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Arabinoxylan structural characteristics, interaction with gut microbiota and

potential health functions

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DOI: 10.1016/j.jff.2019.02.007

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 Journal of Functional Foods 54 (2019) 536–551

Contents lists available at ScienceDirect

Journal of Functional Foods

journal homepage: www.elsevier.com/locate/jff

Arabinoxylan structural characteristics, interaction with gut microbiota and T

potential health functions
⁎
Zhuoyun Chena,1, Shanshan Lia,1, Yuanfang Fua, Cheng Lia, Daiwen Chenb, Hong Chena,
a
College of Food Science, Sichuan Agricultural University, Ya’an, Sichuan 625014, China
b
Institute of Animal Nutrition, Sichuan Agricultural University, Postcode 611130, Chengdu, Sichuan, China

A R T I C LE I N FO A B S T R A C T

Keywords: Arabinoxylans are the main type of noncellulose polysaccharide in cereals and grasses. They are also important
Dietary fiber functional ingredients in baked products. Arabinoxylans derived from different sources or extracted in different
Physiological functions ways may exhibit different structures which give rise to various physiological functions and exert diverse im-
Structural features pacts on gut microbiota. This review summarizes the most current researches on arabinoxylans’ beneficial effects
Fermentation
to human health, their prebiotic effects, the influences of structural features on short-chain fatty acids pro-
Prebiotic effects
Antioxidant effect
duction as well as on physiological functions. We aim to identify arabinoxylans’ primary structural features that
related to each functional property and also provide the explaination to the inconsistent antioxidant capacity of
arabinoxylans with similar structural features.

1. Introduction
Arabinoxylans (AXs) are the main kind of hemicelluloses in many
cereal grains. They are mostly originated from the bran and starchy
endosperm, and can’t be degraded by mammalian enzymes (Fadel et al.,
2017; Zhou et al., 2010). AXs demonstrate many functional properties
in food production and physiological processes during metabolism. For
instance, they can strengthen the immune system (Biliaderis &
Izydorczyk, 2007; Glitso, Jensen, & Bach Knudsen, 2000; Izydorczyk &
Dexter, 2008; Qiang, Chao, & Wan, 2009), lower the possibility of the
occurrence of diseases (e.g. cardiovascular diseases, diabetes type 2,
obesity and colon cancer), decrease the organ damage especially for
liver as well as promote the number of probiotic bacteria growing in gut
(Biliaderis & Izydorczyk, 2007; Chen et al., 2018). It is believed that the
change of intestinal microbiota stimulated by AXs improves minerals
absorption and resists the invasion of pathogen in the gut (Broekaert
et al., 2011).
AXs can be derived from a wide range of sources including cereals
such as maize, rye, barley, oats, sorghum, wheat, rice, and other plants
such as banana. Likewise, varieties of extraction methods have been
studied to produce AXs, for example, water, alkaline, enzyme extrac-
tions, and physical treatments and various combination of the
techniques (Fadel et al., 2017; Fry, 2004; Izydorczyk & Biliaderis, 1995;
Yadav, Kale, Hicks, & Hanah, 2017). The structures of AXs, however,
originated from different raw materials or extracted by different
methods are not highly consistent. Each may has different unique
structural features (different sugar composition, molecular weight
(MW), type of branching, binding, etc.). For instance, compared with
AXs from barley, AXs from banana peel hemicellulose or from corn hull
contain higher galactose or glucuronic acid while enzymatic treatment
produced AXs have lower molecule weight and with higher ferulic acid
(FA) content than alkali treated ones (Ogawa, Takeuchi, & Nakamura,
2005; Samuelsen, Rieder, Grimmer, Michaelsen, & Knutsen, 2011; Zhou
et al., 2010).
Lots of studies have shown that AXs with different structural fea-
tures exhibit different biological activities. There is a strong correlation
between molecule structure and physiological functions for AXs (Ayala-
Soto, Serna-Saldívar, Welti-Chanes, & Gutierrez-Uribe, 2015; Gemen,
de Vries, & Slavin, 2011; Geraylou et al., 2013; Malunga, Izydorczyk, &
Beta, 2017; Mendis, Leclerc, & Simsek, 2016; Sarma et al., 2018; Zhang,
Li, Smith, & Musa, 2015). The aim of this article is to summarize the
health benefits of AXs occurred in the physiological processes. Because
some of the health benefits are related to gut microbiota, we also sum
up the interaction between AXs and gut microbiota. In the meantime,

Abbreviations: AXs, arabinoxylans; MW, molecular weight; FA, ferulic acid; DP, degree of polymerization; DS, degree of substitution; AXOS, arabinox-
ylooligosaccharides; SCFAs, short chain fatty acids; PUL, polysaccharide utilization loci; Sus, starch utilization system; LDL, low-density lipoprotein; BA, bile acids;
GLP-1, glucagon-like peptide 1; GLP-2, glucagon-like peptide 2; Igs, immunoglobulins; WEAX, water extractable AXs
⁎
Corresponding author.
E-mail address: chenhong945@sicau.edu.cn (H. Chen).
1
Zhuoyun Chen and Shanshan Li contributed equally to this article.

