Food Chemistry xxx (xxxx) xxxx

Contents lists available at ScienceDirect

Food Chemistry
journal homepage: www.elsevier.com/locate/foodchem

Review

Prebiotic mannooligosaccharides: Synthesis, characterization and bioactive

properties
Uttam Kumar Jana, Rahul Kumar Suryawanshi, Bhanu Pratap Prajapati, Naveen Kango
⁎

Department of Microbiology, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, MP 470003, India

ARTICLE INFO ABSTRACT

Keywords: Functional oligosaccharides are non-digestible food ingredients that confer numerous health benefits. Among
Mannooligosaccharide these, mannooligosaccharides (MOS) are emerging prebiotics that have characteristic potential bio-active
Prebiotic properties. Microbial mannanases can be used to break down mannan rich agro-residues to yield MOS. Various
Probiotic applications of MOS as health promoting functional food ingredient may open up newer opportunities in food
Mannan
and feed industry. Enzymatic hydrolysis is the widely preferred method over chemical hydrolysis for MOS
Mannanase
production. Presently, commercial MOS is being derived from yeast cell wall mannan and is widely used as
Nutraceutical
Anticancer prebiotic in feed supplements for poultry and aquaculture. Apart from stimulating the growth of probiotic mi­
Microflora croflora, MOS impart anticancer and immunomodulatory effects by inducing different gene markers in colon
cells. This review summarizes recent developments and future prospects of enzymatic synthesis of MOS from
various mannans, their structural characteristics and their potential health benefits.

1. Introduction juice, resistance to gastrointestinal (GI) enzymes, non-absorption in

Health promotion by dietary modulation of the intestinal microflora
through consumption of functional foods is the recent spurt of interest
in the area of dietetics. Use of prebiotics is being construed as a better
way of managing health issues through directed intonation of the gut
microbiota. Alarming emergence of multidrug resistance in humans and
animals is a compelling reason behind avoidance of antibiotics.
Prebiotic substrates get selectively fermented by beneficial micro­
organisms in the gut and confer numerous health benefits to the host
(Gibson et al., 2017). Prebiotics, thus, enrich health promoting gut
microbiota, thereby imparting anti-obesity, anti-neoplastic, anti-al­
lergic, hypocholesterolemic and immunomodulatory effects to the host.
Important characteristics of prebiotics include acid stability in gastric
upper GI tract and selective enrichment of probiotic gut microbiome
(Aachary & Prapulla, 2010; Macfarlane, Macfarlane, & Cummings,
2006). A variety of functional oligosaccharides such as fructooligo­
saccharides (FOS), xylooligosaccharides (XOS), galactooligosaccharides
(GOS), inulooligosaccharides (IOS) and mannooligosaccharides (MOS)
are being explored worldwide as a possible intervention in health sector
(Srivastava, Panwar, Prashanth, & Kapoor, 2017). Among these, FOS
(Kestose GF2 and Nystose GF3) have acquired special status with global
production amounting to 134 kilo tons in 2015 (https://www.grand­
viewresearch.com/industry-analysis/fructooligosaccharides-market).
At the same time, other oligosaccharides, such as XOS and MOS, are
being explored at a faster pace than ever. Although the use of coffee
powder in health promotion was previously reported, Asano et al.

Abbreviations: MOS, mannooligosaccharide; SCC, short-chain carbohydrate; GI, gastrointestinal; XOS, xylooligosaccharide; DP, degree of polymerization; dfCM,
defatted copra meal; PKC, palm kernel cake; LBG, locust bean gum; GG, guar glactomannan; KG, konjac glucomannan; CM, copra meal; FACE, fluorescence assisted
carbohydrate electrophoresis; HPLC, high-performance liquid chromatography; M1/Mn, mannose; M2, mannobiose; M3, mannotriose; M4, mannotetraose; M5,
mannopentose; M6, mannohexose; GH, glycoside hydrolases; FPLC, fast protein liquid chromatography; NMR, nuclear magnetic resonance; GC–MS, gas chroma­
tography-mass spectrometry; TGA, thermogravimetric analysis; DTA, differential thermal analysis; SCFA, short-chain fatty acids; TLC, thin layer chromatography;
GLC-FID, gas-liquid chromatography-flame ionization detector; CE-LIF, capillary electrophoresis-laser-induced fluorescence; DSC, differential scanning calorimetry;
TLR, toll-like receptor; STAT, signal transducer and activator of transcription; SOD, superoxide dismutase; MDA, malondialdehyde; GSH-Px, selenium, glutathione
peroxidase; HDL, high-density lipoproteins; COX, cyclooxygenase; NDF, neutral detergent fiber; ADF, acid detergent fiber; LFD, low-fat diet; HFD, high-fat diet;
HPAEC-PAD, high-performance anion exchange chromatography with pulsed amperometric detection; ESI-TOF MS, electrospray ionization time-of-flight mass
spectrometer; MALDI-TOF, matrix-assisted laser desorption/ionization time-of-flight
⁎
Corresponding author.
E-mail addresses: uttamjana0975@gmail.com (U.K. Jana), suryawanshi2311@gmail.com (R.K. Suryawanshi), bhanuprajapati55@gmail.com (B.P. Prajapati),
nkango@gmail.com (N. Kango).

https://doi.org/10.1016/j.foodchem.2020.128328
Received 7 March 2020; Received in revised form 8 August 2020; Accepted 5 October 2020
0308-8146/ © 2020 Elsevier Ltd. All rights reserved.

Please cite this article as: Uttam Kumar Jana, et al., Food Chemistry, https://doi.org/10.1016/j.foodchem.2020.128328
U.K. Jana, et al.
(2001) made the first mention of the coffee derived MOS as prebiotics.
Beneficial effects of mannanase (Hemicell®) treatment of feed in poultry
and piggery are well explored and documented, however, the exact
mechanism of MOS functionality remains to be deciphered (Pettey,
Carter, Senne, & Shriver, 2002).
Mannans occur as homo- (linear mannan) or hetero-polymers (ga­
lactomannan, glucomannan and galactoglucomannan) in a variety of
plants as either storage or structural components. Mannans consist of
repeating mannose moieties linked with β-1, 4-glycosidic bonds (Soni &
Kango, 2013). Galactomannan is found in the endosperm of different
plant sources such as coconut (Cocos nucifera), guar gum (Cyamopsis
tetragonoloba) and tara gum (Caesalpinia spinosa) while glucomannan
occurs in the tubers of konjac (Amorphophallus konjac) and some orchid
species (Himantoglossum caprinum) (Nopvichai et al., 2019). In food
industry, heteromannans are routinely used as gelling, thickening or
stabilizing agents. MOS are short chain carbohydrates consisting of
3–10 mannose residues (Gomez, Miguez, Yanez, & Alonso, 2017).
Currently, MOS are produced by enzymatic, alkaline or acidic hydro­
lysis of cell wall mannans derived from yeast (Saccharomyces cerevisiae)
or plant galactomannans (Kalidas et al., 2017; Prajapati, Suryawanshi,
Agrawal, Ghosh, & Kango, 2018). MOS, consisting of linear chains of
mannose, can further be classified as α- and β-MOS. The difference
between α- and β-MOS is based on the glycosidic linkage present in the
parent mannan polymer. α-MOS are derived from hydrolysis of α-1, 6-
mannan present in the yeast cell wall, whereas β-MOS are obtained
from plant mannans linked by β-1, 4-glycosidic bonds. Commercial
preparations, such as SAF-mannan®, Bio-Mos® and Active MOS® con­
sisting of α-MOS derived from the yeast, are largely employed as pre­
biotics in the poultry industry. MOS are generated by the hydrolytic
cleavage of different naturally occurring mannans that results in the
release of β-MOS of varying degree of polymerization (DP) (Singh,
Ghosh, & Goyal, 2017; Titapoka, Keawsompong, Haltrich, &
Nitisinprasert, 2007). Recent developments suggest that MOS may play
a pivotal role as functional food ingredient and may prove to be a
significant intervention as an antioxidant and anti-cancer agent (Ghosh,
Verma, Tingirikari, Shukla, & Goyal, 2015; Jana & Kango, 2020).
In this review, we have focused on the recent developments in
chemical and biocatalytic MOS production from different mannans,
purification strategies and applications thereof. An elaborate account of
structural characteristics and various aspects of prebiotic functional
effects of MOS are also provided.
2. MOS production
Small amounts of MOS can be isolated from structural and storage
parts of plants as naturally occurring constituents. Additionally, to meet
high demand and make the preparation cost-effective, MOS can be
derived either by chemical or enzymatic hydrolysis of different man­
nans and mannan-rich agro-industrial wastes. Various mannan-rich
substrates may be subjected to controlled enzymatic, chemical or hy­
drothermal hydrolysis or a combination of these methods for obtaining
desired MOS (Fig. 1A). At present, commercial preparations consisting
of a mixture α-MOS, β-glucans and mannoproteins, e.g. SAF-mannan®,
are derived from yeast (S. cerevisiae) cell wall through autolysis
(Fowler, Kakani, Haq, Byrd, & Bailey, 2015; https://phileo-lesaf­
fre.com/en/products/yeast-parietal-fraction-safmannan/). Recent de­
velopments in MOS production employing different strategies are given
in Table 1a.
2.1. Chemical and physical methods
Different types of chemical and physical methods such as detergent
treatment, hydrothermal treatment and acid or alkaline hydrolysis have
been used for MOS generation from different mannans. Hydrothermal
treatment and acid hydrolysis are the most commonly employed
methods as mannan is readily degraded to oligomers at high
2
Food Chemistry xxx (xxxx) xxxx
temperatures (Pronyk, Mazza, & Tamaki, 2011). Hydrothermal treat­
ment (180–240 °C for 3–60 min) of guar gum has been shown to release
MOS with DP up to 20 (Miyazawa & Funazukuri, 2006). Physical batch
reactors are pressurized constant volume vessels which are used to
process materials under the specific temperature and pressure (Smith,
Inomata, & Peters, 2013). In case of the physical batch reactor process,
the biomass decomposition is much higher than other reactors due to
large biomass residence time; however, batch reactors have a low re­
covery rate at high temperatures (Yuliansyah, Kumagai, Hirajima, &
Sasaki, 2019). In a report, MOS recovery after mannan hydrolysis in a
batch reactor decreased from 17% at 160 °C to 7% at 220 °C (Nattorp,
Graf, Spuhler, & Renken, 1999). However, in some cases, a combina­
torial approach based on both chemical and physical treatments was
applied for MOS generation. Cypress vine seed gum mannan hydrolysis
with 0.1 N sulfuric acid at 100% microwave for 10 s liberated oligo­
saccharides (Singh, Sethi, Tewari, Srivastava, & Sanghi, 2003). Natu­
rally occurring plant MOS can also be extracted using detergent solu­
tions. Yields upto 16.81% of MOS consisting of DP2 to DP8 residues
were obtained from palm kernel cake (PKC) by neutral detergent so­
lution extraction (Faseleh Jahromi et al., 2016). Beside the use of sul­
furic acid as the chief hydrolysis agent, acetic anhydride and acetic acid
are also used for effective MOS generation. MOS generated after the
hydrolysis of S. cerevisiae cell wall were acetylated using a mixture of
acetic anhydride, acetic acid and concentrated sulfuric acid (Marzaioli,
Bedini, Lanzetta, Parrilli, & De Castro, 2014). Use of alkaline hydrolysis
has also been demonstrated in the release of small DP MOS from
mannans. Treatment of S. cerevisiae cell wall mannan with 0.1 N sodium
hydroxide released DP 3–4 MOS (Nakajima & Ballo, 1974). For product
recovery, chemical methods of MOS extraction require pH neutraliza­
tion or acid or alkali removal and thus there is a possibility of alteration
in the chemical composition of MOS. In the case of physical methods,
there is no such need of neutralization and hence there is less chance of
change in the nature of MOS (Bortoluzzi et al., 2018).
2.2. Enzymatic methods
Endo 1, 4 β-mannanases (EC 3.2.1.78) randomly cleave β-1, 4 gly­
cosidic bonds present in the mannan backbone resulting in generation
of different DP MOS (Suryawanshi, Jana, Prajapati, & Kango, 2019;
Kango et al., 2019). According to the CAZy database, glycosyl hydrolase
(GH) families such as GH 5, 26, 45, 113 and 134 (http://www.ca­
zy.org/Glycoside-Hydrolases.html) are responsible for mannanolytic
activities, wherein GH 45 and 134 show inverting mechanism and
others exhibit retaining mechanism (Fig. 1B). Extracellular mannanases
are produced by different microorganisms like fungi (Jana,
Suryawanshi, Prajapati, Soni, & Kango, 2018; Liao et al., 2014; Shimizu
et al., 2015; Soni, Rawat, Pletschke, & Kango, 2016) and bacteria
(Chauhan, Sharma, Puri, & Gupta, 2014). Physical or chemical pre­
treatments may also be coupled with the enzyme treatment for en­
hancing the degradability of the mannan-rich complex biomass. Re­
moval of lignin content enhances accessibility to the polymer backbone
making it more amenable to the enzymatic hydrolysis (Prajapati, Jana,
Suryawanshi, & Kango, 2020). Elaborate account of MOS generation
using microbial mannanases are provided in the following sections.
2.2.1. MOS generation using bacterial mannanases
Several bacterial species from Bacillus, Streptomyces, Kitasatospora
and Enterococcus genera are known to be active producers of β-man­
nanase. Among these, Bacillus is the most explored for β-mannanase
production. Zhou, Xue, and Ma (2018) reported a thermo-alkaline re­
sistant β-mannanase from alkaliphilic Bacillus clausii which hydrolyzed
different mannans (LBG and KG) and liberated MOS up to DP6. In a
report, MOS (DP 2–6) were generated from dfCM using Bacillus circulans
NT 6.7 β-mannanase (Prayoonthien, Rastall, Kolida, Nitisinprasert, &
Keawsompong, 2019). Thermostable β-mannanases are advantageous
as higher yields of MOS are achieved as the high temperature decreases
U.K. Jana, et al. Food Chemistry xxx (xxxx) xxxx

