrates known to exert health benefits in breastfed infants by preventing infection, maintaining immune homeostasis and nurturing healthy gut microbiota. These beneficial effects suggest the hypothesis that hMOS might have applications in COVID-19 as receptor decoys, immunomodulators, mucosal signaling agents, and prebiotics. This review summarizes hMOS biogenesis and classification, describes the possible mechanisms of action of hMOS upon different phases of SARS-CoV-2 infection, and discusses the challenges and opportunities of hMOS research for clinical applications in COVID-19.
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The intestinal microbiota begins to take shape in the mother’s womb, changes depending on many factors. It is known that the intestinal microbiota has an important role in the maturation of the immune system, also in the prevention of diseases that occur in newborn, childhood, adulthood. Nutrition is the main factor on the development of microbiota in infants after birth. The microbiota compositions of breastfed infants are different from formula-fed infants. Breast milk oligosaccharides play an important role in the development of infants’ microbiota. The higher number of Bifidobacterium species and lower α and β diversity in breastfed infants are considered protective. A dysbiosis occurring in the microbiota can cause adverse effects on health. Human milk oligosaccharides also have protective effects on the microbiota. These protective effects are to promote the growth of intestinal microbiota, prevent the adhesion of viruses to the colon, promote the growth of Bifidobacterium with its prebiotic effect. Short-chain fatty acids resulting from their digestion, also have protective effects. Another component that shapes the gut microbiota is HM glycoproteins. The aim of this study is to examine the effect of breast milk on the development of microbiota, to present the results by scanning the literature.
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Breast milk is the optimal food choice for infant growth and development. Among breast milk components, fructooligosaccharides (FOSs) are being actively studied because of their role in microbiota development. In particular, 2'-fucosyllactose is being proposed as a potential supplement/nutraceutical or component of infant formula. In this systematic review, we critically summarize the available information on FOSs and we discuss their future use in infant nutrition. We searched the main electronic databases (PubMed, Embase, and Scopus), with a final check in May 2021. Search terms were inserted individually and using the Boolean tools AND and OR. Relevant articles were identified using the following words: ("fructooligosaccharides" OR "FOS") AND ("human milk" OR "breast milk" OR "donor milk" OR "bank milk"). The search retrieved 1814 articles. After removal of duplicates, we screened 1591 articles based on title, abstract, and exclusive use of the English language. We included articles describing the concentration of FOSs in human milk and assessed the relevant ones. We excluded reviews, studies on animals, and studies exclusively carried out on adults. Also, we excluded studies that have not reported evidence either on FOSs or on galactooligosaccharides from human milk. The resulting publications were reviewed, and 10 studies were included in the systematic review. We conclude that human milk FOSs are, indeed, crucial to infant gut development and their addition to infant formula is safe, well-tolerated, and might provide immune benefits to newborns. However, we would like to underscore the scantiness of human data and the need to avoid the immediate translation of infant research to the commercialization of supplements marketed to adults.
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Background Infant cognitive development is influenced by maternal factors that range from obesity to early feeding and breast milk composition. Animal studies suggest a role for human milk oligosaccharide (HMO), 2’-fucosyllactose (2’FL), on learning and memory, yet no human studies have examined its impact on infant cognitive development relative to other HMOs and maternal factors. Objective To determine the impact of 2’FL from breast milk feeding on infant cognitive development at 24 months of age relative to maternal obesity and breast milk feeding frequency. Methods and materials Hispanic mother-infant pairs (N = 50) were recruited across the spectrum of pre-pregnancy BMI. Breast milk was collected at 1 and 6 months, and feedings/day were reported. Nineteen HMOs were analyzed using high-performance liquid chromatography, with initial interest in 2’FL. Infant cognitive development score was assessed with the Bayley-III Scale at 24 months. Linear regressions were used for prediction, and bootstrapping to determine mediation by 2’FL. Results Maternal pre-pregnancy BMI was not related to feedings/day or HMOs, but predicted poorer infant cognitive development (β = -0.31, P = 0.03). Feedings/day (β = 0.34) and 2’FL (β = 0.59) at 1 month predicted better infant cognitive development (both P≤ 0.01). The association of feedings/day with infant cognitive development was no longer significant after further adjustment for 2’FL (estimated mediation effect = 0.13, P = 0.04). There were no associations of feedings/day and 2’FL at 6 months with infant cognitive development. Conclusions Our findings suggest that maternal factors influence infant cognitive development through multiple means. Though maternal obesity may be a separate negative influence, greater frequency of breast milk feeding at 1 month contributed to infant cognitive development through greater exposure to 2’FL relative to other HMOs. The influence of 2’FL was not significant at 6 months, indicating that early exposure to 2’FL may be a critical temporal window for positively influencing infant cognitive development.