https://doi.org/10.1016/j.jff.2019.02.007
Received 27 October 2018; Received in revised form 4 February 2019; Accepted 4 February 2019
1756-4646/ © 2019 Elsevier Ltd. All rights reserved.
Z. Chen et al.
Xyl - Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl –Xyl – Xyl – Xyl
2 3
1 1
β-L-Ara 1 3 α-L-Ara 1 3α-L-Ara Ara
5 Glca
O
Gal Glu
1 1
2 2
Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl –Xyl – Xyl – Xyl – Xyl
2 2
1 1
Gal – Ara
Xyl – Ara
Fig. 1. The schematic diagram of AX main structural characteristics. The structure of AX can vary and are related to the raw materials or extraction methods (Zhang,
Li, et al., 2015).
this article focuses on the structural differences of AXs which influence
the health benefits. Several current articles have demonstrated that AXs
lacking of structural differences, however, resulted in different anti-
oxidant effects, the possible mechanisms are assumed in this review.
2. The molecular structure of AXs
The main structural characteristics of AXs are summarized in Fig. 1.
The linear main chain of AXs is constituted of a β-1.4-D-xylopyranosyl
backbone with L-arabinofuranosyl substituted at position 2 and/or 3 of
the furan cycle. Consequently, there are four types of substitution
pattern of xylopyranosyl: unsubstituted, monosubstituted at O-2,
monosubstituted at O-3, or disubstituted at O-2.3 (Biliaderis &
Izydorczyk, 2007; Izydorczyk & Biliaderis, 1992; Vanhamel, Cleemput,
Delcour, Nys, & Darius, 1993).
Xylopyranosyl with different substitution patterns has a diverse
ratio of arabinose to xylose, which plays an important role in depicting
the molecular structure of AXs. For example, it affects the hydrogen
bonds leading to the change of spatial arrangement of AXs (Courtin &
Delcour, 2002; Köhnke, Ostlund, & Brelid, 2011). The arabinofuranosyl
molecules of AXs presented as monosubstituted residues are mostly and
mainly monosubstituted at O-3, except isolated barley and rye fractions
with a large amount of arabinofuranosyl molecules monosubstituted at
O-2 (Cja, Delcour, Verbruggen, & Gruppen, 1995; Ebringerová,
Hromádková, Petráková, & Hricovíni, 1990; Izydorczyk & Biliaderis,
1993). As for the conformation of L-arabinofuranosyl, it has been re-
ported that the xylan backbone of new AXs is substituted by a mixture
of α- and β-anomers arabinose residues (Das, Maiti, Maiti, & Islam,
2013) although most kinds of xylan backbone were only substituted by
α-L-arabinofuranosyl. Additionally, these oligomeric side chains are
attached to each other via 1 → 2, 1 → 3, and 1 → 5 linkages, resulting in
537
Journal of Functional Foods 54 (2019) 536–551
3 2 3 2
1
1 Ara 1
5 Ara
O
Ara
1
3
2 2
1
Ara – Ara
different types of molecular structures and spatial arrangements of AXs
(Döring, Jekle, & Becker, 2016). In addition, it has been shown that
small contents of other sugar residues such as glucuronic acids, 4-O-
methyl glucuronic acid, or short oligomers consisting of L-arabinose, D-
xylose, D-galactose, D-glucose, and/or uronic acids can substitute hy-
drogen atom at O-2 position of xylose residues, while acetyl groups
substitute at O-2 and/or O-3 of xylose residues in AXs (Courtin, 2011).
Hydroxycinnamic acid derivatives, such as ferulic, coumaric, sinapic,
dehydrodiferulic acids, linked to arabinofuranosyl residues through
ester linkages with the 5-OH group (Courtin, 2011; Izydorczyk &
Dexter, 2008), can shape the dehydrodimer and dehydrotrimer isomers
to potentially crosslink polysaccharide chains and polysaccharide-pro-
tein (Dervilly-Pinel, Tran, & Saulnier, 2004; Dervillypinel, Rimsten,
Saulnier, Andersson, & Aman, 2001; Izydorczyk & Macgregor, 2000;
Mccleary & Prosky, 2008).
The molecular structure of AXs is also related to the extraction
method applied. AXs can be extracted using chemical, enzymatic, or
physical treatments. Several types of research showed that alkaline
treatment affected the functional group of AXs, lowered FA content,
and maintained the native molecule weight of AXs. On the other hand,
enzymatic treatment produced lower molecule weight AXs but with
higher FA content (Zhou et al., 2010). While physical treatments such
as extrusion cooking reduced the molecule weight of AXs because it
lowered the degree of polymerization (DP) by breaking AXs glycosidic
bonds (Nyman, 2002).
The structure of AXs depends also on the raw material that they are
originated from. AXs derived from banana peel hemicellulose and from
corn hull contained galactose or glucuronic acid (Ogawa et al., 2005;
Zhang et al., 2004). AXs derived from the green leaves of Litsea glutinosa
had a special type of branching (Das et al., 2013). Additionally, Kodo
millet contained comparatively low branched AXs with a high amount
Z. Chen et al.
of FA, p-coumaric, and caffeic acid, while glucoarabinoxylans extracted
from high tannin sorghum brans contained a high content of total
phenolic especially tannin. Altogether, it can be concluded that raw
materials and extraction method determine the molecule weight, sugar
composition, degree of substitution (DS), type of branching and total
phenolic content of AXs.
3. AXs structure related to physicochemical properties
Compared with insoluble AXs, soluble AXs have much more func-
tional properties. For instance, the existence of soluble AXs in bread
leads to improvement of dough parameters as well as bread quality
(Buksa, Nowotna, Praznik, & Gambuś, 2012). At the same time, soluble
AXs increase water content and lower the retention times of digesta in
pig thereby promoting regularity and digestive health (Zhang,
Williams, et al., 2015). It has been reported that the solubility of AXs is
determined by its structure. Arabinose: xylose ratio and the present of
FA are associated with the solubility. The unsubstituted parts of AXs
tend to aggregate through hydrogen bonds, leading to a lower solubi-
lity. An arabinose: xylose ratio lower than about 0.43 causes a drastic
drop in solubility indicating that higher arabinose: xylose ratio exerted
a positive effect on solubility (Andrewartha, Phillips, & Stone, 1979;
Courtin & Delcour, 2002; Köhnke et al., 2011; Mccleary & Prosky,
2008). The bound FA exhibits the cross-linking effect in each AX, and
consequently, decreases the solubility.
Dhital, Dolan, Stokes, and Gidley (2014) investigated that AXs in-
crease solution viscosity in vitro, thus, soluble AXs were likely thought
to form viscous digesta in the stomach as well as intestinal. The visc-
osity of AXs can change lipid and glucose metabolism. Some of the
proposed mechanisms include delaying gastric emptying, slowing the
absorption and impacting the synthesis of enzyme or hormone (Fadel
et al., 2017; Hartvigsen et al., 2014). The molecular structure of AXs
affects the viscosity properties to some extent. Comparing AXs from
wheat bran to that from two rye breads, the AXs from bran had a higher
degree of branching, which led to higher viscosity, indicating that the
degree of branching positively related to viscosity (Christensen et al.,
2013). Similarly, AXs with higher MW have higher viscosity
(Christensen et al., 2013). Likewise, the content of FA contributes to
this property as well. Bound FA demonstrates a cross-linking effect
which improves the gel-forming ability of AXs (Döring et al., 2016).
Aside from AX’s own structural features, a higher concentration of AXs
also increases the viscosity.
4. The interaction between AXs and gut microbiota
4.1. The pathway to produce short chain fatty acids (SCFAs)
Due to the nature that AXs can’t be degraded by mammalian en-
zymes, they end up in colon and are degraded by gut microbiota. Ndeh
and Gilbert (2018) showed that gut microbiota degraded AXs into
SCFAs and other products (Fig. 2). The fermentation of AXs was mainly
through the interaction with gut microbiota and catalyzed by backbone
xylan depolymerizing species, especially Bacteroidetes. It has been re-
ported that AXs were possessed by starch utilization system (Sus)-like
system encoded by polysaccharide utilization loci (PUL) from the
phylum Bacteroidetes (Koropatkin, Cameron, & Martens, 2012). The sus-
like system contained a set of polysaccharide binding-proteins (SusD
homologue; SusDH), glycolytic enzymes that hydrolyze polysaccharides
into oligosaccharides, and TonB-dependent transporters that trans-
porting these oligosaccharides into the periplasm (SusC homologue;
SusCH) (Dodd, Mackie, & Cann, 2011; Martens, Koropatkin, Smith, &
Gordon, 2011; Ndeh & Gilbert, 2018). Glycoside hydrolases on Bac-
teroidetes surface degraded AXs into arabinoxylooligosaccharides
(AXOS). AXOS then were transported into the cell periplasm by SusCH/
SusDH pairs (Glenwright et al., 2017; Ndeh & Gilbert, 2018). The de-
polymerization pathway of AXOS in cell periplasm of Bacteroidetes,
538
Journal of Functional Foods 54 (2019) 536–551
however, is still unclear. The Bacteroidetes downstream metabolism was
fermented by Firmicutes and Actinobacteria, which played important
roles in the further degradation by gram-positive PULs, analogous to
the PUL systems in Bacteroidetes (Sheridan et al., 2016). Gram-positive
PULs encoded a range of transporters, regulatory proteins, and Carbo-
hydrate-Active Enzymes to bind, degrade and transport AXs with low
DP and downstream metabolisms. The main chain of AXOS was hy-
drolyzed first, and then α-1,3- linked arabinofuranosyl residues from
AXOS were removed by glycoside hydrolases to produced xylose and
arabinose (Michlmayr et al., 2013). L. acidophilus, L. brevis, and Bifi-
dobacterium species, for instance, produced enzymes to perform these
processes (Michlmayr et al., 2013; Rivière et al., 2014). The produced
xylose then was used by some species of Bifidobacterium, such as Bi.
catenulatum and Bi longum. Arabinose was used by Bi. Dentium to gen-
erate SCFAs. Likewise, Roseburia sp. also has been shown to be able to
ferment xylose to SCFAs (Ndeh & Gilbert, 2018). AXs stimulate the
growth of gut microbiota species which affect the composition of
SCFAs. Acetate is the dominant SCFAs in AXOS treatment. After the
experiment in fish, (Geraylou et al., 2013) found that the abundant of
acetate producers, such as Clostridium spp. and lactic acid bacteria
elevated after AXOS treatment, which could be one of the reasons of the
higher amount of acetate. It has been shown that AXOS is utilized by
cross-feeding bifidobacteria and butyrate-producing colon bacteria, such
as Faecalibacterium prausnitzii (clostridialclusterIV) and Anaerostipes,
Eubacterium, and Roseburia species (clostridialclusterXIVa), to perform
the butyrogenic effects (Audrey, Marija, David, Frédéric, & Luc, 2016).
At the same time, since long-chain AXs supplementation was not ab-
sorbed in small intestinal and would progress to the caecal, it changed
the predominant habitat of the mucin-degrading Akkermansia mucini-
phila from the caecum to more distal regions, where Akkermansia mu-
ciniphila could convert mucins to propionate in humanized rats (Van
den Abbeele et al., 2011). Besides, the high amount of SCFAs inhibited
the growth of Bacteroides species (Broekaert et al., 2011).
4.2. AXs structure and microbita fermentation
Researches show that the structure of AXs is related to the gut mi-
crobiota fermentation rate and the amount of produced SCFAs
(Table 1). Vardakou et al. (2008) observed an increase in the prebiotic
index with AXs treated by xylanase compared to AXs without xylanase
treatment. Similarly, Geraylou et al. (2013) showed that a higher DP of
AXOS supplementation exerted decreased impacts on SCFA concentra-
tion compared with lower DP. More researches also showed that higher
DP reduced the fermentation rate of AXs and AXOS in human colon
(Audrey et al., 2016; Gemen et al., 2011; Pollet et al., 2012). However,
supplementation of water-extractable high MW AXs restore the number
of bacteria that are lowered upon high fat feeding (Neyrinck et al.,
2011). Van den Abbeele et al. (2011) demonstrated that long-chain AXs
with high DP significantly stimulated the production of health-pro-
moting metabolites by specific microbes in the proximal regions of the
colon in humanized rats. Damen et al. (2011) reported that feeding rat
with a higher DP water unextractable AXs diet compared with water
extractable AXs, the number of butyrate-producing bacteria like Rose-
buria and E. rectale spp. were increased, which led to increased butyrate
level in the rat’s cecum. These results suggested that AXs with high MW
or DP might have positive effects on the fermentation rate as well as
SCFA production, thus the influence of DP of AXs requires further in-
vestigation. Compared with rice AXs, maize AXs were shown to be less
branched. The bacteria were required to remove the arabinose before
being able to utilize xylose of rice AXs, but the maize AXs with com-
paratively less branched resulted in easy access for bacteria to reach
xylose and generate higher SCFAs production (Rose, Patterson, &
Hamaker, 2010). Therefore, highly branched oligosaccharides are
poorly fermented (Rose et al., 2010). Meanwhile, fermentation patterns
of maize, rice and wheat AXs were different. Maize and rice AXs were
degraded by a debranching mechanism while wheat AXs were firstly
Z. Chen et al.
diet colon
Bacteroidetes
AX AX AX
AX
AXOS AXOS
AXOS AXOS
starch utilization system (Sus)-like system
ATP-binding cassettes transporters
Cation symporter family transporters
Major facilitator superfamily transporters
PEP-phosphotransferase system transporters
endoxylanase
arabinofuranosidase
xylosidase
degraded by bacteria in its unsubstituted region followed by their
arabinose side chains being metabolized, indicating a two-phase me-
tabolism (Banuls et al., 2016). Thus, DS is an important structural factor
associated with the fermentation, which influences not only SCFA
production, but also fermentation mechanisms. Chen et al. (2017) in-
vestigated that sorghum bran AXs were fermented more rapidly com-
pared to corn AXs due to the different branched structure. Both of
sorghum bran AXs and corn AXs had similar molecular size but corn
AXs had a more complex composition of sugars and linkage patterns
compared to sorghum bran AXs in which the xylan backbone was
Table 1
Effects on interaction with gut microbiota.
Molecular structure
AXs (avDP = 60, avDS = 0.70)
AXs (avDP = 284, avDS = 0.59)
AXs from wheat bran (Ara/Xyl ratio, 1.14; contained a complex
trisaccharide side chain; high amounts of branches with single
xylose units); sorghum AXs (Ara/Xyl ratio, 1.08; contained the
highest degree single arabinosebranches)
AXs from maize bran (Ara/Xyl ratio, 0.52) AXs from rice bran (Ara/
Xyl ratio, 1.12)
Sorghum bran AXs (contained uniform arabinose substitution); corn
AXs (complex array of sugars and linkage patterns)
AXOS1 (avDP = 3); AXOS2 (avDP = 12)
AXOS1 (high bound FA content); AXOS2 (high free FA content);
AXOS3 (low FA content)
AXOS1 (avDP = 32, avDS = 0.30); AXOS2 (avDP = 3, avDS = 0.25)
avDP, average degree of polymerization; avDS, average degree of substitution; Ara/Xyl Ratio, arabinose/xylose ratio; AXs, arabinoxylans; AXOS, arabinox-
ylooligosaccharides; FA, ferulic acid; SCFAs, short chain fatty acids.
Journal of Functional Foods 54 (2019) 536–551
Fig. 2. Depiction of the possibly process of
the interaction between gut microbiota and
arabinoxylans (AXs) and its hydrolysis pro-
Firmicutes and Actinobacteria ducts arabinoxylooligosaccharides (AXOS),
to produce short chain fatty acids (SCFAs).
AX XOS The AXs fermentation pattern of
Bacteroidetes is through starch utilization
system (Sus)-like system encoded by poly-
saccharide utilization loci (PUL). AXs may
X degrade by glycoside hydrolases (possibly
AXOS endoxylanase) on the surface into AXOS.
A SCFA AXOS may be transported into the cell
periplasm by SusCH/SusDH pairs. The de-
polymerization pathway of AXOs in cell
periplasm of Bacteroidetes is unclear. Beside
SCFA
Bacteroidetes, Roseburia from Actinobacteria
has the ability to degrade AX as well. The
AXs and Bacteroidetes downstream metabo-
lism can be transported into Firmicutes or
Actinobacteria through four kinds of prob-
able transporters and depolymerized by
carbohydrate-Active Enzymes which en-
coded by gram positive PULs. AXs are in-
itially degrade by endoxylanase into AXOS
followed by AXOS linkage breakdown by
arabinofuranosidase and xylosidase into
arabinose (A) and xylose (X). Secondly, the
produced xylose (X) and arabinose (A) can
be used by some species of Bifidobacterium
and Roseburia to acquire SCFAs.
substituted by the relatively uniform arabinose. The complexity of the
AXs molecules was shown to strongly influence the fermentation rate
(Chen et al., 2017). This opinion was also confirmed by Rumpagaporn’s
observation that a slow fermentation rate of AXs was associated with
more branches, single xylose units, or the unusual trisaccharide branch
chains in AXs (Rumpagaporn et al., 2015). Mendis, Martens, and
Simsek (2018) investigated the fine structure of AXOS and XOS influ-
ence the growth of Bacteroides species in the intestine, which suggested
that 23– α-L-arabinofuranosyl-xylotriose could elevate the expression of
small xylan PUL gene while 23, 33 -di- α-L-arabinofuranosyl-xylotriose
Effect on interaction with gut microbiota In vivo/in vitro Reference
Stimulate bacterial species with butyrate In vivo, rats (Van den Abbeele et al.,
producing ability and bifidobacteria. Reduced 2011)
caecal abundances of Akkermansia muciniphila
Increased the number of butyrate producing In vivo, rats (Damen et al., 2011)
bacteria like Roseburia and E. rectale spp.
AXs from wheat bran fermented slowly compared In vitro, human fecal (Rumpagaporn et al.,
to sorghum AXs due to the branched structure fermentation analyse 2015)
differences.
Less branched maize AXs resulted in the highest In vitro, digestion and (Rose et al., 2010)
SCFA production. fermentation analyse
Sorghum bran fermented rapidly compared to corn In vitro, human fecal (Chen et al., 2017)
AXs due to the branched structure differences fermentation analyse
High avDP AXOS has slower fermentation rate In vitro, human fecal (Snelders et al., 2014)
compared with AXOS with low avDP fermentation analyse
Both bound and free FA inhibited AXOS In vitro, human fecal (Snelders et al., 2014)
fermentation fermentation analyse
AXOS (avDP = 32, avDS = 0.30) has higher In vivo, fish (Geraylou et al., 2013)
impact on SCFAs production and more pronounced
effects on stimulation of Lactobacillaceae
539
 Z. Chen et al.