Locust bean gum Guar gum Palm kernel cake Copra meal

Yeast Plant mannans Mannan-rich Agrowaste

Acid/Alkaline Hydrothermal/ β-mannanase

Autolysis hydrolysis Microwave extraction hydrolysis

3-10 DP α-Mannooligosaccharide (MOS) 3-10 DP β-Mannooligosaccharide (MOS)

B GH-5
(Mechanism: Retaining;
3D structure: (β/α)8 ;
Proton donor: Glutamic
acid)

GH-134 GH-26
(Mechanism: Inverting) (Mechanism: Retaining; 3D
structure: (β/α)8 ; Proton

β-mannanase
donor: Glutamic acid)

GH-113 GH-45
(Mechanism: Retaining; (Mechanism: Inverting;
3D structure: (β/α)8 ; Proton donor: Aspartic
Proton donor: Glutamic acid)
acid)

Fig. 1. (A) Different strategies for the production of mannooligosaccharides (MOS), (B) CAZy families having mannanolytic enzymes for production of MOS.

mannan viscosity and increases the substrate diffusion coefficient (Haki
& Rakshit, 2003). Luo, Miao, Li, Du, and Yu (2017) have reported a
highly thermostable recombinant β-mannanase (stable at 100 °C for
10 min) from thermophilic Bacillus subtilis that hydrolyzed LBG to
mannose (37.46%) and MOS (63.64%). Mutation in bacterial manna­
nase genes may improve the efficacy of enzyme by enhancing catalytic
activity and increasing stability at high temperature and pH. In this
context, Bacillus sp. exposed to X-rays resulted in significant enhance­
ment in β-mannanase activity resulting in higher production of MOS of
DP 3–5 from dfCM (Chaikaew et al., 2016). Apart from using native
bacteria to produce mannanases, robust over-expression platforms can
be used. Nopvichai et al. (2019) cloned β-mannanase of B. subtilis and
utilized it for MOS (DP 2–6) generation by CM hydrolysis for 48 h.
Bacillus sp. SWU60 endo-β-mannanase efficiently released glucosyl
mannobiose and cellobiosyl mannobiose from KG and generated ga­
lactomannan-oligosaccharides (DP 5–8) from LBG (Seesom et al.,
2017). Zang et al. (2015) studied a thermostable β-mannanase from
Bacillus pumilus which efficiently converted LBG into M2, M3, M5 and
high DP MOS into DP3. A GH 113 β-mannanase from thermo-acid­
ophilic Alicyclobacillus sp. showed higher substrate affinity towards
glucomannan over galactomannan and released M2 and M4 as major
products. The presence of galactose side chain in galactomannans
causes steric hindrance to the binding of the enzyme (Xia et al., 2016)
and thus, β-mannanase augmented with α-galactosidase performed
better and released higher amounts of sugars. The accessory α-ga­
lactosidase breaks down the α-1, 6-linked galactose unit in the ga­
lactomannan backbone. The combination of the recombinant β-man­
nanase and α-galactosidase belonging to the mannan gene cluster of
Bacillus sp. liberated high amounts of galactose, M1, M2 and M3 from
galactomannans as compared with β-mannanase hydrolysis alone (Song
et al., 2018). Two different mannanases from Cellvibrio japonicas
(CjMan5A of GH5 & CjMan26A of GH26) have been reported, where
CjMan5A acted upon galactoglucomannan and released high amounts
of DP 3 and 4, whereas CjMan26A released only M1 and M2 because the

3
U.K. Jana, et al. Food Chemistry xxx (xxxx) xxxx

GH26 family mannanases are reported to have higher affinity for M3

(Rungruangsaphakun & Keawsompong,

oligosaccharides (Arnling Baath et al., 2018; Hogg et al., 2003). There
are some noteworthy reports on mannanases from some other bacterial

(Miyazawa & Funazukuri, 2006)

(Faseleh Jahromi et al., 2016) sources. In this context, an alkaline-thermostable mannanase from

(Suryawanshi & Kango, 2020)

Streptomyces sp. was found to release DP 1–3 from LBG (Pradeep et al.,
(Srivastava et al., 2017)
2016). The mannanolytic system of Kitasatospora sp. was used for de­

(Jana & Kango, 2020)

(Pradeep et al., 2016)

(Nattorp et al., 1999)
grading different mannan-rich substrates such as LBG, Ivory nut
(Zhou et al., 2018)
(Jian et al., 2013)

mannan, KG and porang potato which resulting in production of man­

nose and mannooligosaccharides (DP 2–6) (Rahmani et al., 2017). A
Reference

hybrid mannanase from Klebsiella oxytoca hydrolyzed KGM, LBG and

2018)
dfCM and liberated different mannooligomers ranging from DP 2–6
(Pongsapipatana et al., 2016). Exo-mannanase from Bacteroides fragilis
catalyzed hydrolysis of different mannans and produced M2 as the
Identification/quantification

major end product using mannosylglucose phosphorylase mannan

catabolic pathway (Kawaguchi et al., 2014; Senoura et al., 2011).
Chauhan et al. (2014) have described a β-mannanase from Bacillus
nealsonii PN-11 that degraded LBG into MOS (M3, M4 and M5). Re­
HPAEC, HPLC

sponse surface methodology (RSM) is a useful statistical tool that allows

process optimization by assessing the interaction among different in­
method

ESI-MS
HPLC
HPLC

HPLC

HPLC

HPLC

HPLC

dependent parameters and response variables (Astray, Gullon, Labidi, &

TLC

TLC

Gullon, 2016). After optimization of process parameters for dfCM hy­

drolysis with Bacillus circulans NT 6.7 mannanase by RSM, MOS pro­
DfCM: 38.86
LBG: 20.94
MOS yield

CM: 32.25

CM: 38.99
GG: 49.55
KG: 41.35

KG: 66.09
PKC: 9.05
LBG: 7.75

duction reached 14.34 mg/mL with 15% substrate concentration,

16.52 U/mL mannanase dosage and 12 h reaction time
16.81

9.6%
75.2
(%)

30

(Rungruangsaphakun & Keawsompong, 2018). Among bacterial man­

–

–
–

nanase producers, Bacilli are the most prominent producers of ther­

mostable, salt tolerant and pH stable mannanases and are reported to
Degree of Polymerization

generate various DP MOS from mannans.