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Abstract Breastfeeding is the normal way of providing young infants with the nutrients they need for healthy growth and development (WHO). Human milk oligosaccharides (hMOS) constitute a highly important class of nutrients that are attracting strong attention in recent years. Several studies have indicated that hMOS have prebiotic properties, but also are effective in anti-adhesion of pathogens, modulating the immune system and providing nutrients for brain growth and development. Most of the latter functions seem to be linked to the presence of fucose-containing immunodeterminant epitopes, and Neu5Ac-bearing oligosaccharides. Analysis of hMOS isolated from 101 mothers’ milk showed regional variation in Lewis- and Secretor based immunodeterminants. Lewis-negative milk groups could be sub-divided into two sub-groups, based on the activity of a third and hitherto unidentified fucosyltransferase enzyme. Analysis of hMOS remaining in faeces showed three sub-groups based on hMOS surviving passage through the gut, full consumption, specific partial consumption and non-specific partial consumption, fitting previous findings.
Article
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To study the variability in human milk oligosaccharide (HMO) composition of Chinese human milk over a 20-wk lactation period, HMO profiles of 30 mothers were analyzed using CE-LIF. This study showed that total HMO concentrations in Chinese human milk decreased significantly over a 20-wk lactation period, independent of the mother’s SeLe status, although with individual variations. In addition, total acidic and neutral HMO concentrations in Chinese human milk decreased over lactation, and levels are driven by their mother’s SeLe status. Analysis showed that total neutral fucosylated HMO concentrations in Chinese human milk were higher in the two secretor groups compared to the non-secretor group. Based on the total neutral fucosylated HMO concentrations in Chinese human milk, HMO profiles within the Se+Le+ group can be divided in 2 subgroups. HMOs that differed in level between Se+Le+ subgroups were 2’FL, DF-L, LNFP I, and F-LNO. HMO profiles in Dutch human milk also showed Se+Le+ subgroup division, with 2’FL, LNT, and F-LNO as driving force.
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In December 2016, a panel of experts in microbiology, nutrition and clinical research was convened by the International Scientific Association for Probiotics and Prebiotics to review the definition and scope of prebiotics. Consistent with the original embodiment of prebiotics, but aware of the latest scientific and clinical developments, the panel updated the definition of a prebiotic: a substrate that is selectively utilized by host microorganisms conferring a health benefit. This definition expands the concept of prebiotics to possibly include non-carbohydrate substances, applications to body sites other than the gastrointestinal tract, and diverse categories other than food. The requirement for selective microbiota-mediated mechanisms was retained. Beneficial health effects must be documented for a substance to be considered a prebiotic. The consensus definition applies also to prebiotics for use by animals, in which microbiota-focused strategies to maintain health and prevent disease is as relevant as for humans. Ultimately, the goal of this Consensus Statement is to engender appropriate use of the term 'prebiotic' by relevant stakeholders so that consistency and clarity can be achieved in research reports, product marketing and regulatory oversight of the category. To this end, we have reviewed several aspects of prebiotic science including its development, health benefits and legislation.
Article
Background: When sufficient maternal breast milk is not available, alternative forms of enteral nutrition for preterm or low birth weight (LBW) infants are donor breast milk or artificial formula. Donor breast milk may retain some of the non-nutritive benefits of maternal breast milk for preterm or LBW infants. However, feeding with artificial formula may ensure more consistent delivery of greater amounts of nutrients. Uncertainty exists about the balance of risks and benefits of feeding formula versus donor breast milk for preterm or LBW infants. Objectives: To determine the effect of feeding with formula compared with donor breast milk on growth and development in preterm or low birth weight (LBW) infants. Search methods: We used the Cochrane Neonatal search strategy, including electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 5), Ovid MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (3 May 2019), as well as conference proceedings, previous reviews, and clinical trials. Selection criteria: Randomised or quasi-randomised controlled trials (RCTs) comparing feeding with formula versus donor breast milk in preterm or LBW infants. Data collection and analysis: Two review authors assessed trial eligibility and risk of bias and extracted data independently. We analysed treatment effects as described in the individual trials and reported risk ratios (RRs) and risk differences (RDs) for dichotomous data, and mean differences (MDs) for continuous data, with respective 95% confidence intervals (CIs). We used a fixed-effect model in meta-analyses and explored potential causes of heterogeneity in subgroup analyses. We assessed the certainty of evidence for the main comparison at the outcome level using GRADE methods. Main results: Twelve trials with a total of 1879 infants fulfilled the inclusion criteria. Four trials compared standard term formula versus donor breast milk and eight compared nutrient-enriched preterm formula versus donor breast milk. Only the five most recent trials used nutrient-fortified donor breast milk. The trials contain various weaknesses in methodological quality, specifically concerns about allocation concealment in four trials and lack of blinding in most of the trials. Most of the included trials were funded by companies that made the study formula.Formula-fed infants had higher in-hospital rates of weight gain (mean difference (MD) 2.51, 95% confidence interval (CI) 1.93 to 3.08 g/kg/day), linear growth (MD 1.21, 95% CI 0.77 to 1.65 mm/week) and head growth (MD 0.85, 95% CI 0.47 to 1.23 mm/week). These meta-analyses contained high levels of heterogeneity. We did not find evidence of an effect on long-term