Table 2
Effect on metabolism of AXs with different structural features.
Sources Molecular structure Effect on metabolism In vivo/in vitro Reference

Effect on lipid metabolism

Wheat bran Ara/Xyl ratio, 0.58 Increase postprandial fat utilization In vivo, mice (Hosoda et al., 2017)
Wheat bran MW, 602 kDa; Ara/Xyl ratio, 0.9 Increase fatty acid oxidation; reduce plasma cholesterol; increase ileal viscosity In vivo, diabetic fatty rats (Hartvigsen et al., 2013)
Wheat bran Ara/Xyl ratio, 0.47 Decrease circulating bile acids In vitro, 13C NMR and SAXS experiments (Gunness, Flanagan, et al., 2016; Gunness,
Williams et al., 2016)
Wheat bran MW, 63.2–3470 kDa Reduce plasma cholesterol In vivo, hypercholesterolemic hamsters (Tong et al., 2014)
Wheat bran Ara/Xyl ratio, 0.7 Decrease lipid synthesis in adipose tissue In vivo, obese mice (Neyrinck et al., 2011)
Finger millet Ara/Xyl ratio, 0.78 Decrease lipid synthesis in liver In vivo, mice (Sarma et al., 2018)
Rye Ara/Xyl ratio 0.45 Decrease circulating bile acids In vitro (Gunness, Flanagan, et al., 2016; Gunness,
Williams et al., 2016)
Corn bran avDS = 0.64 Reduced cholesterol uptake. Decreased serum cholesterol levels. Inhibited In vivo, rats (Lopez et al., 1999)
cholesterol accumulation in liver.
Wheat bran AXOS (contained FA) Inhibited lipid peroxidation in serum, liver and testes. In vivo, diabetic rats (Shiyi Ou et al., 2007)

540
Wheat bran AXOS Reduced body weight, fat mass and plasma leptin levels. In vivo, mice (Suriano et al., 2017)

Effect on glucose metabolism

Wheat bran MW, 602 kDa; Ara/Xyl ratio, 0.9 Increase glycolysis; increase ileal viscosity; attenuate plasma glucose In vivo, diabetic fatty rats (Christensen et al., 2013)
Wheat bran Ara/Xyl ratio, 1.23; contained FA Inhibit glucose transporter 2 and α-glucosidase In vitro (Malunga et al., 2016)
Destarched bran Cross-linked AXs Remained viscous in theintestinal and lowered the postprandial blood glucose In vivo, rats (Vogel, Gallaher, & Bunzel, 2012)
level.
Wheat flour avDS = 0.8 Reduced postprandial serum glucose, insulin and blood plasma ghrelin. In vivo, human (Garcia et al., 2007; Garcia et al., 2006)
Decreased fasting serum glucose
Wheat flour avDS = 0.8 Lowered postprandial serum insulin; elevated postprandial blood plasma ghrelin. In vivo, human (Möhlig et al., 2005)
Wheat flour avDS = 0.66 Decreased fasting serum glucose levels. Reduced serum glucose levels and insulin In vivo, human (Lu, Walker, Muir, & O'Dea, 2004)
concentration 2 h after oral glucose intake.
Wheat bran AXOS (Ara/Xyl ratio, 0.2–0.3; MW, Reduced metabolic endotoxemia thereby inhibiting insulin resistance In vivo, diabetic rats (Neyrinck et al., 2012)
below 0.59 Da)
Wheat bran AXOS (contained FA) Inhibited weight loss of diabetic; down regulated serum glucose level. In vivo, diabetic rats (Shiyi Ou et al., 2007)