2.2.2. MOS generation using fungal mannanases

White-rot and brown-rot basidiomycetes such as Trametes versicolor,
Pleurotus ostreatus, Ceriporiopsis subvermispora, Piptoporus and
2–20
(DP)

>4

>4
2–8
2–5
2–5

2–6
2–6

2–6

2–3

Schizophyllum commune, found associated with forest litters, are known

to produce mannanolytic enzymes. Besides these, some Aspergilli are
reported to be excellent producers of β-mannanases (van Zyl, Rose,
Trollope, & Gorgens, 2010). Recently, the Aspergillus quadrilineatus
Thermo-alkaline resistant mannanase from

Mannanase from Aspergillus quadrilineatus

mannanolytic system with prominent endo-β-mannanase activity was

γ-irradiation + endo-β-(1, 4)-mannanase

Mannanase alkaline- thermostable from

utilized for generation of MOS from konjac glucomannan, copra meal

Thermal treatment at 200 °C for 15 s

Mannanase from Aspergillus oryzae

and locust bean galactomannan (Suryawanshi & Kango, 2020). Gen­

Mannanase from Bacillus circulans

eration of MOS (DP 3–7) by hydrolyzing LBG, GG, KG and CM using a

Mannanase from Bacillus sp.

low molecular weight multi-tolerant β-mannanase from Aspergillus or­

Neutral detergent solution

Hydrothermal treatment

yzae was demonstrated. Enzymatically derived MOS were visualized

Production strategy

using highly sensitive fluorescence assisted carbohydrate electrophor­

Streptomyces sp.

esis (FACE) (Jana et al., 2018). β-mannanases belonging to GH5 and

Bacillus clausii

GH113 have been reported to have transglycosylation activity. A GH5

mannanase from Aspergillus nidulans, when incubated with DP4 MOS,
generated high DP transmannosylation products (DP5-7) (Rosengren
et al., 2014). An acido-thermostable β-mannanase from Penicillum ox­
alicum has been demonstrated to produce MOS (DP 2–6) (Liao et al.,
Locust bean galactomannan, Konjac glucomannan, copra meal

2014). Effective bioconversion of steam pretreated PKC by Rhizomucor

Methods of MOS production and their characteristics.

Locust bean galactomannan, Guar galactomannan, Konjac

miehei β-mannanase expressed in Pichia pastoris yielded 261.3 g/kg

Locust bean galactomannan and Konjac glucomannan

MOS (Li, Yi, Liu, Yan, & Jiang, 2018). A cloned thermophilic and
glucomannan, Palm kernel cake and copra meal

acidophilic β-mannanase from Aspergillus kawachii IFO 4308 has been

reported to be very effective in bioconversion of LBG, KG and GG into
short DP MOS at high (10%) substrate concentration (Liu et al., 2020a).
In addition, an endo-β-mannanase sourced from randomly mutagenized
and defatted copra meal (dfCM)

Podospora anserine expressed in Yarrowia lipolytica showed improved

catalytic activity compared to the parental enzyme (Couturier, Feliu,
Locust bean galactomannan

Locust bean galactomannan

Bozonnet, Roussel, & Berrin, 2013). In a study, Aspergillus terreus β-

Mannan (Megazyme Inc.,)

mannanase produced DP3 as predominant oligomer in the case of LBG

Konjac glucomannan

Defatted copra meal

and GG hydrolysis while DP4 was generated from KG (Soni et al.,

Palm kernel cake

2016). Similarly, GH 134 family β-mannanase (Man134A) derived from

Aspergillus nidulans efficiently released DP 2–4 MOS from galactose-free
Guar gum

β-mannan (Shimizu et al., 2015). In an interesting study, Malgas, van

Table 1a

Source

Dyk, and Pletschke (2015) have described synergism between α-ga­

lactosidase and β-mannanase for effective degradation of

4
U.K. Jana, et al.
Table 1b
Different strategies for purification of MOS.
MOS obtained from Substrate Purification step Separation condition
Guar galactomannan Bio-Gel By gravitational pull using a constant flow rate of 9 mL/h
P-2 beads column
Guar galactomannan Bio-Gel By gravitational pull using a constant flow rate of 7.5 mL/h
P-2 beads column
Acetylated galactoglucomannan XBridge Amide column Gradient elution with
(A) 5% acetonitrile + 0.1% formic acid (B) 95% acetonitrile + 0.1% formic acid
Konjac glucomannan Activated carbon column Gradient elution with 15 to 100% ethanol
Locust bean gum
Defatted copra meal Bio-Gel Elution by de-ionized water at 0.2 mL/min flow rate.
P-2 column in FPLC system
P. pinaster wood samples Ultrafiltration and Regenerated cellulose membranes (1–5 kDa cut-off), filtration area of 41.8 × 10-4
nanofiltration m2 at 4 bar pressure
galactomannan. α-galactosidase effectively removed galactose from
both galactomannan and galactose-containing oligosaccharides. Addi­
tion of a linker and carbohydrate-binding module (CBM) in the Tri­
choderma reesei β-mannanase gene significantly improved the bio­
chemical characteristics of β-mannanase and resulted in improved
hydrolysis of cellulose, galactomannan and pretreated sugarcane ba­
gasse (Ma et al., 2017). Among fungal mannanase producers, Aspergillus
spp. are reported to produce copious amounts of multi tolerant MOS-
generating mannases with potential applications.
3. MOS purification
Purification of MOS is important and compelling due to their end
use as a functional food ingredient or a dietary prebiotic. The enzymatic
or physico-chemical hydrolysates and extracts of different mannans
may contain a mixture of different DP MOS and it is possible that other
undesirable sugars as well as non-sugar components may also be pre­
sent. Over the time, different strategies based on size exclusion chro­
matography, membrane filtration, activated charcoal column etc. have
been employed for MOS purification on the lab scale but these are yet to
be explored at the pilot scale (Table 1b). Nowacka-Jechalke et al.
(2018) reported purification of polysaccharide from Cantharellus ci­
barius containing mannose in their backbone using DEAE-52 cellulose
chromatography column and Sephadex G-25 gel filtration column. MOS
obtained from spruce galactoglucomannan were separated by amide
columns with 5% acetonitrile and 0.1% formic acid as mobile phase
(Liu et al., 2018). Sugars are uncharged molecules and thus ion-ex­
change chromatography helps in exclusive removal of charged mate­
rials such as proteins, amino acids and ions from sugar-containing
mixtures or extracts. Size exclusion chromatography with Sephadex (G-
10, G-25) or polyacrylamide (Bio-Gel P2) columns has been extensively
employed for oligosaccharide purification, especially MOS (Jana &
Kango, 2020). In another attempt, oligosaccharides were purified from
KG hydrolysate in three sequential steps including membrane filtration
(0.45 µm), ultra-filtration (cut-off 10 kDa) and finally, elution of oligo
sugars with a linear ethanol gradient (15–100%) through an activated
carbon column equilibrated with water (Seesom et al., 2017). MOS
derived from enzymatically hydrolyzed dfCM were separated using
polyacrylamide bead matrix (Bio-Gel P2, 45–90 µm) using an FPLC
system and eluted with de-ionized water (Ghosh et al., 2015). Pre­
viously, thiopropargyl-mannooligosaccharide mixture was de-acety­
lated and purified using Bio-Gel P-2 columns with water as eluent
(Marzaioli et al., 2014). In another attempt, KG hydrolysate containing
various DP oligosaccharides were separated using different molecular
weight cut-off membranes (103–105 Da) followed by ultra-filtration.
Effective separation was obtained using the 3 × 105 Da cut-off mem­
branes (Jian et al., 2013). In a similar kind of approach, the regenerated
ultra-filtration and nano-filtration cellulose membranes (1–5 kDa cut-
off) were used for MOS purification from auto-hydrolysis liquor of Pinus
pinaster (Rivas, Gullon, Gullon, Alonso, & Parajo, 2012).
5
Food Chemistry xxx (xxxx) xxxx
References
(Jana & Kango, 2020)
(Mary et al., 2019)
(Liu et al., 2018)
(Seesom et al., 2017)
(Ghosh et al., 2015)
(Rivas et al., 2012)
4. Structural characterization of MOS
MOS derived from various mannan-rich sources are characterized
using different methods viz. HPLC for analyzing degree of polymeriza­
tion (Faseleh Jahromi et al., 2016), ESI-TOF MS for deciphering mo­