growth or neurodevelopment. Formula feeding increased the risk of necrotising enterocolitis (typical risk ratio (RR) 1.87, 95% CI 1.23 to 2.85; risk difference (RD) 0.03, 95% CI 0.01 to 0.05; number needed to treat for an additional harmful outcome (NNTH) 33, 95% CI 20 to 100; 9 studies, 1675 infants).The GRADE certainty of evidence was moderate for rates of weight gain, linear growth, and head growth (downgraded for high levels of heterogeneity) and was moderate for neurodevelopmental disability, all-cause mortality, and necrotising enterocolitis (downgraded for imprecision). Authors' conclusions: In preterm and LBW infants, moderate-certainty evidence indicates that feeding with formula compared with donor breast milk, either as a supplement to maternal expressed breast milk or as a sole diet, results in higher rates of weight gain, linear growth, and head growth and a higher risk of developing necrotising enterocolitis. The trial data do not show an effect on all-cause mortality, or on long-term growth or neurodevelopment.
Article
Background and objectives: Breast milk contains several bioactive factors including human milk oligosaccharides (HMOs) and microbes that shape the infant gut microbiota. HMO profile is determined by secretor status; however, their influence on milk microbiota is still uncovered. This study is aimed to determine the impact of the FUT2 genotype on the milk microbiota during the first month of lactation and the association with HMO. Methods: Milk microbiota from 25 healthy lactating women was determined by quantitative polymerase chain reaction and 16S gene pyrosequencing. Secretor genotype was obtained by polymerase chain reaction-random fragment length polymorphisms and by HMO identification and quantification. Results: The most abundant bacteria were Staphylococcus and Streptococcus, followed by Enterobacteriaceae-related bacteria. The predominant HMO in secretor milk samples were 2'FL and lacto-N-fucopentaose I, whereas non-secretor milk was characterized by lacto-N-fucopentaose II and lacto-N-difucohexaose II. Differences in microbiota composition and quantity were found depending on secretor/non-secretor status. Lactobacillus spp, Enterococcus spp, and Streptococcus spp were lower in non-secretor than in secretor samples. Bifidobacterium genus and species were less prevalent in non-secretor samples. Despite no differences on diversity and richness, non-secretor samples had lower Actinobacteria and higher relative abundance of Enterobacteriaceae, Lactobacillaceae, and Staphylococcaceae. Conclusions: Maternal secretor status is associated with the human milk microbiota composition and is maintained during the first 4 weeks. Specific associations between milk microbiota, HMO, and secretor status were observed, although the potential biological impact on the neonate remains elusive. Future studies are needed to reveal the early nutrition influence on the reduction of risk of disease.
Article
Background: When sufficient maternal breast milk is not available, alternative forms of enteral nutrition for preterm or low birth weight (LBW) infants are donor breast milk or artificial formula. Donor breast milk may retain some of the non-nutritive benefits of maternal breast milk for preterm or LBW infants. However, feeding with artificial formula may ensure more consistent delivery of greater amounts of nutrients. Uncertainty exists about the balance of risks and benefits of feeding formula versus donor breast milk for preterm or LBW infants. Objectives: To determine the effect of feeding with formula compared with donor breast milk on growth and development in preterm or low birth weight (LBW) infants. Search methods: We used the Cochrane Neonatal search strategy, including electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 6), Ovid MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature (until 8 June 2017), as well as conference proceedings and previous reviews. Selection criteria: Randomised or quasi-randomised controlled trials (RCTs) comparing feeding with formula versus donor breast milk in preterm or LBW infants. Data collection and analysis: Two review authors assessed trial eligibility and risk of bias and extracted data independently. We analysed treatment effects as described in the individual trials and reported risk ratios (RRs) and risk differences (RDs) for dichotomous data, and mean differences (MDs) for continuous data, with respective 95% confidence intervals (CIs). We used a fixed-effect model in meta-analyses and explored potential causes of heterogeneity in subgroup analyses. We assessed the quality of evidence for the main comparison at the outcome level using "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) methods. Main results: Eleven trials, in which 1809 infants participated in total, fulfilled the inclusion criteria. Four trials compared standard term formula versus donor breast milk and seven compared nutrient-enriched preterm formula versus donor breast milk. Only the four most recent trials used nutrient-fortified donor breast milk. The trials contain various weaknesses in methodological quality, specifically concerns about allocation concealment in four trials and lack of blinding in most of the trials.Formula-fed infants had higher in-hospital rates of weight gain (mean difference (MD) 2.51, 95% confidence interval (CI) 1.93 to 3.08 g/kg/day), linear growth (MD 1.21, 95% CI 0.77 to 1.65 mm/week) and head growth (MD 0.85, 95% CI 0.47 to 1.23 mm/week). We did not find evidence of an effect on long-term growth or neurodevelopment. Formula feeding increased the risk of necrotising enterocolitis (typical risk ratio (RR) 1.87, 95% CI 1.23 to 2.85; risk difference (RD) 0.03, 95% CI 0.01 to 0.06).The GRADE quality of evidence was moderate for rates of weight gain, linear growth, and head growth (downgraded for high levels of heterogeneity) and was moderate for neurodevelopmental disability, all-cause mortality, and necrotising enterocolitis (downgraded for imprecision). Authors' conclusions: In preterm and LBW infants, feeding with formula compared with donor breast milk, either as a supplement to maternal expressed breast milk or as a sole diet, results in higher rates of weight gain, linear growth, and head growth and a higher risk of developing necrotising enterocolitis. The trial data do not show an effect on all-cause mortality, or on long-term growth or neurodevelopment.