avDS, average degree of substitution; Ara/Xyl Ratio, arabinose/xylose ratio; MW, molecular weight; AXs, arabinoxylans; AXOS, arabinoxylooligosaccharides; FA, ferulic acid.
Journal of Functional Foods 54 (2019) 536–551
Z. Chen et al.
lowered the expression. Furthermore, the presence of feruloylated and
diferuloylated arabinose substituents reduced the fermentability of AXs
and AXOS, because bound FA probably hindered enzyme activity
sterically, but bound FA did not impact the SCFA ratio (Hopkins et al.,
2003; Snelders, Dornez, Delcour, & Courtin, 2013; Snelders et al.,
2014).
Above all, it can be concluded that the DP, DS, chemical composi-
tion and linkage-type of the branches, all together, affect the rate of
fermentation of gut microbiota. AXs with lower molecule weight, lower
DS, less FA content and simple linkage and sugar pattern will lead to a
higher fermentation rate and generate more SCFAs. It is widely known
that the fermentation product SCFAs exert beneficial physiological
functions in human. Therefore, it is possible that the structural of AXs
influenced AXs’ health effects through changing the fermentation rate
and SCFAs production.
4.3. The change of gut microbiota
The interaction between AXs and gut microbiota takes place in the
intestine, the abundance and the composition of intestinal flora are
likely to be changed after AXs supplementation. Several research
groups observed that the numbers of Roseburia intestinalis, Eubacterium
rectale, Anaerostipes caccae, Clostridium clusters XIVa, and some other
saccharolytic colon bacteria, such as Bacteroides spp. as well as
Lactobacillus spp. increased in rats upon AXs supplementation (Damen
et al., 2011; Van den Abbeele et al., 2011). However, AXs have been
shown to be rarely bifidogenic (Broekaert et al., 2011). At the same
time, the studies on AXOS (the hydrolytic degradation products of AXs)
showed that after feeding fish (juvenile Siberian sturgeon) with a diet
containing 2% AXOS, the amount of Eubacteriaceae, Streptococcaceae,
Lactobacillaceae, Lactococcus lactis, and Bacillaceae increased (Geraylou
et al., 2013). Likewise, it has been demonstrated that the levels of bi-
fidobacteria, lactobacilli, and Eubacterium rectale were increased, while
that of Bacteroides was reduced upon AXOS supplementation in vitro
during fermentation by human gut derived microbiota (Audrey et al.,
2016; Sanchez et al., 2009; Snelders et al., 2014). Using the experi-
mental setup constituted two identical units of the SHIME, Grootaert
et al. (2009) investigated that AXOS degradation in the colon was in-
dicated to be compartment-specific depending on their average DP.
Those with an average DP lower than 15 were almost completely uti-
lized in the ascending and transverse colon compartments in the si-
mulator of human intestinal (Sanchez et al., 2009). As for the AXOS
with an average DP of 29, the abundance of bifidobacteria in the as-
cending colon, lactobacilli in both ascending and transverse colons was
augmented (Sanchez et al., 2009). It seems that AXs and AXOS exert an
inconsistent impact on the abundance and the composition of gut mi-
crobiota, especially in Bifidobacterium and Bacteroides. This inconsistent
impact is likely attributed to the different structure of AXs and AXOS.
Bifidobacterium species mainly produce xylosidases and arabinofur-
anosidases while Bacteroides mainly produce endoxylanase (Broekaert
et al., 2011; Chassard, Goumy, Leclerc, Del'Homme, & Bernalier-
Donadille, 2010; Lambertusam & Alphonsgj, 2008; Zeng, Xue, Peng, &
Shao, 2007). For the AXs with high DP, they tend to be degraded by
endoxylanase which stimulated the growth of Bacteroides. While for the
AXOS with the low DP, it is easier to be accessed by xylosidases and
arabinofuranosidases to produce xylose and arabinose, and conse-
quently the abundance of Bifidobacterium. increases. Furthermore, long-
chain AXs supplementation has been shown to increase caecal mucin
level by lowering caecal abundances of the mucin-degrading Akker-
mansia muciniphila (Van den Abbeele et al., 2011).
AXOS supplementation inhibited Salmonella colonization in broiler
chickens (Eeckhaut et al., 2008). Salmonella is a pathogenic bacteria
and is harmful to human health. Likewise, since AXOS can stimulate
acetate and propionate production thereby lower the pH in intestinal, it
also inhibits the growth of E. coli in vitro (Cherrington, Hinton, Pearson,
& Chopra, 2010).
541
Journal of Functional Foods 54 (2019) 536–551
The physicochemical properties and the interaction with gut mi-
crobiota can be influenced by AXs’ structural features. Further more,
the physicochemical properties of AXs performed in vivo and the
change in the composition of gut microbiota may be the mechanisms to
explain the physiological functions of AXs. Nowaday, the physiological
functions of AXs are receiving growing attention. We analyzed the
mechanisms of AXs to perform health benefits and discussion the re-
lationship between AXs structure and physiological functions.
5. Physiological functions of AXs
5.1. The effect of AXs on lipid metabolism
Several studies investigate the physiological function in lipid me-
tabolism of AXs with different structures (Table 2). AXs are able to
increase lipid excretion in feces of mice due to its fat binding capability
(Neyrinck et al., 2011; Suriano et al., 2017). The fat binding capability
can be one of the mechanisms explaining the decline in ectopic lipid
accumulation in the liver tissue, which can attribute to the decrease in
dietary nonesterified fatty acids that redistributed from the adipose
tissue to the liver (Suriano et al., 2017). After the experiment in rats,
Lopez et al. (1999) investigated that soluble corn bran AXs declined the
uptake of cholesterol from a cholesterol-rich diet, leading to the de-
creased in total cholesterol as well as low-density lipoprotein (LDL)-
cholesterol in the plasma. Additionally, the absorption of lipids in-
cluding long chain fatty acid-like linoleic acid and cholesterol was
slowed down by AXs in diabetic fatty rats, possibly through increasing
the viscosity of the surrounding intestinal digesta (Gunness, Flanagan,
Shelat, Gilbert, & Gidley, 2012; Hartvigsen et al., 2013). After the ki-
netic analysis in vitro, it has been observed that increased viscosity of
the surrounding intestinal bolus led to the inhibition of the contents
mixing with the unstirred water layer thereby elevated the effective
thickness of the unstirred water layer (Gunness et al., 2012). This thick
viscous unstirred water layer was composed of a diffusion barrier for
the absorption and the augment in its thickness led to lower lipid ab-
sorption (Gunness et al., 2012). It was also believed that AXs lowered
the speed of triglycerides digestion as well as free fatty acids assim-
ilation through decreasing circulating bile acids (BA), leading to re-
duced blood triglycerides level in pigs (Gunness, Williams et al., 2016).
AXs interacted with BA through dynamic molecular interaction or
polysaccharide aggregates entrapment in vitro (Gunness, Flanagan,
Mata, Gilbert, & Gidley, 2016). BA is an important substance con-
tributing to dissolve and transit hydrophobic entities (Shelat et al.,
2010). Besides, the arabinose residues of AX’s side chain contribute to
reducing BA absorption, due to its ability to infiltrate into hydrophilic
head of BA micelles (Gunness, Flanagan, et al., 2016). Nie et al. (2018)
showed that AXs treatment reduced the amount of acetoacetate,
acetone, and choline in type 2 diabetic rats thereby played a role in
lipid metabolism. The fatty acid metabolism in the liver mitochondria
produces acetoacetate and acetone, two main products in ketone body’s
metabolism.
Besides the impact on digestion of lipid, the gene expression of lipid
is beneficially regulated by AXs supplementation in the liver. The ex-
periments in mice was observed that AXs have been shown to decrease
lipogenic gene expression such as fatty acid synthase, acetyl-CoA car-
boxylase, sterol regulatory element-binding protein-1, and upregulate
fatty acid oxidation gene expression, for instance, acyl-CoA oxidase-1,
Cyp4a10, Cyp4a14 and cytochrome p450, suggesting AXs reduced li-
pogenesis and increased β-oxidation thereby decreased lipid accumu-
lation in the liver and decreased triglycerides in the serum and in the
liver (Kieffer et al., 2016; Sarma et al., 2018). AXs also have been
shown to increase expression of cholesterol 7- alpha-hydroxylase to
accelerate cholesterol catabolism and BA synthesis in hamsters (Tong
et al., 2014). Likewise, AXs decrease cholesterol synthetic gene ex-
pression such as 5-hydroxy-3-methlgutaryl-coenzyme A reductase and
3-hydroxy-3-methylgulutaryl-CoA synthase due to elevated propionate,
Z. Chen et al.
to exert hypocholesterolemic effect in vivo (Chen et al., 2018; Tong
et al., 2014). Furthermore, in high-fat diet induced rats, liver damage in
rats can be relieved by AXs supplementation due to the regulation of
liver cell apoptosis and a decrease of the lipid hydroperoxides (Chen
et al., 2018).
The gene expression in adipose tissue is modulated by AXs supple-
mentation as well. Sarma et al. (2018) showed that AXs supplementa-
tion regulated peroxisomeproliferator-activated receptor gamma,
CCAAT/enhancer-binding protein alpha and delta-like-1 of mice, to
modulate transformation rate of preadipocytes into mature adipocytes.
The transformation rate was correlated with adipocyte hyperplasia. At
the meantime, AXs supplementation may also decrease fatty acid syn-
thase and downregulates peroxisome proliferator-activated receptor
alpha, elevates acyl-CoA oxidase-1 expression through stimulating
propionate production in vivo, suggesting that it decreases lipid
synthesis and increases lipid breakdown (Heimann, Nyman, &
Degerman, 2015; Hosseini, Grootaert, Verstraete, & Van de Wiele,
2011; Neyrinck et al., 2011). Consequently, adipocyte hypertrophy is
decreased in visceral white adipose tissue. AXs can modulate adipocyte
hypertrophy and adipocyte hyperplasia which are the two factors
contributed to adipose tissue mass augment (Jiang, Jo, & Graff, 2012).
In white adipose tissue, fasting-induced adipose factor expression is
downregulated after AXs supplementation in the high fat diet. Using
transgenic mice with over-expressed fasting-induced adipose factor,
Neyrinck et al. (2011) observed that fasting-induced adipose factor
could elevate total cholesterol as well as high-density lipoprotein cho-
lesterol levels. Moreover, AXs can inhibit lipolysis and de novo lipo-
genesis in adipose tissue through stimulating propionate production in
vivo, which plays an important role in preventing ectopic fat deposition
and lipotoxicity (Heimann et al., 2015).
The interaction of AXs with gut microbiota influences lipid meta-
bolism. It has been reported that in rats which were supplied with a
high-fat diet and the obese adults had a high endogenous acetate pro-
duction, a probable biomarker leading to metabolic syndrome (Chen
et al., 2018). Long-chain AXs were able to decrease acetate production
through transforming acetate into health-promoting propionate and
butyrate in rats or mice (Berger et al., 2014; Fadel et al., 2017; Van den
Abbeele et al., 2011). Heimann et al. (2015) showed that propionate
and butyrate changed the gene expression in the adipose tissue of rats
to decrease lipid synthesis and increase lipid breakdown. Likewise, they
prevented ectopic fat deposition and lipotoxicity through inhibition of
lipolysis and de novo lipogenesis. AXs supplementation increases Ro-
seburia spp while AXOS supplementation elevates both Bifidobacteria
and Roseburia spp. in mice (Druart et al., 2013; Neyrinck et al., 2011).
Bifidobacteria and Roseburia spp are able to metabolize linoleic acid into
conjugated linoleic acid isomers (Druart et al., 2013; Neyrinck et al.,
2011). At the same time, AXs supplementation elevated linoleic acid’s
availability for the gut microbiota in the lower part of the gut, due to its
fat binding capacity (Druart et al., 2013). Both properties contribute to
a higher production of conjugated linoleic acid (Druart et al., 2013;
Neyrinck et al., 2011). It has been reported that conjugated linoleic acid
can inhibit the enzymes related to mammary lipid synthesis (Bauman,
Harvatine, & Lock, 2011). Neyrinck et al. (2018) believed that AXOS
supplementation exerted bifidogenic effect associated with a decrease
in body weight, reduced fat mass, and attenuated plasma leptin levels in
mice. Interestingly, such effects did not depend on caloric intake or the
regulation of peptides affecting appetite such as ghrelin or glucagon-
like peptide 1 (GLP-1) (Neyrinck et al., 2018).
The ability of AXs to modulate lipid metabolism is related to glucose
metabolism. A diet containing AXs causes a reduction of the post-
prandial blood glucose-dependent insulinotropic polypeptide response
in mice, leading to an increase in postprandial energy catabolism and
prevention of obesity (Hosoda et al., 2017; Neyrinck et al., 2018).
Glucose-dependent insulinotropic polypeptide is a gastrointestinal in-
cretin hormone, which promotes pancreatic β cells to secrete insulin.
Likewise, the liquid chromatography–MS metabolomics analysis of
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Journal of Functional Foods 54 (2019) 536–551
plasma from portal–arterial catheterised pigs was conducted, the results
shown that AXs supplementation caused a reduction of glucose uptake,
leading to a lower concentration of lysophosphatidylcholine (Nielsen,
Hedemann, Laerke, Jorgensen, & Bach Knudsen, 2014). Lysopho-
sphatidylcholine is elevated in the acquired obesity and is the main
plasma lipid component of oxidized LDL, suggesting that high lyso-
phosphatidylcholine concentration likely result in chronic inflamma-
tion as well as atherosclerosis (Nielsen et al., 2014).
The structure of AXs influences AXs’ ability of lipid metabolism
modulation. Viscosity of AXs plays an important role in fat binding
capacity, lipid and BA absorption. Thus, the structural features of AXs
may change the viscosity to exerts effect on AXs’ ability of lipid meta-
bolism modulation. Moreover, at the same time, SCFAs are of great
significance in modulating lipid metabolism. The structural features of
AXs can change the interaction with gut micromiota of AXs thereby
influence the production of SCFAs. However, although several animals
experiments demonstrated that AXs supplementation change the gene
expression in liver or adipose tissue, the mechanism of them are still
unclear. Further researches may need to focus on the bioactive fraction
of AXs leading to the change in gene expression, and figure out whether
gut microbiota are involve in the mechanism.
5.2. The effect of AXs on glucose metabolism
The effects of various soluble AXs on glucose metabolism have been
documented (Table 2). The soluble AXs likely delay gastric emptying,
slow small intestinal transit, reduce the rate of glucose diffusion, de-
crease the availability of digestive enzymes, and mediate intestinal
mobility, all contribute to lower the absorption of glucose and an at-
tenuated postprandial glycemic response (Dhital et al., 2014; Giulia
Falchi, Grecchi, Muggia, Palladini, & Perlini, 2016; Juvonen et al.,
2009; Vangsøe et al., 2016). Additionally, the gel-forming property of
soluble AXs is able to slow down the protein degradation and absorp-
tion. Thus, the level of amino acid is decreased and lead to an atte-
nuated insulin response (Christensen et al., 2013). Viscosity, or gel-
forming capacity, is a physicochemical property associated with AXs,
which is one of the mechanisms of AXs’ ability of affecting short-term
postprandial glucose level2. The effect, however, may be offset by
strong intestinal peristalsis, indicating that it would not be the principal
factor of reducing the digestion rate in the intestine (Dhital et al., 2014;
Gemen et al., 2011). The high or low viscosity of AXs relates to different
physiological functions. It has been reported that high viscosity exerted
beneficial effects on glycemia and insulinemia due to slower gastric
emptying rate (Juvonen et al., 2009). A higher nutrient-mediated GLP-
1, however, was triggered by a reduction of viscosity, which facilitated
insulin synthesis as well as evoked cholecystokinin and peptide YY re-
sponse (Hartvigsen et al., 2014; Juvonen et al., 2009). Therefore, the
ghrelin release was inhibited with the improvement in a sense of satiety
(Hartvigsen et al., 2014; Juvonen et al., 2009). It can be concluded that
high viscous AXs are apt to reduce postprandial glucose level than low
viscous AXs, but are more difficult to improve a sense of satiety and
may lead to higher energy intake for a healthy subject. The molecular
structures of AXs that affect the viscosity properties including MW,
arabinose: xylose ratio and the degree of branching (Christensen et al.,
2013; Gemen et al., 2011). Furthermore, the food processing method(s),
as well as the combination of foods and drinks during a meal will also
result in different AXs viscosity (Gemen et al., 2011; Pantophlet et al.,
2
In rats, a diet with low viscosity AXs did not have ability to decrease
postprandial glucose, however, cross-linking of the AXs remarkably elevated
viscosity and attenuated the glucose response (Vogel et al., 2012).In a research
conducted by Wood et al. (1994), nine human subjects consumed liquid meals
contained glucose and different concentration of oat gum. It was observed that
the plasma glucose concentration reduced when the subjects consumed high
viscosity of oat gum.
Z. Chen et al. Journal of Functional Foods 54 (2019) 536–551