lecular weight (Albrecht et al., 2011), NMR for verification of the
structure and purity of the compound and HPAEC-PAD for analyzing
MOS constitution (Mn, GluMn or GalMn) (Mikkelson, Maaheimo, &
Hakala, 2013). MOS of different degrees of polymerization from dif­
ferent mannans was separated and quantified by HPLC using a Sugar-
Pak™ Column with RI detector with an oven temperature of 90 °C (Jana
& Kango, 2020). The presence of galactose, glucose and mannose units
in the natural oligosaccharides of Hyptis suaveolens was analyzed using
HPAEC-PAD (Praznik et al., 2017). Furthermore, the analysis of mole­
cular structure of different MOS with different ion mode peaks (either
positive or negative) was evaluated by ESI-MS spectrum where MOS-III
and MOS-IV showed positive and MOS-VI was negative (Kalidas et al.,
2017). ESI-MS was also helpful in studying intact oligosaccharide
structure when present in low concentrations (Cerqueira et al., 2011).
This technique is also useful for studying sugar substitution study, for
example, a (1 → 5) linked β-D-galactofuranose unit linked to manno­
pyranose units and C-6 position was confirmed by ESI-MS (Guo et al.,
2014). Kalidas et al. (2017) confirmed the linear β (1 → 4) manno­
pyranosyl linkage of PKC derived MOS using GC–MS. NMR analysis of
MOS obtained from PKC hydrolysis revealed the α-anomer structure of
MOS-III which was more downfield C/H signal while β-anomer was up
field. In another study, MOS obtained from guar gum and locust bean
gum after treatment with A. oryzae β-mannanase had both α- and β-
anomers while those derived from CM and PKC had only α-anomers
(Jana & Kango, 2020). Another NMR study revealed the presence of two
different DP3 MOS having galactose either at reducing or non-reducing
ends as differentiated by a chemical shift at C6 of D-mannose. The re­
sonance showed at 66.80 ppm in the case of D-galactose attached with
reducing mannose sugar, whereas 66.01 ppm in the case of D-galactose
attached with non-reducing mannose sugar (Mary, Prashanth, Vasu, &
Kapoor, 2019). XRD analysis of MOS revealed that DP2 and DP3 oligos
produced from LBG had a non-crystalline structure and amorphous
nature. In addition, thermal behavior of DP2 and DP5 MOS was ana­
lyzed by TGA and DTA and the final mass loss of DP2 and DP3 was 81%
at 510 and 516 °C, respectively (Srivastava et al., 2017).
5. Health promoting properties of MOS
5.1. Gut microbiota modulation by MOS
The role of probiotics in human as well as animal health promotion
is very well recognized (Martin et al., 2019) and several prebiotic oli­
gosaccharides including MOS are being utilized for modulation of gut
microflora with an aim to enrich probiotic populations (Fig. 2). Dietary
fibers like galactooligosaccharides and fructooligosaccharides were
U.K. Jana, et al.
Intestinal lumen
SCFA
Prebiotics
fermentation
elective
Stimulate selective
Anaerobic
MOS Probiotics gro
growth
Lactobacillus/
Bifidobacteria
epithelium
Intestinal
Lamina propria
TCR
TH2
Dendritic cell
Fig. 2. Schematic presentation of prebiotic health benefits and their bioactive properties in immune-modulation. (TCR: T-cell receptor, SCFA: Short-chain fatty acid).
fermented by the gut microflora into short chain fatty acid (SCFA) such
as acetate, propionate and butyrate while acetate was the major pro­
duct in the case of mannooligosaccharides (De Vadder et al., 2014;
Srivastava et al., 2017). SCFA not only reduce the growth of pathogenic
bacteria by lowering the pH in the gut but also alter the membrane
fluidity and integrity of pathogens because of their partial solubility in
the membrane (Royce, Liu, Stebbins, Hanson, & Jarboe, 2013). The
prebiotic MOS generated from LBG using B. nealsonii mannanase se­
lectively enhanced the growth of Lactobacillus casei and retarded the
growth of the enteropathogen, Salmonella enteric (Chauhan et al.,
2014). MOS-rich mannanase treated PKE (palm kernel extract) sig­
nificantly improved the population of Lactobacillus brevis, Lactobacillus
salivarius and Lactobacillus gallinarum both in vitro and in vivo and
lowered the population of E. coli (Chen et al., 2015). Similarly, MOS
obtained from LBG and dfCM hydrolysates significantly enhanced the
growth of different probiotic Lactobacilli and Weissella confusa JCM
1093 while retarded the growth of E. coli E010 (Pongsapipatana et al.,
2016). On the basis of earlier reports, it could be concluded that MOS
derived either from the mannans (LBG, KG and GG) or mannan-rich
agro-wastes (PKC and CM) share similar potential and can be utilized as
prebiotics. In an interesting study, Mao, Song, Yao, and Wu (2018) have
described the protective effect of physicochemically degraded Konjac
glucomannan on Bifidobacteria against the antibiotics while improving
their biofilm forming ability simultaneously. Similarly, MOS from KG
with high DP oligos were observed to induce the formation of biofilm in
probiotics, Lactobacillus delbrueckii and Lactobacillus acidophilus. In ad­
dition, MOS from LBG promoted production of branched chain amino
acids (BCAA), like leucine, valine and isoleucine (Suryawanshi &
Kango, 2020). Bacillus circulans NT 6.7 mannanase optimally hydro­
lyzed copra meal and generated MOS which effectively promoted the
growth of beneficial gut resident Lactobacilli and Bifidobacteria and
significantly retarded the growth of enteropathogenic Salmonella
Food Chemistry xxx (xxxx) xxxx
E. coli
L. monocytogenes
S. typhi
Reduction in
pathogenic colony
ny
Lower in pH
L
Decrease in colon cancer risk
mineral ion
absorption
Increased
Bacteriocins Defensins
Mast cell
M
Nerve Cell
Eosinophil Neutrophil
Anti-inflammatory, Nerve sensitivity
Anti-allergic
enteritidis S003, E. coli E010, Staphylococcus aureus TISTR 029 and Shi­
gella dysenteriae DMST 1511 (Rungruangsaphakun & Keawsompong,
2018). The incidence of diabetes is increasing globally and is projected
to affect 642 million individuals by 2040 with 90% as type 2 diabetes
patients (Chatterjee, Khunti, & Davies, 2017). In this context, Zheng
et al. (2018) have found impressive results from their in vivo studies on
the effect of MOS on diabetic mice. MOS in combination with an anti-
diabetic drug, metformin (MF), resulted in: (1) enhanced growth of
Allobaculum, which is a butyrate-producing bacteria and an active
glucose utilizer in diabetic mice, (2) synergistic hypoglycemic effects
with decreasing clinical diabetic parameters and repairing islets and
hepatic histology and (3) decline in the methane metabolism, glyco­
lysis/gluconeogenesis metabolism and starch or sucrose metabolism
leading to significant improvement in the health of diabetic mice.
Kalidas et al. (2017) reported isolation of different DP MOS derived
from PKC hydrolysis and found that smaller oligosaccharides or smaller
DP MOS such as DP3 and DP4, effectively enhanced the growth of
Lactobacillus reuteri C1 as compared to the larger DP MOS (> M4). MOS
obtained from LBG hydrolysis were functionally characterized where
DP3 enhanced growth of all the Lactobacilli while DP2 significantly
promoted the growth of all the probiotics, except that of Lactobacillus
helveticus. Also, it is noteworthy that high DP MOS (> 5) did not sup­
port the growth of L. plantarum, L. helveticus, L. casei var. rhamnosus, L.
fermentum, L. acidophilus, or other similar bacteria. In another study,
probiotic strains when grown on DP2, DP3 and DP5 MOS containing
diets, produced acetate as the major SCFA and effectively lowered the
growth of foodborne pathogens such as E. coli, S. typhi and Listeria
monocytogenes (Srivastava et al., 2017). Combined effect of DP2 and
DP3 was evaluated for probiotic strains (Bifidobacterium infantis and L.
acidophilus) as well as non-probiotic enteric bacteria (E. coli and E.
aerogenes) resulting in the enhanced growth of probiotic bacteria with a
change in pH to acidic, presumably due to SCFA production (Ghosh
6
U.K. Jana, et al. Food Chemistry xxx (xxxx) xxxx