Article
Necrotizing enterocolitis (NEC) is one of the most common and devastating intestinal disorders in preterm infants. Therapies to meet the clinical needs for this special and highly vulnerable population are extremely limited. A specific human milk oligosaccharide (HMO), disialyllacto-N-tetraose (DSLNT), was shown to contribute to the beneficial effects of breastfeeding as it prevented NEC in a neonatal rat model and was associated with lower NEC risk in a human clinical cohort study. Herein, gram-scale synthesis of two DSLNT analogs previously shown to have NEC preventing effect is described. In addition, four novel disialyl glycans have been designed and synthesized by enzymatic or chemoenzymatic methods. Noticeably, two disialyl tetraoses have been produced by enzymatic sialylation of chemically synthesized thioethyl β-disaccharides followed by removal of the thioethyl aglycon. Dose-dependent and single-dose comparison studies showed varying NEC-preventing effects of the disialyl glycans in neonatal rats. This study helps to refine the structure requirement of the NEC-preventing effect of disialyl glycans and provides important dose-dependent information for using DSLNT analogs as potential therapeutics for NEC prevention in preterm infants.
Article
Objectives: Human milk oligosaccharides (HMOs) are known as important factors in neurologic and immunologic development of neonates. Moreover, freeze-drying seems to be a promising storage method to improve the processes of human milk banks. However, the effects of pasteurization and freeze-drying on HMOs were not evaluated yet. The purpose of this study is to analyze and compare the HMOs profiles of human milk collected before and after the pasteurization and freeze-drying. Methods: Totally nine fresh human milk samples were collected from three healthy mothers at the first, second, and third week after delivery. The samples were treated with Holder pasteurization and freeze-drying. HMOs profiles were analyzed by matrix-assisted laser desorption/ionization (MALDI) time-of-flight/time-of-flight (TOF/TOF) mass spectrometry and compared between samples collected before and after the treatments. Results: Human milk samples showed significantly different HMO patterns between mothers. However, HMOs were not affected by lactation periods within 3 weeks after delivery (r² = 0.972–0.999, p < .001). Moreover, both of pasteurization and freeze-drying were found not to affect HMO patterns in a correlation analysis (r² = 0.989–0.999, p < .001). Conclusion: HMO patterns were found not to be affected by pasteurization and freeze-drying of donor milks. We hope that introducing freeze-drying to the human milk banks would be encouraged by the present study. However, the storage length without composition changes of HMOs after freeze-drying needs to be evaluated in the further studies.
Article
The salivary ABH and Lewis antigens of Polynesians were measured using a standardised red cell agglutination microplate assay and compared with the red cell defined Lewis phenotypes. Salivary ABH substances were detected in almost all saliva samples tested, with low levels (partial secretion) of ABH substances in the saliva from Le(a+b-) and Le(a+b+) individuals. Salivary Le^b substance was detected in all Le(a-b+) and Le(a+b+) samples and in almost all Le(a+b-) samples. It is evident from the results obtained that Polynesian red cell phenotypes cannot be used to predict the presence or absence of salivary substances. If the presence of a coding secretor gene is presumed responsible for salivary ABH antigens and salivary Le^b antigen expression, then the incidence of a coding secretor gene in Polynesians is 98%. These results indicate that the recessive non-secretor gene is absent or rare in a Polynesian derived gene pool. Two variants of secretor individuals are found among Polynesians, secretors with expression of normal amounts of the product of the secretor gene, similar to Caucasians, and partial secretors with weak expression of the secretor gene products.