avDP, average degree of polymerization; avDS, average degree of substitution; Ara/Xyl Ratio, arabinose/xylose ratio; MW, molecular weight; AX, arabinoxylan; AXOS, arabinoxylooligosaccharides; FA, ferulic acid; PAP,
2017).

(Samuelsen et al., 2011)

(Cholujova et al., 2013)

(Neyrinck et al., 2012)

(Niewold et al., 2012)
By inhibiting mammalian intestinal α-glucosidase (sucrase and

(Kamiya et al., 2014)

(Zhang et al., 2004)

(Zheng et al., 2012)
(Zhou et al., 2010)
(Zhou et al., 2010)
(Cao et al., 2011) maltase) and reducing glucose transporter 2 activities, feruloylated

(Das et al., 2013)

arabinoxylan mono/oligosaccharide shows an antihyperglycemic ef-
fect. The inhibitory activity is attributed to FA moiety, an effective part
Reference

of feruloyl arabinoxylanmono/oligosaccharide (Malunga, Eck, & Beta,

2016). In the diabetic fatty rats fed with AXs contained diet, the ex-
pression of fat-binding protein 2 was upregulated, consistent with the
In vivo, S180tumor-bearing mice

higher insulin level. Fat-binding protein 2 was thought to be related to

improvement of insulin sensitivity (Hartvigsen et al., 2013). Using type
2 diabetic rats, Nie et al. (2018) observed reduction in pyruvate
vivo, broiler chicks

vivo, diabetic rats

through high-dose Plantago asiatica L. AXs supplementation. Pyruvate is
an important product in glycolysis, suggesting that AXs supplementa-
In vivo/in vitro

In vivo, human

In vivo, human

vivo, piglet

tion is able to attenuate glycolysis in type 2 diabetic rats from the

In vivo, rats
In vivo, rats

In vivo, rats

general view (Nie et al., 2018). However, in adipose tissue, an aug-

vitro
vitro

mented level of insulin followed by up-regulated adipose glycer-

aldehyde-3-phosphate dehydrogenase expression was observed in the
In
In
In
In
In

diabetic fatty rats fed with AXs contained diet. Glyceraldehyde-3-

Stimulated immature dendritic cell maturation. Augmented NK cytolytic activity
had the ability to reduce the IL-8 concentration, exerted a protective effect on

phosphate dehydrogenase participates in glycolysis, indicating that AXs

Strengthens T and B cell functions, elevates lymphocyte ratio, decreases the
Stimulated macrophage phagocytosis and delayed hypersensitivity reaction

promoted glycolysis in the adipose tissue (Hartvigsen et al., 2013),

specific mechanism need further exploring. In addition, AXs supple-
increase in antibacterial protein PAP to against acute ETEC challenge
Improve NK cells cytotoxic activity and activation of T and B cells

mentation restores tricarboxylic acid cycle intermediates in urine (2-

Induced expression of IL-10 to perform anti-inflammatory effect.

oxoglutarate, succinate, and malate), which normally is elevated in

type 2 diabetic rats, indicating that AXs have the ability to inhibit
Strong splenocyte, thymocyte, and macrophage activations
exerted effects on innate and acquired immune responses

diabetes triggered augment of tricarboxylic acid cycle (Nie et al., 2018).

Kieffer et al. (2016) reported that enzyme-treated wheat bran-fed mice
(AXs and AXOS were the main components of diet) showed an upre-
gulated expression of phosphoenolpyruvate carboxykinase 1 and glu-
Elevated macrophages activation in vitro

cose-6-phosphatase. Phosphoenolpyruvate carboxykinase 1 is a speed-

limiting enzyme for gluconeogenesis while glucose-6-phosphatase is
related to gluconeogenesis and glycogenolysis through gut-derived
Low immunological responses

signals. Thus, enzyme-treated wheat bran supplementation modulated

Effect on the immune system

both gluconeogenesis and glycogenolysis which might play important

roles in glucose homeostasis in the liver (Kieffer et al., 2016).
AXs and AXO supplementation cause an important bifidogenic effect
neutrophil ratio

by promoting L cells’ GLP-1 and glucagon-like peptide 2 (GLP-2) pro-

duction (Neyrinck et al., 2012). GLP-1 is an intestinal peptide capable
hepatitis

of regulating food intake and glucose homeostasis. The augment of

GLP-2 promotes the improvement of intestinal barrier function to pre-
vent metabolism endotoxemia through increasing the expression of
Low molecular weight fraction of MGN-3 (MW lower than

tightly bound proteins (Broekaert et al., 2011; Neyrinck et al., 2012).

Metabolism endotoxemia is one of the triggering factors leading to the
AXOS (Ara/Xyl ratio, 0.2–0.3; MW, below 0.59 Da)

development of insulin resistance (Geurts, Neyrinck, Delzenne, Knauf,

Ara/Xyl ratio, 0.56; MW, 32.5 kDa; contained FA

& Cani, 2014; Neyrinck et al., 2012). In addition, consumption of the

MGN-3 (Ara/Xyl ratio, 0.5; MW, 30–50 kDa)

MGN-3 (Ara/Xyl ratio, 0.5; MW, 30–50 kDa)

AXs-rich diet increased SCFAs absorption and, in particular, butyrate

Effect on the immune system of AXs with different structural features.

absorption (Ingerslev, Theil, Hedemann, Lærke, & Bach Knudsen,

AXOS (avDP = 5, Ara/Xyl ratio, 0.21)

2014). Higher butyric acid uptake elevates glucose intake in adipocytes

Ara/Xyl ratio, 0.83; MW, 351 kDa

stimulated by insulin and particularly improves peripheral insulin

sensitivity by affecting adipose tissue as well as circulating non-
pancreatitis associated protein; ETEC, Escherichia coli.

esterified fatty acids. Insulin sensitivity may increase glucose tolerance

in an overnight perspective (Boll et al., 2016; Heimann et al., 2015;
Molecular structure

Ingerslev et al., 2014). Propionate stimulates the production of GLP-1 in

MW, 351 kDa

MW, 175 kDa

MW, 156 kDa
MW, 288 kDa

the gut and improves satiety by promoting insulin synthesis which re-
sults in inhibition of ghrelin release (Broekaert et al., 2011). Likewise,
400 Da)

propionic acid or, to some extent, butyric acid, can affect basal lipolysis,
which may exert some positive effects on glucose homeostasis in me-
tabolic disorders (Heimann et al., 2015). AXs also increase absolute
Green leaves of Litsea glutinosa

concentration of acetic acid, inhibit insulin-stimulated glucose uptake,

and suppress insulin signaling by inhibiting the protein kinase B in 3T3-
L1 adipocytes and primary adipocytes cells of mice (Heimann et al.,
2015; Kimura et al., 2013; Van den Abbeele et al., 2011). It seems that
small intestinal microbiome is able to break down AXs into arabinose
banana peel
Wheat bran
Wheat bran
Wheat bran

Wheat bran
Wheat bran

and xylose (Pantophlet et al., 2017). Arabinose itself reduces the starch-
Rice bran

Rice bran
Rice bran
Sources

derived glucose production via suppressing maltase activity in the small

Table 3

Barley

intestine (Jurgoński, Krotkiewski, Juśkiewicz, & Billing-Marczak,

2015).