Table 2
Effect of MOS on probiotic enrichment and pathogenic deterrence.
MOS source Enriched probiotc Deterred pathogen Reference

Locust bean galactomannan
Palm kernel cake
Locust bean galactomannan and
defatted copra meal
MOS with Metformin (MF)
Palm kernel cake
– Bifidobacterium infantis
Copra meal
Lactobacillus casei
Lactobacillus brevis, Lactobacillus
salivarius, Lactobacillus gallinarum
Lactobacilli, Weissella confusa JCM
1093
Allobaculum
Lactobacillus reuteri C1
Lactobacillus acidophilus
– Salmonella enteritidis S003, Staphylococcus aureus
Salmonella enteric (Chauhan et al., 2014)
– (Chen et al., 2015)
E. coli E010 (Pongsapipatana et al., 2016)
– (Zheng et al., 2018)
S. typhi, Listeria monocytogenes (Srivastava et al., 2017)
E. aerogenes (Ghosh et al., 2015)
(Rungruangsaphakun &
TISTR 029, E. coli E010, Shigella dysenteriae DMST Keawsompong, 2018)
1511

et al., 2015). Similarly, MOS, especially DP2 and DP3, derived from GG
hydrolysis showed significant growth promotion of Lactobacillus spp.
causing simultaneous inhibition of enteropathogens, E. coli and S. typhi
in monoculture and co-culture fermentations (Mary et al., 2019). Var­
ious oligosaccharides such as FOS, GOS, IOS, XOS etc. have also been
explored for Lactobacilli growth promotion and better results were
found with the short DP oligos (Endo, Nakamura, Konishi, Nakagawa, &
Tochio, 2016). It has been concluded from earlier studies that oligo­
saccharides with low molecular weight have higher cellular diffusivity
and molecular mobility (Yang et al., 2008). In an earlier study, Spring,
Wenk, Dawson, and Newman (2000) suggested that MOS might affect
the colonization through blocking bacterial attachment to the gut mu­
cosa. The effect of MOS on the growth of probiotic and pathogenic
organisms are summarized in Table 2.
5.2. Anti-cancer activity of MOS
Colorectal cancer (CRC) is emerging as a common neoplasia
worldwide and its cases are increasing on a regular basis. Consumption
of prebiotic oligosaccharides can be a useful intervention in order to
prevent this lethal disease (Fernandez et al., 2018). Mannose may play
an important role in the prevention of different types of cancers because
mannose and glucose are transported via the same transporter protein
where mannose gets incorporated into the glucose metabolism
(Gonzalez et al., 2018). Besides the mannose hindrance, human CRC
cells continuously expressed Ca2+ ion-dependent specific mannan-
binding proteins (MBP) which were prone to bind the oligosaccharides.
The MBP showed cell cytotoxic activity which is known as MBP-de­
pendent cell-mediated cytotoxicity (MDCC) (Ma et al., 1999). In this
context, only a few studies with MOS have been reported to date and
there are many unexplored areas in this domain of MOS. Ghosh et al.
(2015) have demonstrated 50% cell death of HT29 cells 24 h after
treatment with 500 µg/mL MOS. MOS from agriculture wastes, such as
PKC and CM, were evaluated for different bioactive properties in­
cluding anti-cancer properties. MOS derived from PKC hydrolysis had
ability to decrease the Caco-2 cell viability by 74.19% (Jana & Kango,
2020). Galactomannan fractions from Sesbania cannabina inhibited the
cell growth of different cell lines such as HepG2, MCF-7, A549 and
HeLa cells in a concentration-dependent manner. At 400 μg/mL, these
were very effective at inhibiting A549 cell line and the anti-cancerous
activity increased with the increasing molecular weight (Zhou, Xue
et al., 2018). In contrast, very high molecular weight oligosaccharides
had less effect on the anti-cancerous activity due to their less diffusivity
and molecular mobility, leading to low impact on interaction with
cancer cells (Yang et al., 2008).
5.3. Immunomodulatory activity of MOS
The immunomodulatory functions of galactomannans obtained
from Lupinus luteus seed and dietary yeast have been studied and it was
found that they activated macrophages resulting in the increased pro­
duction of TNF-α in RAW 264.7 cells (Thambiraj, Phillips,
Koyyalamudi, & Reddy, 2018). Therapeutic effects of MOS on the in­
flammatory bowel syndrome (IBS) or Crohn’s disease have been de­
monstrated. MOS can help overcome the dextran sulfate sodium (DSS)
colitis induced clinical symptoms by reducing the expression of pro-
inflammatory cytokines (IL) IL-1a, IL-1b, IL-6, granulocyte colony sti­
mulating factor (G-CSF), KC and MCP-1. MOS directly interact with the
macrophages and trigger production of pro-inflammatory mediators
and also increase the expression of mucin to attenuate harmful bacterial
population (Ferenczi, Szegi, Winkler, Barna, & Kovacs, 2016). In ad­
dition, when MOS was administered in low fat diet-fed male C57BL/6
mice, macrophage number as well as eosinophil count in the mesenteric
white adipose tissue (mWAT) significantly increased but had no im­
mune response related to obesity in high fat diet mice (Hoving et al.,
2018a). In an interesting study, LBG galactomannan stimulated the
production of TNF-α from RAW 264.7 cells and β-hexosaminidase from
RBL-2H3 cells but when LBG was hydrolyzed by thermophilic actino­
mycete Thermobifida fusca BCRC 19214 β-mannanase, it did not elicit
any immunostimulatory activity (Chen et al., 2018). Synthetically de­
rived mannooligosaccharides mimicked the antigenic factor of Candida
and stimulated different cytokines in RAW264.7 macrophages
(Paulovicova et al., 2019). Schematic presentation of prebiotic health
benefits and their role in immune-modulation are illustrated in Fig. 2.
5.4. Other biological effects of MOS
Owing to the wide spectrum of bioactive properties of MOS, they
are believed to play a significant role in improving human health.
Besides being active prebiotics, MOS have been indicated to have an­
tioxidant, anti-inflammatory, cryoprotectant, anti-stress and anti-dia­
betic properties (Fig. 3). MOS fractions from the mushroom, Canthar­
ellus cibarius inhibited COX-1 and COX-2 enzyme activities by 43.86%
and 51.59%, respectively and inhibited proliferation of colon cancer
cells (Nowacka-Jechalke et al., 2018). Intracellular high-mannose-oli­
gosaccharides (HMOS) imparted a cryoprotective effect on the mam­
malian cells. When PC-12 mammalian cells were treated with 1-deox­
ymannojirimycin (α-mannosidase inhibitor) for 72 h, HMOS protected
the cells against freezing injury for > 8-weeks of cryopreservation at
80 °C in 10% (v/v) DMSO solution (Watanabe et al., 2006). MOS de­
rived from coffee mannans have been shown to suppress the blood
pressure in Dahl salt-sensitive (Dahl-S) rats treated with 1.25% salt
(NaCl) solution (Hoshino-Takao et al., 2008). In humans and other
animals a many pathogenic bacteria thrive in the gut which can cause
diseases by binding or adhesion with cells. In this regard, anti-ad­
herence activity against pathogens like Campylobacter jejuni and Cam­
pylobacter coli was observed after administering MOS (up to 40 mg/mL)
with a high-molecular-weight fraction of cranberry extract (up to 3 mg/
mL) on HEp-2 cells (Ramirez-hernandez, Rupnow, & Hutkins, 2015).
The frequency of obesity is increasing drastically and this is emerging as

7
U.K. Jana, et al.
Prebiotic
Immuno-
modulatory Anti-cancer
Manno-
Oligosaccharide
(MOS)
Anti-inflam Anti-
matory diabetic
Anti-oxidant
Fig. 3. Different bio-active properties of MOS.
a global health problem causing chronic diseases such as cardiovascular
problems, type-2 diabetes and hypertension (Liu et al., 2020b). In this
regard, Wang et al. (2018) observed that MOS consumption reduced
body weight gain, lowered serum lipids and reduced insulin resistance
in high-fat diet mouse C57BL/6J. The probable reason behind this effect
was a decrease in the Firmicutes/Bacteroidetes ratio which leads to in­
creased abundance of beneficial probiotic species. In another study,
MOS extracted from coffee have been shown to endorse reduction in
body fat and adipose tissue in overweight individuals when consumed
as part of weight-maintaining diets (St-Onge, Salinardi, Herron-Rubin,
& Black, 2012). MOS decreased the progression of atherosclerosis up to
54% in E3L.CETP mice due to increased fecal butyrate levels and bile
acid levels (Hoving et al., 2018b).
6. MOS in aquaculture
The prebiotic MOS supplementation can enhance the growth of
beneficial gut microbes thus improving the quality of life in animals and
humans by providing several health benefits (Table 3). In case of
aquatic animal culture, most dietary MOS are from feed additives de­
rived from yeast cell wall (S. cerevisiae) which induces growth and
fortifies the immune system (Rungrassamee et al., 2014). Similarly,
MOS supplementation could modulate immune-stimulatory effect by
interaction with a specific receptor in the fish innate immune system
(Iqbal, Roohi, & Khan, 2018). In a study, Li, Liu, Dai, Li, and Ding
(2018) found that MOS alone and in combination with inulin could
induce immune-related genes like TLR (1, 2 and 3), STAT, anti-lipo­
polysaccharide factor (ALF), crustin and prophenoloxidase (proPo) in
shrimp. The combined diet helped shrimp to fight against Vibrio algi­
nolyticus and whispovirus infection and lowered fish mortality by in­
creasing expression of prophenoloxidase (proPo) followed by activation
of the innate immune system through stimulation of cytotoxin and
melanization.
7. MOS in animal husbandry
The poultry industry is one of the fastest growing sectors in the
world. In India, production of eggs and broilers is increasing 8–10%
annually (http://www.fao.org/3/x6170e2k.htm). Enteric diseases in
fowls are the main reason for the increased mortality and loss of pro­
ductivity in the poultry industry. Due to increasing multidrug resistance
in humans, several countries have banned the use of antibiotics in the
8
Food Chemistry xxx (xxxx) xxxx
poultry industry. Recently, prebiotic treatment has emerged as one of
the main alternatives to circumvent this issue (Patterson & Burkholder,
2003). Among different prebiotics, MOS are widely used in poultry
farming and several recent studies highlight its importance. When both
forms of MOS and cMOS, were applied on greater amberjack (Seriola
dumerili), it reduced the feed conversion rate (FCR) and helped to up-
regulate MUC-2 in skin for mucus production. cMOS, a second gen­
eration MOS obtained from engineered S. cerevisiae with high-mannan
cell wall (Alltech®), helped to prevent the parasitic attachment of pa­
thogenic microorganisms due to increased IgT expression in skin. Be­
sides this, dietary intake of MOS increased piscidin while cMOS sup­
plementation enhanced hepcidin and defensin expression (Fernandez
et al., 2018). After the three types of dietary supplementations (basal
diet + organic acid, basal diet + MOS containing symbiotic and basal
diet + organic acid + MOS containing symbiotic), the MOS-containing
diet showed different metabolic changes in FCR and the concentration
of saturated long-chain fatty acid (palmitic acid) in breast muscle and
polyunsaturated fatty acids were decreased. On the other hand, total
serum protein, globulin, level of GSH, oleic acid in breast and amino
acids (leucine, methionine and histidine) were significantly increased in
Ross 308 chicks. It also improved different feed digestion pathways and
reduced the population of pathogens in the intestinal tract (Salah,
Ahmed-Farid, & El-Tarabany, 2019). Garcia Diaz et al. (2018) demon­
strated that MOS supplementation in cattle diets (Holstein steers) in­
creased the concentration of isobutyrate and valerate. The MOS diet led
to the stabilization of ruminal pH leading to elevation of populations of
lactate-utilizing bacteria such as Megasphaera elsdenii and Selenomonas
ruminantium by reducing serum amyloid A and ruminal ammonia con­
centrations.
Due to global warming, rise in temperatures is adversely affecting
broiler production. Under high temperature conditions, MOS-con­
taining synbiotic improved body weight gain and FCR, thus overcoming
the negative impact. Effect of prebiotic MOS supplementation led to the
reduction of abdominal fat deposition (Abdel-Wareth et al., 2018).
Cyclic heat conditions in chickens introduces production of superoxide
ions, increases serum corticosterone, induces accumulation of MDA and
disrupts the SOD and GSH-Px. MOS treatments helped in recovering
appetite and improved feed consumption by stimulating gastro­
intestinal maturation and enhancing nutrient absorption under cyclic
heat stress conditions (Cheng et al., 2018). MOS consumption led to the
increased concentration of HDL, globulin, total protein and tri-io­
dothyronine in serum while decreasing the triglyceride concentration in
female Japanese quail (Coturnix japonica). MOS have been shown to
confer beneficial health effects in monogastric animals with single
chambered stomach such as humans, rats, dogs and pigs. Similarly,
MOS supplementation has been shown to improve digestibility of ADF,
NDF and nitrogen retention by promoting cellulolytic bacterial popu­
lation in polygastric ruminant animals such as cow, goat and sheep. The
cellulolytic bacteria dwelling in the ruminant stomach help with fiber
breakdown and promote ruminal microorganisms to generate digestible
microbial proteins. In sheep, MOS supplementation (1.6% and 2.0%)
enhanced fiber digestibility, total antioxidant capacity and moderated
nitrogen retention (Zheng, Li, Hao, & Liu, 2018). Immunoglobulin G
(IgG) is one of the major glycosylated immunological proteins found in
colostrum (Uruakpa, Ismond, & Akobundu, 2002). Dietary MOS sup­
plementation (1.33%) on Holstein cross Friesian cows increased the
quantity of colostrum. However, IgG concentration and total mass of
IgG was not influenced by the supplement (Westland, Martin, White, &
Martin, 2017). In humans, salmonellosis is one of the major transmitted
diseases arising from the consumption of Salmonella-infected animal
products. In a study, results showed that addition of ≥2 kg/ton of β-
GMOS in pig diets during the entire growth period significantly reduced
Salmonella shedding, prevalence and sero-conversion (Andres-Barranco,
Vico, Grillo, & Mainar-Jaime, 2014).

Table 3
Animal health promotion using prebiotic mannooligosaccharides.
Animal
Holstein steers
Juveniles amberjack (Seriola dumerili
Risso 1810)
Chicks (Ross 308, 160 days old)
Chicks (Ross 308, 1 days old)
Chicks
Arbor acres
plus, 144 days old)
Pigs (Topigs®)
Japanese quail breeders (Coturnix
coturnix japonica)
Chicks (Ross 308, 420 days old)
9
Pacific white shrimp (Litopenaeus
vannamei)
Murrah buffalo calves
Sheep
Chicks (Arbor acres plus, 1 days old)
Chicks
Arbor acres
plus, 1 days old) Salmonella
enteritidis
Rainbow trout (Oncorhynchus mykiss)
Holstein cross Friesian cows
Chicks (Ross 308, 144 days old)
challenged with S. typhimurium
Chicks (Arbor acres plus, 1 days old)
challenged with E. coli O78
U.K. Jana, et al.
MOS type Sample size and MOS dose Outcome Reference
SAF-mannan Yeast (1.5 g/kg DM live yeast S. cerevisiae NCYC 996) and MOS Increase in isobutyric acid supplement with yeast and MOS; (Garcia Diaz et al., 2018)
(1.5 g/kg DM MOS, β-glucans and mannan) up to 21 days. Decrease in isovaleric acid
Bio-Mos® 5 g/kg MOS, 2 g/kg cMOS or a combination of both prebiotics cMOS induced a significant increase of serum bactericidal (Fernandez-Montero et al.,
Actigen® (cMOS) for 90 days. activity. 2019)
ICEC-TROL® synbiotic Basal diet + ICEC-TROL® synbiotic (1 g/kg) Synbiotic supplement improved PUFA: SFA ratio by altering the (Salah et al., 2019)
fatty acid in chick muscles.
Bio-Mos® n = 150, MOS 0, 0.5 or 1 g/kg of the starter diets and 0, 0.25 or Cholesterol and LDL-cholesterol decreased in serum (Abdel-Wareth et al.,
0.5 g/kg of the grower diets for 6 weeks. 2018)
SAF-Mannan n = 8, 1 g/kg MOS for 4 to 42 days. Promoted growth and reduced serum corticosterone (Cheng et al., 2018)
concentration
Bio-Mos® n = 20, 0.2% of MOS for 35 days Increase in CD4+CD8+ T lymphocytes (Valpotic et al., 2018)
– n = 60, corn-based basal diet with addition of 0.25%, 0.5% and Increase in total proteins, globulin, HDL and tri iodothyronine (Iqbal et al., 2018)
1% MOS for 15 week. (T3).
Active MOS® n = 60, diet with S. typhimurium and 2 g/kg mannan- Restoration of protease and amylase activity and jejunum villus (Jazi et al., 2018)
oligosaccharides height (VH) and VH to crypt depth (CD) ratio upon control
challenged with S. typhimurium
Bio-Mos® n = 150, MOS (2.5 mg/g, 5 mg/g 10 mg/g diet) + Inulin for Enhanced innate immune response and pathogen resistance of (Li et al., 2018)
28 days shrimp
– n = 20, MOS at 4 g/calf/day and Lactobacillus acidophilus in the Improved performance and faecal characteristics. Positively (Sharma, Kumar, & Tyagi,
form of fermented milk at 200 mL/calf/day + MOS altered faecal ammonia, lactate and pH. 2018)
Bio-Mos® n = 12, supplemental MOS at 0%, 1.2%, 1.6% and 2.0% kg−1 Increased neutral detergent fiber and acid detergent fiber. (Zheng et al., 2018)
of basal diet for 17 days
Bio-Mos® Bio-MOS at 0.5 g/kg diet Increase in the diameter of small and large follicles and splenic (Attia et al., 2017)
lymphoblast
Agri MOS MOS supplement with 1 g Increase in Enterococcus Ruminococcus and Coprococcus genera, (Pourabedin, Chen, Yang,
MOS/kg LITAF and interferon-γ in caecal tonsils & Zhao, 2016)
– – Increase in plasma glucose and triglyceride levels, reduced (Goncalves & Gallardo-
plasma enzyme activities Escarate, 2017)
– Provided 2 g/cow per day of MOS for 4 weeks Enhanced colostrum level (Westland et al., 2017)
Galacto-glucomannan n = 24, GGMs (0.1, 0.2 and 0.3%) and MOS at 0.2% Active Increased villus height and surface area; better growth (Rajani et al., 2016)
oligosaccharides from Pinus brutia MOS® for 24 days performance.
ActiveMOS®
SAF-mannan n = 540, 0.5 g/kg MOS for Reduced serum diamine oxidase and ileal myeloperoxidase (Wang et al., 2016)
Food Chemistry xxx (xxxx) xxxx
U.K. Jana, et al.
8. Human experimental data on MOS
The human gastrointestinal tract is full of variety of microorganisms
where they not only live in commensal relationships but also enter into
a synbiotic co-evolution with their host. In the case of a healthy adult,
gut microflora is dispersed over two major phyla, the Firmicutes
(Clostridium, Lactobacillus, Faecalibacterium and Enterococcus) and the
Bacteroidetes (Prevotella and Bacteroides) while minor phyla include
Proteobacteria, Actinobacteria (Bifidobacterium), Euryarchaeota and
Verrucomicrobia (Senghor, Sokhna, Ruimy, & Lagier, 2018). This bac­
terial population is significantly modulated by dietary prebiotics. Few
studies are available on the effect of MOS in humans and there is a
strong need of more conclusive research. Cardarelli et al. (2016) have
conducted a study with three healthy human females (H1, H2 and H3,
age group 30–40 years) and three pigs (P1, P2 and P3, age 1 year)
where the diet was supplemented with prebiotic MOS derived from KG
to evaluate the influence of Lactobacillus amylovorus DSM 16698 on
abundance of gut microbiota present in fecal and prebiotic carbohy­
drate fermentation patterns. Some experiments were conducted with
feces which were collected from both the hosts to measure L. amylo­
vorus count, carbon and ammonia assimilation, lactate, SCFA produc­
tion and change in pH. Results led to the conclusion that MOS admin­
istration enriched the population of Lactobacillus and other probiotic
organisms in both human and porcine gut. Pig microbiota was more
stable than human and KG oligosaccharides were more resistant to
fermentation than fructooligosaccharides and galactooligosaccharides.
After 24 h of fermentation, H3 completely degraded KG oligosacchar­
ides whereas H1, P2 and P3 did not show any degradation of KG oli­
gosaccharides (DP 3–6) indicating that H3 was rich in methanogenic
metabolism and sugar to SCFA conversion. In another clinical study, 54
men and women were administered either coffee containing MOS or a
placebo beverage for up to 11 weeks. Results showed that total body
volume and body weight was found to be reduced in the MOS supple­
mented group. Additionally, diastolic blood pressure was decreased in
those who consumed the MOS-containing beverage (Salinardi, Rubin,
Black, & St-Onge, 2010). Similarly, MOS derived from spent coffee
grounds was consumed (3 g per day by 8 healthy volunteers, 2 male and
6 female) over a period of 2 weeks. After that, a 2 week no-dose interval
period was applied followed by 1.0 g/day MOS for 2 weeks. MOS was
administered with either water or green tea. The results obtained from
this study suggested that consumption of MOS by each individual led to
increased populations of Bifidobacteria in the intestine and improved
defecation (Asano, Umemura, Fujii, Hoshino, & Iino, 2004). Walton
et al. (2010) selected 31 individuals (18 females and 13 males) ranging
from 18 to 39 year old and assigned to consume either placebo coffee
preparations, coffee supplemented with 3 g MOS or coffee supple­
mented with 5 g MOS per day for 3 weeks. Analysis of fecal samples
from this study suggested that the consumption of 3 g MOS daily can
increase probiotic growth, particularly, Bifidobacteria, and increase
SCFA production.
9. Conclusion and future perspectives
Development of new prebiotics has the potential to make a large
impact in nutraceutical and functional food research and applications.
MOS could be easily derived from non-food low-value mannan-rich
agricultural wastes after enzymatic and chemical treatments. Based on
value-addition, rapid generation and efficient purification will lead to
cost-effective availability of MOS. MOS, being a functional nu­
traceutical, confer a variety of advantages in different biological pro­
cesses and impart valuable benefits such as anti-cancer, anti-in­
flammatory and immuno-modulating properties. In the light of earlier
studies on MOS, it can be concluded that these have numerous appli­
cations and advantages in pharmaceutical and nutraceutical sectors
which must be explored further for human and animal health benefits.
10
Food Chemistry xxx (xxxx) xxxx
CRediT authorship contribution statement
Uttam Kumar Jana: Conceptualization, Visualization, Writing -
original draft, Writing - review & editing. Rahul Kumar Suryawanshi:
Writing - original draft, Writing - review & editing. Bhanu Pratap
Prajapati: Writing - review & editing. Naveen Kango: Supervision,
Resources, Writing - review & editing.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influ­
ence the work reported in this paper.
Acknowledgements
Author UKJ is grateful to ICMR, New Delhi for providing financial
assistance as Senior Research Fellow (SRF). The infrastructural support
of sophisticated instrumentation centre and DST-PURSE (II) at Dr.
Harisingh Gour Vishwavidyalaya, Sagar is duly acknowledged. Figure 2
was generated with the help of Biorender (biorender.com).
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://
doi.org/10.1016/j.foodchem.2020.128328.
References
Aachary, A. A., & Prapulla, S. G. (2010). Xylooligosaccharides (XOS) as an emerging
prebiotic: Microbial synthesis, utilization, structural characterization, bioactive