543
Z. Chen et al.
Same as the effect of AXs on lipid metabolism, it has been observed
that AXs change gene expression related to glucose metabolism, how-
ever, the mechanisms are still unclear. It is possible that the bioactivate
fractions of AXs change the gene expression or AXs change the com-
position of gut microbiota thereby modulating the gene expression.
Likewise, the ability of AXs to decrease glucose level in plasma may
lead to body adjusted function. This may also be one of the mechanisms
to explain the change in gene expression.
5.3. The effect of AXs on the immune system
The immune-enhancing function of AXs have been studied
(Table 3). AXs from wheat bran, 3.517 × 105 Da MW, enhance the
macrophage phagocytosis of chicken red blood cells and improve the
cytotoxic activity of NK cells against derived tumor cells. Meanwhile,
AXs remarkably elevate concanavalin A level and promote lipopoly-
saccharide-stimulated splenocyte proliferation in S180 tumor-bearing
mice. They also dose-dependently increase IL-2 secretion in the blood
serum. All these effects contributed to the activation of T and B cells
(Cao et al., 2011). It has been reported that AXs increased total im-
munoglobulins (Igs), immunoglobulin (Ig)G and IgM anti-sheep red
blood cells antibody titers in chickens (Akhtar et al., 2012). A higher
level of anti- sheep red blood cells IgM antibody titers has been asso-
ciated with attenuated humoral immunity, possibly due to that AXs
were able to strength physiological and infectious insults resistance
(Akhtar et al., 2012). Likewise, AXs from corn hull, 5.06 × 105 Da MW
and contained D-galactose and α-D-glucuronic acid, elevate NK cell
activity and spleen cells’ TNF-α secretion in the presence of con-
canavalin A and lipopolysaccharide leading to a lower tumor growth
rate during the early stages after tumor transplantation (Ogawa et al.,
2005). Similarly, AXs from banana peel hemicellulose, 2.88 × 105 Da
MW and contained galactose, elevate macrophages activation in vitro
(Zhang et al., 2004). Zhou et al. (2010) investigated the immune-en-
hancing function of alkaline extracted AXs (AXA) (MW = 3.517 × 105
Da) and enzyme-extracted AXs (AXE) (MW = 3.252 × 104 Da). Com-
paring with AXA, AXE stimulated higher macrophage phagocytosis and
showed a more delayed hypersensitivity reaction (Zhou et al., 2010).
Meanwhile, medium MW (1.56 × 105 Da) AXs isolated from barley
showed lower immunological responses (Samuelsen et al., 2011) while
arabinoxylan from the green leaves of Litsea glutinosa with a similar
level of MW (1.75 × 105 Da) showed stronger splenocyte, thymocyte,
and macrophage activation (Das et al., 2013).
MGN-3, a kind of AXs produced by enzymatic modification from
rice bran, promotes the differentiation of human blood monocytes into
immature dendritic cells through a reduction of CD14 monocyte ex-
pression marker. Likewise, it triggers a significant increase in CD83,
CD80, and the CD86 expression on immature dendritic cells and sti-
mulated immature dendritic cell maturation, which in turn delivers co-
stimulatory signals for effector T cells (Cholujova et al., 2013; Zhang,
Li, et al., 2015). MGN-3 significantly promotes NK cell cytotoxicity,
activation, and expansion by inducing IFNγ, TNF-α, and CD54, CD69,
CD25 receptors (Cholujova et al., 2013; Perez-Martinez et al., 2015).
Furthermore, in the presence of IL-2, NK cytotoxicity can be increased
(Cao et al., 2011; Perez-Martinez et al., 2015). Moreover, MGN-3
strengthens T and B cell functions, elevates lymphocyte ratio as well as
decreases the neutrophil ratio prominently (Kamiya et al., 2014; Zhang,
Li, et al., 2015). Several studies investigated the anti-tumor property of
MGN-3. It increases the apoptosis of cancer cell lines by activating
caspase 8, caspase 9, and caspase 3, depolarising mitochondrial mem-
brane potential, and inhibiting Bcl-2 (anti-apoptotic protein) expression
(Ghoneum & Gollapudi, 2003). Another alternative mechanism for
MGN-3′s anti-tumor effects may be involving the activation of various
endogenous antioxidant enzymes, for instance, GPx, SOD1, CAT, GST,
and reduction of lipid peroxidation (Zhang, Li, et al., 2015). Zheng,
Sanada, Dohi, Hirai, and Egashira (2012) used 1N HCl to hydrolyzed
MGN-3 at 100 °C for 1 h. The MGN-3 hydrolysate had the ability to
544
Journal of Functional Foods 54 (2019) 536–551
reduce the IL-8 concentration and its mRNA expression level, which
exerted a protective effect on D-GalN-induced hepatitis, indicating that
low MW compounds in MGN-3 seemed to be effective (Zheng et al.,
2012).
AXs supplementation can lower pH of the cecal (Chen et al., 2015).
Low pH level has been shown to inhibit the number of pathogenic
bacteria, thus, is considered to be beneficial (Chen et al., 2015). It was
reported that the level of Lactobacillus plantarum was elevated in the
pigs who were fed with AXOS (Niewold, Schroyen, Geens, Verhelst, &
Courtin, 2012). The increase of Lactobacillus plantarum was related to
the increase of pancreatitis-associated protein, an antimicrobial protein,
which was important in innate immune responses in acute E. coli
challenge (Niewold et al., 2012). Similarly, the activity of the intestinal
alkaline phosphatase increased which was related to the stimulation of
lactobacillus in the distal colonic mucosa of the AXs-fed mice. Intestinal
alkaline phosphatase was able to detoxify lipopolysaccharide and pre-
vent bacterial invasion across the gut mucosal barrier (Chen et al.,
2015). AXs could reduce the adhesion of E. coli through competitive
rejection via stimulated Latic bacteria (Hermes, Manzanilla, Martin-
Orue, Perez, & Klasing, 2011). The results demonstrate that AXs sup-
plementation promotes making an unfavourable environment towards
pathogen (Fu et al., 2011), which prevents further infection of patho-
gens and therefore enhances the immune response. An additional study
shown that rice bran could increase the colonization of Lactobacillus
which might due to elevated mucosal IgA response (Henderson, Kumar,
Barnett, Dow, & Ryan, 2012). The exact effect of AXs supplementation
on IgA response, however, is still not clear. Furthermore, several studies
showed that AXs supplementation was beneficial to increase and
modulate mucus production (Chen et al., 2015). In the mean time, it is
believed that the decrease in mucus thickness related to microbiota
activity would increase pathogen susceptibility (Desai et al., 2016). A
fibrous diet containing AXs protects the mucus barrier and protein
barrier factors through increasing goblet cells and stimulating the
growth of Lactobacillus or Bifidobacteria in the midcolon (Chen et al.,
2015). Goblet cells synthesize and secret several mucins and protein
barrier factors (Chen et al., 2015). The amount of mucin-degrading
Akkermanis muciniphila decreases in cecal in AXs supplementation
feeding group (Van den Abbeele et al., 2011). Moreover, consumption
of the AXs-rich diet upregulates butyrate production leading to a bigger
crypt depth, an indicator of enhancement of intestinal barrier function
(Chen et al., 2015). Likewise, higher butyrate can upregulate the ex-
pression of tight junction proteins, claudin 3 and elevate the production
of mucins, such as the dominant colonic mucin2 (Brahe, Astrup, &
Larsen, 2013; Neyrinck et al., 2011). Meanwhile, it is also possible that
butyrate reduces intestinal permeability through a GLP-2 trophic effect
in the intestinal epithelium (Brahe et al., 2013). AXs modulate dis-
ordered Cl- secretion in the mucosal epithelia to prevent excessive
water secretion, leading to a lower occurrence of pathophysiologic
disease (Chen et al., 2015). AXs supplementation can also lower the
possibility of inflammation in the intestinal. It was reported that SCFAs,
especially butyrate, bound and stimulated nuclear transcription factor
peroxisomeproliferator-activated receptor gamma, reduced the pro-in-
flammatory nuclear transcription factor NFkβ by antagonizing its signal
transduction (Nielsen, Theil, Purup, Norskov, & Bach Knudsen, 2015).
AXOS supplementation also triggers a higher level of IL-10 in the serum
to perform the anti-inflammatory effect.
Since AXs have been shown to modulate immune responses, it is
reasonable to speculate that they may function by acting like pathogen-
associated molecular (Zhang, Li, et al., 2015). This hypothesis was
confirmed by the notable immune-enhancing function of rice bran and
corn husk derived AXs which resemble bacterial lipopolysaccharide in
terms of structure and MW (Zhang, Li, et al., 2015). This indicated that
the structure of AXs including chemical composition affected their
immune-enhancing function. Both AXs from banana peel hemicellulose
and from corn hull contained galactose or glucuronic acid, which led to
strong immune responses (Ogawa et al., 2005; Zhang et al., 2004). It
Z. Chen et al. Journal of Functional Foods 54 (2019) 536–551

avDP, average degree of polymerization; avDS, average degree of substitution; Ara/Xyl Ratio, arabinose/xylose ratio; MW, molecular weight; avDAS, average degree of arabinose substitution; AX, arabinoxylan; AXOS,
has been reported that the AXs contained galactose have the structural

(Malunga and Beta,

features that mainly affect CR3-expressing cells (Zhang, Li, et al., 2015).

(Ayala-Soto et al.,

(Ayala-Soto et al.,
(Bijalwan et al.,
(Malunga et al.,

(Snelders et al.,
(Yuwang et al.,
Comparing AXs from wheat with that from barley, the latter had a
lower MW and showed lower immunological responses in vitro, sug-
Reference

2018) gesting that MW may influenced the immune-enhancing function (Cao

2017)

2016)

2014)

2015)

2013)
2015)
et al., 2011; Samuelsen et al., 2011). It is reasonable to predict that
higher MW AXs have a greater chance to interact with different kinds of
receptors and their biological activity can last longer because higher
In vivo/in

In vitro

In vitro

In vitro

In vitro

In vitro

In vitro

In vitro
MW AXs requires a longer time to be degraded in mammalian systems
vitro

(Zhang, Li, et al., 2015). Other structural features, however, may offset
the effects of MW. Zhou et al. (2010) investigated the immune-enhan-
reducing ability; AXs with lower FA content exert higher toxicity against HepG2 than AXs

AXs with highest FA content shown highest antioxidant ability; AXs with low content of FA
but high content of uronic acid exhibited higher antioxidant ability than AX with medium
AXs with higher content of FA residues had higher antioxidant capacity; monosubstituted

AXs with highest total phenolic content possessed highest antioxidant ability followed by

cing function of AXA and AXE. The MW of AXA was 3.517 × 105 Da

Compared with free FA, bound FA residues demonstrate lower antioxidant capacity.The
AXs with highest branch exert lowest antioxidant effect; tannins contained AXs exhibit
AXs with higher FA content exhibited higher DPPH radical scavenging and ferric iron

without FA content, while the MW of AXE was 3.252 × 104 Da with

When DS and esterified FA content were relatively similar, the antioxidant capacity
declined with decreased DP.DS exerts negative effect on antioxidant capacity of AX

appearance of oxidative gelation lowers antioxidant capacity of feruloylated AXs.

high amount of FA (43.5 mg/100 g). The result turned out to be that
although AXA had higher MW than AXE, AXE stimulated a bigger
macrophage phagocytosis and delayed hypersensitivity reaction than
xylose residues relative proportions influenced the antioxidant capacity

AXA. It was possibly because the relatively higher amount of FA in AXE

allowed more cross-linkages between adjacent AXs chains thereby ex-
hibited a different tertiary conformation which might be easier to be
recognized by the receptors (Zhou et al., 2010). Similarly, Ma et al.
(2016) compared 3 types of water extractable AXs (WEAX) with dif-
ferent MW and FA content, they observed that the immunomodulatory
activity might be related to their content of FA more due to the anti-
AXs with second highest dehydrotri FA content.

oxidant activity and effect of prebiotic of FA. Moreover, AXs from

barley or from the green leaves of Litsea glutinosa had similar MW, but
the latter exerted a higher immunological response (Das et al., 2013;
Samuelsen et al., 2011). In AXs from barley, the arabinose residues
responsible for branching at backbone were either β- or α-anomer while
Effect on antioxidant capacity

highest antioxidant capacity.

in AXs from the green leaves of Litsea glutinosa, the arabinose residues,
responsible for branching at backbone were a mixture of β- and α-
with high FA content

anomers. This indicated that the difference of immune-enhancing

function between AXs from barley and from the green leaves of Litsea
glutinosa might due to different types of branching (Das et al., 2013). It
FA content.

has been widely known that MGN-3 has an extremely high immune-
enhancing function. The mechanisms underlying the im-
munomodulatory effect of MGN-3 is not clear yet, but one hypothesis is
that the structure of MGN-3 has some similarities with lipopoly-
AX1 (Ara/Xyl ratio, 0.53; highest total phenolic content and dehydrotri FA content) AX2
content of FA) AX3 (Ara/Xyl ratio, 1.09, lowest content of FA; higher content of uronic
AX1 (Ara/Xyl ratio, 0.85; high FA content) AX2 (Ara/Xyl ratio, 0.56; low FA content)
AX1 (Ara/Xyl ratio, 0.29; MW, 57 900 gmol−1; high FA content) AX2 (Ara/Xyl ratio,

AX1 (high bound FA content; avDP = 6.6; avDAS = 0.38) AX2 (high free FA content;
AX1 (Ara/Xyl ratio, 1.14; contained tannins) AX2 (Ara/Xyl ratio, 1.41) AX3 (Ara/Xyl
0.30; MW, 41,400 gmol−1; highest FA content) AX3 (Ara/Xyl ratio, 0.54; MW, 1520

(Ara/Xyl ratio, 0.5; second highest total phenolic content) AX3 (Ara/Xyl ratio, 0.55;

saccharide produced by gram-negative bacteria (Zhang, Li, et al.,

AX1 (Ara/Xyl ratio, 0.42; highest content of FA) AX2 (Ara/Xyl ratio, 0.59; medium

16 fractions of AXOS was collected with Ara/Xyl ratio ranged from 0.22 to 0.57

2015). Zheng et al. (2012) treated rats with MGN-3 or its low molecular
weighr hydrolysate (lower than 400 Da), then measured their hepato-
avDP = 6.6; avDAS = 0.39) AX3 (crosslinked; avDP = 3.8; avDAS = 0.23)

protective effect. The MGN-3 low molecular weighr hydrolysate had a

higher protective effect on D-GalN-induced hepatitis by reducing the IL-
lowest total phenolic content; second highest dehydrotriFA content)

8 concentration and its mRNA expression level, the effect compounds in

MGN-3 seemed to have low molecular weight. Zhang, Li, et al. (2015)
assumed that only when un-digestible AXs are degraded into smaller
molecules, can they easily pass through the intestinal wall and went
into the bloodstream. They are then transported to the lymph nodes to
Antioxidant capacity of AXs with different structural features.

exert the effect (Zhang, Li, et al., 2015).

In summary, the structural features of AXs relates to immune
function include MW, sugar composition, the existence of FA as well as
the type of branching. Higher molecule weight of AXs results in more
complicated tertiary structures of AXs, leading to an increase in the
arabinoxylooligosaccharides; FA, ferulic acid.

specific structural features which are able to interact with the receptors.
FA content will change the tertiary conformation through its cross-
gmol−1; low FA content)

linkage, which also contributes to immune modulation function. Above

Molecular structure

all, tertiary conformation characteristics play a significant role in AX’s

immune-enhancing function. Döring et al. (2016) showed that DS
ratio, 1.08)

would change the tertiary conformation of AXs, thus it can be hy-

pothesized that DS may be a contributor to modulate the immune re-
acid)

sponse. However, tertiary structure of AXs is not stable, it will change

because of intestinal environment. Likewise, body digesition and gut
Wheat aleurone

microbiota fermentation will break the tertiary structure. Thus, it is

Sorghum bran
Indian millet
Wheat bran

Wheat bran

worthwhile to figure out how much will the structure remain when AXs
Maize fiber
Rice bran
Sources

are degraded in intestine. FA, regarded as an important content in AXs,

Table 4

contributes to many physiological functions. Nevertheless, there are

only few studies focus on the effect of FA on the immune system.