properties, and applications. Comprehensive Reviews in Food Science and Food Safety,
10, 2–16.
Abdel-Wareth, A. A. A., Hassan, H. A., Abdelrahman, W., Ismail, Z. S. H., Ali, R. A. M.,
Ahmed, E. A., & Lohakare, J. (2018). Growth performance, carcass criteria, and
serum biochemical parameters of broiler chickens supplemented with either synbiotic
or prebiotic under hot climatic conditions. British Poultry Science, 59(6), 663–668.
Albrecht, S., van Muiswinkel, G. C. J., Xu, J., Schols, H. A., Voragen, A. G. J., & Gruppen,
H. (2011). Enzymatic production and characterization of konjac glucomannan oli­
gosaccharides. Journal of Agriculture and Food Chemistry, 59(23), 12658–12666.
Andres-Barranco, S., Vico, J. P., Grillo, M. J., & Mainar-Jaime, R. C. (2014). Reduction of
subclinical Salmonella infection in fattening pigs after dietary supplementation with a
β-galactomannan oligosaccharide. Journal of Applied Microbiology, 118, 284–294.
Arnling Baath, J., Martínez-Abad, A., Berglund, J., Larsbrink, J., Vilaplana, F., & Olsson,
L. (2018). Mannanase hydrolysis of spruce galactoglucomannan focusing on the in­
fluence of acetylation on enzymatic mannan degradation. Biotechnology for Biofuels,
11, 114.
Asano, I., Nakamura, Y., Hoshino, H., Aoki, K., Fujii, S., Imura, N., & Iino, H. (2001). Use
of mannooligosaccharides from coffee mannan by intestinal bacteria. Journal of the
Agricultural Chemical Society of Japan, 75(10), 1077–1083.
Asano, I., Umemura, M., Fujii, S., Hoshino, H., & Iino, H. (2004). Effects of mannooli­
gosaccharides from coffee mannan on fecal microflora and defecation in healthy
volunteers. Journal of Food Science and Technology, 10(1), 93–97.
Astray, G., Gullon, B., Labidi, J., & Gullon, P. (2016). Comparison between developed
models using response surface methodology (RSM) and artificial neural networks
(ANNs) with the purpose to optimize oligosaccharide mixtures production from sugar
beet pulp. Industrial Crops and Products, 92, 290–299.
Attia, Y. A., Al-Khalaifah, H., Ibrahim, M. S., Al-Hamid, A. E. A., Al-Harthi, M. A., & El-
Naggar, A. (2017). Blood hematological and biochemical constituents, antioxidant
enzymes, immunity and lymphoid organs of broiler chicks supplemented with pro­
polis, bee pollen and mannan oligosaccharides continuously or intermittently. Poultry
Science, 96(12), 4182–4192.
Bortoluzzi, C., Barbosa, J., Pereira, R., Fagundes, N., Rafael, J., & Menten, J. (2018).
Autolyzed yeast (Saccharomyces cerevisiae) supplementation improves performance
while modulating the intestinal immune-system and microbiology of broiler chickens.
Frontiers in Sustainable Food Systems, 2, 85.
Cardarelli, H. R., Martinez, R. C. R., Albrecht, S., Schols, H., Franco, B. D. G. M., Saad, S.
M. I., & Smidt, H. (2016). In vitro fermentation of prebiotic carbohydrates by in­
testinal microbiota in the presence of Lactobacillus amylovorus DSM 16998. Beneficial
Microbes, 7(1), 119–133.
Cerqueira, M. A., Souza, B. W. S., Simoes, J., Teixeira, J. A., Domingues, M. R. M.,
Coimbra, M. A., & Vicente, A. A. (2011). Structural and thermal characterization of
galactomannans from non-conventional sources. Carbohydrate Polymers, 83(1),
179–185.
Chaikaew, S., Kanpiengjai, A., Intatep, J., Unban, K., Wongputtisin, P., Takata, G., &
Khanongnuch, C. (2016). X-ray-induced mutation of Bacillus sp. MR10 for manno-
U.K. Jana, et al.
oligosaccharides production from copra meal. Preparative Biochemistry and
Biotechnology, 47, 424–433.
Chatterjee, S., Khunti, K., & Davies, M. J. (2017). Type 2 diabetes. The Lancet,
389(10085), 2239–2251.
Chauhan, P. S., Sharma, P., Puri, N., & Gupta, N. (2014). Purification and characterization
of an alkali-thermostable β-mannanase from Bacillus nealsonii PN-11 and its appli­
cation in mannooligosaccharides preparation having prebiotic potential. European
Food Research and Technology, 238(6), 927–936.
Chen, W. L., Chen, H. L., Guo, G. W., Huang, Y. C., Chen, C. Y., Tsai, Y. U., ... Yang, C. H.
(2018). Locust bean gum galactomannan hydrolyzed by thermostable β-d-mannanase
may reduce the secretion of pro-inflammatory factors and the release of granule
constituents. International Journal of Biological Macromolecules, 114, 181–186.
Chen, W. L., Liang, J. B., Faseleh Jahromi, M., Abdullah, N., Ho, Y. W., & Tufarelli, V.
(2015). Enzyme treatment enhances release of prebiotic oligosaccharides from palm
kernel expeller. BioResources, 10, 196–209.
Cheng, Y., Du, M., Xu, Q., Chen, Y., Wen, C., & Zhou, Y. (2018). Dietary mannan oligo­
saccharide improves growth performance, muscle oxidative status, and meat quality
in broilers under cyclic heat stress. Journal of Thermal Biology, 75, 106–111.
Couturier, M., Feliu, J., Bozonnet, S., Roussel, A., & Berrin, J. (2013). Molecular en­
gineering of fungal GH5 and GH26 β-(1,4)-mannanases toward improvement of en­
zyme activity. PLoS ONE, 8(11), Article e79800.
De Vadder, F., Kovatcheva-Datchary, P., Goncalves, D., Vinera, J., Zitoun, C., Duchampt,
A., Bäckhed, F., & Mithieux, G. (2014). Microbiota-generated metabolites promote
metabolic benefits via gut-brain neural circuits. Cell, 156(1-2), 84–96.
Endo, A., Nakamura, S., Konishi, K., Nakagawa, J., & Tochio, T. (2016). Variations in
prebiotic oligosaccharide fermentation by intestinal lactic acid bacteria. International
Journal of Food Sciences and Nutrition, 67(2), 125–132.
Faseleh Jahromi, M., Liang, J. B., Abdullah, N., Goh, Y. M., Ebrahimi, R., & Shokryazdan,
P. (2016). Extraction and characterization of oligosaccharides from palm kernel cake
as prebiotic. BioResources, 11, 674–695.
Ferenczi, S., Szegi, K., Winkler, Z., Barna, T., & Kovacs, K. J. (2016). Oligomannan pre­
biotic attenuates immunological, clinical and behavioral symptoms in mouse model
of inflammatory bowel disease. Scientific Reports, 6(1), Article 34132.
Fernandez, J., Moreno, F., Olano, A., Clemente, A., Villar, C., & Lombo, F. (2018). A
galacto-oligosaccharides preparation derived from lactulose protects against color­
ectal cancer development in an animal model. Frontiers in Microbiology, 9, 2004.
Fernandez-Montero, A., Torrecillas, S., Izquierdo, M., Caballero, M. J., Milne, D. J.,
Secombes, C. J., ... Montero, D. (2019). Increased parasite resistance of greater am­
berjack (Seriola dumerili Risso 1810) juveniles fed a cMOS supplemented diet is as­
sociated with upregulation of a discrete set of immune genes in mucosal tissues. Fish
& Shellfish Immunology, 86, 35–45.
Fowler, J., Kakani, R., Haq, A., Byrd, J. A., & Bailey, C. A. (2015). Growth promoting
effects of prebiotic yeast cell wall products in starter broilers under an immune stress
and Clostridium perfringens challenge. Journal of Applied Poultry Research, 24(1),
66–72.
Fructooligosaccharides Market, FOS Industry Report, 2024. https://www.
grandviewresearch.com/industry-analysis/fructooligosaccharides-market. Last ac­
cessed date 24.01.2020.
Garcia Diaz, T., Ferriani Branco, A., Jacovaci, F. A., Cabreira Jobim, C., Pratti Daniel, J.
L., Iank Bueno, A. V., & Goncalves Ribeiro, M. (2018). Use of live yeast and mannan-
oligosaccharides in grain-based diets for cattle: Ruminal parameters, nutrient di­
gestibility, and inflammatory response. PLOS One, 13(11).
Ghosh, A., Verma, A. K., Tingirikari, J. R., Shukla, R., & Goyal, A. (2015). Recovery and
purification of oligosaccharides from copra meal by recombinant endo-β-mannanase
and deciphering molecular mechanism involved and its role as potent therapeutic
agent. Molecular Biotechnology, 57(2), 111–127.
Gibson, G. R., Hutkins, R., Sanders, M. E., Prescott, S. L., Reimer, R. A., Salminen, S. J.,
Scott, K., Stanton, C., Swanson, K. S., Cani, P. D., Verbeke, K., & Reid, G. (2017).
Expert consensus document: the international scientific association for probiotics and
prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics.
Nature Reviews Gastroenterology & Hepatology, 14(8), 491–502.
Glycoside Hydrolase family classification. http://www.cazy.org/Glycoside-Hydrolases.
html. Last accessed date 24.01.2020.
Gomez, B., Miguez, B., Yanez, R., & Alonso, J. L. (2017). Manufacture and properties of
glucomannans and glucomannooligosaccharides derived from konjac and other
sources. Journal of Agriculture and Food Chemistry, 65(10), 2019–2031.
Goncalves, A. T., & Gallardo-Escarate, C. (2017). Microbiome dynamic modulation
through functional diets based on pre- and probiotics (mannan-oligosaccharides and
Saccharomyces cerevisiae) in juvenile rainbow trout (Oncorhynchus mykiss). Journal of
Applied Microbiology, 122(5), 1333–1347.
Gonzalez, P. S., O’Prey, J., Cardaci, S., Barthet, V. J. A., Sakamaki, J., Beaumatin, F., ...
Malviya, G. (2018). Mannose impairs tumour growth and enhances chemotherapy.
Nature, 563(7733), 719–723.
Guo, S., Mao, W., Yan, M., Zhao, C., Li, N.a., Shan, J., Lin, C., Liu, X., Guo, T., Guo, T., &
Wang, S. (2014). Galactomannan with novel structure produced by the coral en­
dophytic fungus Aspergillus ochraceus. Carbohydrate Polymers, 105, 325–333.
Haki, G. D., & Rakshit, S. K. (2003). Developments in industrially important thermostable