545
Z. Chen et al.
Researches has been reported that phenolic acids such as flavonoids
were able to scavenge free radicals, thereby inhibit oxidative DNA
damage in lymphocytes, which may be one of the mechanism of the
effect of FA on the immune system (Park, Lee, Jeon, Jung, & Kang,
2010).
5.4. Antioxidant capacity of AXs
Recent studies reveal that the molecular structure, especially DS and
the MW, has a strong correlation with the antioxidant potential of AXs
(Table 4) (Bijalwan, Ali, Kesarwani, Yadav, & Mazumder, 2016;
Malunga & Beta, 2015a; Malunga & Beta, 2015b; Yadav et al., 2017).
As for DS, it has been reported that low branched hydroxycinnamic
acid-bound arabinoxylans derived from kodo millet had a stronger
antioxidant effect compared to hydroxycinnamic acid-bound arabi-
noxylans derived from other sources which had a relatively higher DS
(Bijalwan et al., 2016). Likewise, a strong negative correlation between
DS and antioxidant capability was discovered in AXOS (Malunga &
Beta, 2015a). Both results suggested that the lower content of DS in
AXs, the stronger antioxidant capability. Researchers identify that the
un-substituted xylose at O-2 or/and O-3 in AXs donated a hydrogen or
an electron to participate in the antioxidant reaction (Malunga and
Beta, 2015a, 2016). Likewise, low DS increases the specific functional
groups of xylan with metal-binding activity (for example, –COOH and
–OH) which are the most efficient inhibitors of hydroxyl radical, be-
cause metal ions can be the catalysts in hydroxyl radical production
(Rivas, Conde, Moure, Dominguez, & Parajo, 2013). Nevertheless,
Malunga et al. (2017) found out that WEAX from wheat with higher DS
had a higher antioxidant activity. The WEAX fractions with higher DS
was easier to disperse into the reaction mixture because the steric
hindrance caused by the presence of mono- or di-substituted xylose
prevented intermolecular cross-linking, leading to better participation
of AXs in the redox reaction systems (Malunga et al., 2017).
Several experiments have been done to investigate the effects of the
MW of AXs on their antioxidant properties. Rao and Muralikrishna
(2006) reported that feruloylated AXs with higher MW also had a
higher antioxidant capacity. It was also observed that when the content
of DS was similar to the content of esterified FA in AXs, the antioxidant
capacity declined with decreased DP (Malunga & Beta, 2015a). Ele-
vated (1–4)-β-D-xylopyranose linkages (in the case of increased DP)
lead to a higher amount of unsubstituted xylose, which can participate
in antioxidant reaction through donating a hydrogen or an electron and
thereby increase the potency of AXs and AXOS to against free radicals.
In contrast, Malunga et al. (2017) treated the WEAX fractions with
endoxylanase to reduce their MWs. The results indicated that partial
depolymerization of WEAX doubled their antioxidant activity, which
could be attributed to their higher mobility in the solution and conse-
quently enhanced the radical-scavenging activity (Malunga et al.,
2017). Additionally, the pattern of arabinose substitution and the ex-
istence of acetyl and uronyl groups may also influence the antioxidant
activity of AXs (Malunga et al., 2017; Rivas et al., 2013).
To make a conclusion, researches shows that the effect of DS and
MW on AXs antioxidant ability are inconsistent. It is because that DS
and the MW of AXs not only influenced the specific functional groups of
AXs but also impacted the interaction between AXs molecules through
steric hindrance as well as between AXs and the solvent. It should take
all into consideration when examing the specifical effects of DS and the
MW on the antioxidant capacity of AXs.
The antioxidant capacity correlates with the total phenolic content
of each AX fraction (Bijalwan et al., 2016; Malunga & Beta, 2015b;
Yuwang et al., 2018). The phenolic acid of AXs mostly is covalently
bounded to arabinose residue, generally including a large amount of
FA, some p-coumaric acid, and a little caffeic acid. Some special kinds
of AXs also have phytic acid, tannin, and anthocyanins (Aguedo,
Fougnies, Dermience, & Richel, 2014; Ayala-Soto et al., 2015; Bijalwan
et al., 2016; Malunga et al., 2016; Revanappa & Salimath, 2011; Rosa,
546
Journal of Functional Foods 54 (2019) 536–551
Barron, Gaiani, Dufour, & Micard, 2013).
Among the total phenolic acid of AXs, FA plays a significant role in
its antioxidant capacity. It has been proposed that FA content was the
major factor determining the antioxidant capacity of feruloylated AXOS
(Malunga et al., 2017). Additionally, among FA, di-FA and tri-FA, all
esterified to arabinose, tri-FA had a higher antioxidant capacity since
more units of FAs in each molecular elevated the hydrogen donor ca-
pacity of the moiety through providing more –OH groups (Ayala-Soto,
Serna-Saldívar, García-Lara, & Pérez-Carrillo, 2014). As for the inter-
molecular reaction between feruloylated AXs, Snelders et al. (2013)
observed a reduction of the antioxidant capacity and formation of
oxidative gelation, probably attributed to dimerization of the FA moi-
eties. Although oxidative gelation lowered antioxidant capacity of fer-
uloylated AXs, it, however, enhanced the viscosity and improved some
other physiological functions (Aguedo et al., 2014).
Comparing with free FA, bound FA residues demonstrate a different
antioxidant capability due to the interaction between FA and AX moi-
eties. FA which is esterified to AXs changes feruloylated AXs solubility,
which will influence the antioxidant effect of feruloylated AXs. Several
research groups reported that feruloylated AXs had a higher antioxidant
capability when comparing to the similar amount of free FA. This result
was further confirmed by using ORAC and ABTS antioxidant assays
(performed in aqueous medium) (Malunga et al., 2017). The possible
mechanism is that the hydrophily of FA is increased when FA is ester-
ified to arabinose, which increases the effective concentration of FA in a
water medium. Similarly, in physiological conditions (mostly in aqu-
eous medium), feruloylated AXs have higher antioxidant capacity
(Malunga et al., 2017). When the assays performed in oil-water
medium, the antioxidant effects of feruloylated AXs in the oxidation
system of LDL and lipid were higher compared to free FA (Ayala-Soto
et al., 2014; Snelders et al., 2014). It is because esterified FA provided a
lipophilic part to hydrophilic AXs, facilitated their interaction with
oxidant factors located in the interface or in the oil phase. In vivo ex-
periments demonstrated that during interaction with microbiota, the
FA esterase activity in the inoculum was hindered by the presence of
bound FA through steric hindrance, thus, less FA was released during
incubation (Snelders et al., 2014). Free FA was further metabolized into
less antioxidative 4-vinylguaiacol and 3-phenylpropionic (Snelders
et al., 2014). Therefore, in the colon, bound FA can prevent it from
being destructed by gut microbiota because of its molecular and special
microstructure, results in a sustained antioxidant capacity (Snelders
et al., 2014). In contrast, Rivas et al. (2013) found that compared with
free FA, the ability of ferulated AXs to protect β-carotene-linoleic
emulsions from oxidation was lower. It is because feruloylated oligo-
saccharides are more hydrophilic compared to free FA, which will
hinder their interaction with the oil-water interface in the emulsion,
thus reduces the emulsifying capacity. Lower emulsifying capacity ne-
gatively affects the partition coefficient between the aqueous and the
lipophilic phase, which is reported to affect its antioxidant capacity
(Snelders et al., 2013). Similarly, the viability of HepG2 cells and their
IC50 after treatment with AXs fractions showed that feruloylated AXs
containing mostly free FA exhibited higher hydrophobicity, and might
be deeply embedded in membranes (oil medium). Therefore they could
break oxidative chain reaction and exhibited high antioxidant capacity
(Oteiza, Erlejman, Verstraeten, Keen, & Fraga, 2005; Yuwang et al.,
2018).
It can be concluded that the feruloylated AXs demonstrates incon-
sistent antioxidant capacity in water, oil-water and oil medium re-
spectively. The different solubility of feruloylated AXs in each medium
can be one of the reasons. Thus, to exam the antioxidant capacity of
feruloylated AXs under physiological condition, the solubility of fer-
uloylated AXs in different systems is of great importance to investigate.
Moreover, AXs with high free FA content leading to high solubility in
oil medium should be put into consideration, for it may be deeply
embedded in the membrane to effectively perform an antioxidant
ability. The molecular and tertiary conformation of feruloylated AXs
Z. Chen et al.
will hinder the structural transformation during gut microbiota fer-
mentation and consequently improve the antioxidant availability in the
colon. In the colon, FA in bound or free form, without being degraded
by gut microbiota, can directly exert high antioxidant ability on colon
epithelium cells, thereby may be able to decrease colorectal cancer
(Snelders et al., 2014). At the same time, the structure of saccharide
moiety of feruloylated AXs was observed to change the bioavailability
in plasma. When rats fed with free FA, the concentration of FA present
in plasma in the free and conjugated forms was higher but for a shorter
time compared with rats fed with bound FA (Zhaohui, Yukari, & Hiroo,
2003). Thus, when to determine the antioxidant capacity of fer-
uloylated AXs, we should take not simply its FA content into con-
sideration, but also the solubility, MW as well as special tertiary con-
formation. Since the bound FA content and free FA content of
feruloylated AXs influence antioxidant capacity differently, further
studies should be performed to study the balance between bound FA
and free FA content to obtain specific feruloylated AXs with highest
antioxidant capacity in physiological condition.
Generally, the p-coumaric acid content in AXs is the second highest
phenolic acid followed by FA in AXs (Yuwang et al., 2018). Ayala-Soto
et al. (2014) even showed that p-coumaric exerted a higher antioxidant
capacity compared to the same amount of FA. High tannin sorghum
brans containing high tannin and nine 3-deoxyanthocyanins are known
to have higher antioxidant properties than other phenols and are cur-
rently being considered as effective nutraceuticals against oxidative
stress (Ayala-Soto et al., 2015). AXs from destarched wheat bran con-
tain a high amount of phytic acid. Although phytic acid is a chelator of
several minerals of nutritional importance, resulting in a decrease in
minerals bioavailability and dietary deficiencies, it can be a source of
phosphate and is thought to be anti-carcinogenic thanks to its anti-
oxidant properties (Aguedo et al., 2014). Further research shall be able
to find out the exact contribution of phytic acid in AXs to human health.
Above all, both the content of total phenolic acid and AXs structure
contribute to the antioxidant capacity of feruloylated AXs. Compared
the two factors, the antioxidant capacity of feruloylated AXs was mainly
dependent on FA content, regardless of bound FA or free FA. However,
the role of AXs moiety of feruloylated AXs in antioxidant capacity
shouldn’t be underestimated. We hypothesized that the hydroxyl groups
of unsubstituded xylose AXs moiety may participate in antioxidant re-
action, and AXs moiety may the influence the antioxidant ability of FA.
Both of them may be the mechnisms of AXs moiety ability to change the
antioxidant ability of feruloylated. So far, there are plenty of studies
focus on the antioxidant ability of AXs, however, most studies con-
ducted in vitro and the antioxidant effects of feruloylated AXs in vivo
are still unclear. Further studies may need to focus on the degradation
of feruloylated AXs in intestine and determine the antioxidant effect in
vivo, since digestion and interaction with gut microbiota exert large
effects on feruloylated AXs antioxidant capacity.
6. The relationship between structure and physiological functions
Different AXs structure exert different physiological function
(Fig. 3). It can be concluded that AXs with lower molecule weight,
lower DS, less FA content and simple linkage, and sugar pattern lead to
a higher fermentation rate and SCFA production. Comparing with AXs,
AXOS tends to stimulate the growth of bifidobacteria. When it comes to
lipids metabolism and glucose metabolism, the viscosity related struc-
tures are more important which including MW, arabinose: xylose ratio,
the degree of branching and the content of bound FA. AXs with higher
MW, the degree of branching and bound FA content will cause higher
viscosity. However, AXs with lower or higher viscosity both have some
benefits to human. As for immune-enhancing function, AXs with higher
MW, higher content of FA or inclusion of galactose or glucuronic acid
can strongly enhance immune function. The spatial arrangement of AXs
plays an important role in the immune-enhancing function. Moreover,
emulsifying capacity, solubility, and the amount of antioxidant
547
Journal of Functional Foods 54 (2019) 536–551
functional group exert a remarkable impact on the antioxidant capacity,
which correlates with DS, MW and content of total phenolic acid
especially FA. The relationship between antioxidant capacity and each
structural feature should not be analyzed separately, but rather should
all be taken into consideration. In addition, because AX’s antioxidant
ability would be greatly influenced by the surrounding medium, the
antioxidant availability in physiological conditions is of great im-
portance. Overall, among all the structural features of AXs, molecule
weight, DS and FA content remarkably influence their physiological
functions in a complex way.
FA is of great significance in the physiological functions of AXs
especially in AXs’ antioxidant capacity. Likewise, it exhibits a cross-
linking effect to highly improve the viscosity of AXs, which is able to
modulate lipid and glucose metabolism. However, up to now, the in-
formation is not enough to compare the contribution of FA content and
AX moiety in feruloylated AXs on physiological functions. There are
only few studies concentrate on the ability of FA to change composition
and abundance of gut microbiota. The contribution of FA on modula-
tion of immune system is still not clear. Furthermore, it has been re-
ported FA would distribute to bloodstream or to peripheral tissue after
absorption, and it is possible that the FA distributed to different part of
the body results in different health benefits. At the same time, the
structure of saccharide moiety of feruloylated AXs was observed to
change the bioavailability in plasma as well as in colon which may
change the physiological functions of AXs. Further studies may need to
find out the structure of saccharide which in favor of bioavailability of
FA.
7. Conclusion
Above all, the interaction between AXs and gut microbiota changes
SCFAs production as well as the composition and abundance of colonic
microbiota, both impact human health. At the same time, AXs de-
monstrated various physiological functions. However, the specific in-
fluence on each physiological functions need to be improve by further
researches. As for the effects on lipid and glucose metabolism, there are
lack of studies to investigate the effects of AXs themselves on the me-
tabolism, including the mechanism of AXs to change the gene expres-
sion. Likewise, the antioxidant capacity under inner environment of
human body is still unclear. When it comes to the direct effect of AXs on
physiological functions, it is important to find out the bioactive fraction
of AXs. However, there are few studies focus on this fraction. It has been
reported the immunoregulation effect compounds in MGN-3 seemed to
have low molecular weight (lower than 400 Da). Thus, it may be hy-
pothesised that the bioactive fractions which have the ability to mod-
ulate the gene expression in liver or absorped into plasma may have the
similar molecular weight as the effect compounds in MGN-3. AX’s
structural characteristics have a big impact on those physiological
functions and interaction with gut microbiota. Molecule weight, DS,
and FA content are three main factors influence their physiological
functions. The structure characteristics can be one of the factors to
analyze physiological functions of different kinds of AXs from various
sources or extracted by diverse methods. Future researches can design
particular method to obtain AXs with specific structure in order to ac-
quire products for health-improving or for food application.
8. Declaration
The author declares no conflict of interest.
9. Ethics statements
This research did not include any human subjects and animal ex-
periments.
Z. Chen et al. Journal of Functional Foods 54 (2019) 536–551

Viscosity
Solubility
Immune-enhancing ability Lipid and glucose metabolism Viscosity
The amount of SCFAs The amount of SCFA The amount of SCFA
Antioxidant capacity Lipid and glucose metabolism
Antioxidant capacity
substitution Immune-enhancing ability

Glca D-Gal α-L-Ara α-L-Ara

Xyl - Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl – Xyl –Xyl – Xyl
β-L-Ara - α-L-Ara - α-L-Ara α-L-Ara Gal – Ara
Type of O Substitution
branching pattern

The amount of SCFAs The amount of SCFA

Immune-enhancing ability Antioxidant capacity

Viscosity
Solubility
The amount of SCFA
Lipid and glucose metabolism
Antioxidant capability
Immune-enhancing ability
Fig. 3. Overall representation of different impacts on physiological functions of each AX structural features. MW, FA content and substitution (including ara/xyl
ratio, degree of substitution) are the three main factors affecting physiological functions, exerting effects on all physiological functions and physicochemical
properties mentioned in this article. Special sugar composition such as galactose and glucuronic impacts AX immune-enhancing ability and the amount of produced
SCFAs, similar as the effects of type of branching. At the same time, AX substitution pattern (including different substitution site) change the amount of produced
SCFAs and its antioxidant capacity.

Acknowledgment
This work was supported by Sichuan Science and Technology
Program (Grant No. 2018JY0472), the State Key Program of National
Natural Science of China (Grant No. C170105) and Scientific Research
Training Program for Undergraduates of Sichuan Agricultural
University (Grant No. 2019529).
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