enzymes: A review. Bioresource Technology, 89(1), 17–34.
Hogg, D., Pell, G., Dupree, P., Goubet, F., Martin-orue, S. M., Armand, S., & Gilbert, H. J.
(2003). The modular architecture of Cellvibrio japonicus mannanases in glycoside
hydrolase families 5 and 26 points to differences in their role in mannan degradation.
Biochemical Journal, 371, 1027–1043.
Hoshino-Takao, I., Fujii, S., Ishii, A., Han, L.-K., Okuda, H., & Kumao, T. (2008). Effects of
mannooligosaccharides from coffee mannan on blood pressure in dahl salt-sensitive
rats. Journal of Nutritional Science and Vitaminology, 54(2), 181–184.
Hoving, L. R., Katiraei, S., Heijink, M., Pronk, A., van der Wee-Pals, L., Streefland, T., ...
11
Food Chemistry xxx (xxxx) xxxx
van Harmelen, V. (2018a). Dietary mannan oligosaccharides modulate gut micro­
biota, increase fecal bile acid excretion, and decrease plasma cholesterol and ather­
osclerosis development. Molecular Nutrition & Food Research, 62(10), 1700942.
Hoving, L. R., van der Zande, H. J. P., Pronk, A., Guigas, B., Willems van Dijk, K., van
Harmelen, V., & Willems van Dijk, V. (2018b). van Harmelen Dietary yeast-derived
mannan oligosaccharides have immune-modulatory properties but do not improve
high fat diet-induced obesity and glucose intolerance. PLoS One, 13, 5.
Iqbal, M. A., Roohi, N., & Khan, O. (2018). Dietary supplemented effects of mannan-
oligosaccharides on biochemical parameters of 4 close-bred flocks of Japanese quail
breeders. Poultry Science, 97(10), 3718–3727.
Jana, U. K., & Kango, N. (2020). Characteristics and bioactive properties of mannooli­
gosaccharides derived from agro-waste mannans. International Journal of Biological
Macromolecules, 149, 931–940.
Jana, U. K., Suryawanshi, R. K., Prajapati, B. P., Soni, H., & Kango, N. (2018). Production
optimization and characterization of mannooligosaccharide generating β-mannanase
from Aspergillus oryzae. Bioresource Technology, 268, 308–314.
Jazi, V., Foroozandeh, A. D., Toghyani, M., Dastar, B., Rezaie Koochaksaraie, R., &
Toghyani, M. (2018). Effects of Pediococcus acidilactici, mannan-oligosaccharide,
butyric acid and their combination on growth performance and intestinal health in
young broiler chickens challenged with Salmonella typhimurium. Poultry Science,
97(6), 2034–2043.
Jian, W., Sun, Y., Huang, H., Yang, Y., Peng, S., Xiong, B.o., Pan, T., Xu, Z., He, M., &
Pang, J. (2013). Study on preparation and separation of Konjac oligosaccharides.
Carbohydrate Polymers, 92(2), 1218–1224.
Kalidas, N. R., Saminathan, M., Ismail, I. S., Abas, F., Maity, P., Islam, S. S., Manshoor, N.,
& Shaari, K. (2017). Structural characterization and evaluation of prebiotic activity of
oil palm kernel cake mannanoligosaccharides. Food Chemistry, 234, 348–355.
Kango, N., Jana, U. K., & Choukade, R. (2019). Fungal Enzymes: Sources and
Biotechnological Applications. 515–538. https://doi.org/10.1007/978-981-13-9349-
5_21.
Kawaguchi, K., Senoura, T., Ito, S., Taira, T., Ito, H., Wasaki, J., & Ito, S. (2014). The
mannobiose-forming exo-mannanase involved in a new mannan catabolic pathway in
Bacteroides fragilis. Archives of Microbiology, 196(1), 17–23.
Li, Y., Liu, H., Dai, X., Li, J., & Ding, F. (2018). Effects of dietary inulin and mannan
oligosaccharide on immune related genes expression and disease resistance of Pacific
white shrimp, Litopenaeus vannamei. Fish & Shellfish Immunology, 76, 78–92.
Li, Y. X., Yi, P., Liu, J., Yan, Q. J., & Jiang, Z. Q. (2018). High-level expression of an
engineered β-mannanase (mRmMan5A) in Pichia pastoris for manno-oligosaccharide
production using steam explosion pretreated palm kernel cake. Bioresource
Technology, 256, 30–37.
Liao, H., Li, S., Zheng, H., Wei, Z., Liu, D., Raza, W., ... Xu, Y. (2014). A new acidophilic
thermostable endo-1,4-β-mannanase from Penicillium oxalicum GZ-2: Cloning, char­
acterization and functional expression in Pichia pastoris. BMC Biotechnology, 14(1),
https://doi.org/10.1186/s12896-014-0090-z.
Liu, J., Leppanen, A. S., Kisonen, V., Willfor, S., Xu, C., & Vilaplana, F. (2018). Insights on
the distribution of substitutions in spruce galactoglucomannan and its derivatives
using integrated chemo-enzymatic deconstruction, chromatography and mass spec­
trometry. International Journal of Biological Macromolecules, 112, 616–625.
Liu, Y., Chen, J., Tan, Q., Deng, X., Tsai, P. J., Chen, P. H., ... Su, Z. (2020b). Nondigestible
oligosaccharides with anti-obesity effects. Journal of Agriculture and Food Chemistry,
68(1), 4–16.
Liu, Z., Ning, C., Yuan, M., Yang, S., Wei, X., Xiao, M., ... Mou, H. (2020a). High-level
expression of a thermophilic and acidophilic β-mannanase from Aspergillus kawachii
IFO 4308 with significant potential in mannooligosaccharide preparation. Bioresource
Technology, 295, 122257.
Luo, Z., Miao, J., Li, G., Du, Y., & Yu, X. (2017). A recombinant highly hhermostable β-
mannanase (ReTMan26) from thermophilic Bacillus subtilis (TBS2) expressed in Pichia
pastoris and its pH and temperature stability. Applied Biochemistry and Biotechnology,
182(4), 1259–1275.
Ma, L., Ma, Q., Cai, R., Zong, Z., Du, L., Guo, G., ... Xiaoa, D. (2017). Effect of β-man­
nanase domain from Trichoderma reesei on its biochemical characters and synergistic
hydrolysis of sugarcane bagasse. Journal of the Science of Food and Agriculture, 98,
2540–2547.
Ma, Y., Uemura, K., Oka, S., Kozutsumi, Y., Kawasaki, N., & Kawasaki, T. (1999).
Antitumor activity of mannan-binding protein in vivo as revealed by a virus ex­
pression system: Mannan-binding proteindependent cell-mediated cytotoxicity.
Proceedings of the National Academy of Sciences, 96(2), 371–375.
Macfarlane, S., Macfarlane, G. T., & Cummings, J. H. (2006). Review article: Prebiotics in
the gastrointestinal tract. Alimentary Pharmacology & Therapeutics, 24(5), 701–714.
Malgas, S., van Dyk, S. J., & Pletschke, B. I. (2015). β-Mannanase (Man26A) and α-ga­
lactosidase (Aga27A) synergism – A key factor for the hydrolysis of galactomannan
substrates. Enzyme and Microbial Technology, 70, 1–8.
Mao, Y. H., Song, A. X., Yao, Z. P., & Wu, J. Y. (2018). Protective effects of natural and
partially degraded konjac glucomannan on Bifidobacteria against antibiotic damage.
Carbohydrate Polymers, 181, 368–375.
Martin, R., Chamignon, C., Mhedbi-Hajri, N., Chain, F., Derrien, M., Escribano-Vazquez,
U., ... Langella, P. (2019). The potential probiotic Lactobacillus rhamnosus CNCM I-
3690 strain protects the intestinal barrier by stimulating both mucus production and
cytoprotective response. Scientific Reports, 9(1), https://doi.org/10.1038/s41598-
019-41738-5.
Mary, P. R., Prashanth, K. V. H., Vasu, P., & Kapoor, M. (2019). Structural diversity and
prebiotic potential of short chain β-manno-oligosaccharides generated from guar gum
by endo-β-mannanase (ManB-1601). Carbohydrate Research, 486, 107822.
Marzaioli, A. M., Bedini, E., Lanzetta, R., Parrilli, M., & De Castro, C. (2014). Conversion
of yeast mannan polysaccharide in mannose oligosaccharides with a thiopropargyl
linker at the pseudo-reducing end. Carbohydrate Research, 383, 43–49.
U.K. Jana, et al.
Mikkelson, A., Maaheimo, H., & Hakala, T. K. (2013). Hydrolysis of konjac glucomannan
by Trichoderma reesei mannanase and endoglucanases Cel7B and Cel5A for the pro­
duction of glucomannooligosaccharides. Carbohydrate Research, 372, 60–68.
Miyazawa, T., & Funazukuri, T. (2006). Noncatalytic hydrolysis of guar gum under hy­
drothermal conditions. Carbohydrate Research, 341(7), 870–877.
Nakajima, A., & Ballo, C. E. (1974). Characterization of the carbohydrate fragments ob­
tained from Saccharomyces cerevisiae mannan by alkaline degradation. Journal of
Biological Chemistry, 249, 7679–7684.
Nattorp, A., Graf, M., Spuhler, C., & Renken, A. (1999). Model for random hydrolysis and
end degradation of linear polysaccharides: Application to the thermal treatment of
mannan in solution. Industrial & Engineering Chemistry Research, 38, 2919–2926.
Nopvichai, C., Charoenwongpaiboon, T., Luengluepunya, N., Ito, K., Muanprasat, C., &
Pichyangkura, R. (2019). Production and purification of mannan oligosaccharide
with epithelial tight junction enhancing activity. PeerJ, 7.
Nowacka-Jechalke, N., Nowak, R., Juda, M., Malm, A., Lemieszek, M., Rzeski, W., &
Kaczynski, Z. (2018). New biological activity of the polysaccharide fraction from
Cantharellus cibarius and its structural characterization. Food Chemistry, 268,
355–361.
Patterson, J. A., & Burkholder, K. M. (2003). Application of prebiotics and probiotics in
poultry production. Poultry Science, 82(4), 627–631.
Paulovicova, E., Paulovicova, L., Farkas, P., Karelin, A. A., Tsvetkov, Y. E., Krylov, V. B., &
Nifantiev, N. E. (2019). Importance of Candida antigenic factors: structure-driven
immunomodulation properties of synthetically prepared mannooligosaccharides in
RAW264.7 macrophages. Frontiers in Cellular and Infection Microbiology, 9, 378.
Pettey, L., Carter, S., Senne, B., & Shriver, J. (2002). Effects of beta-mannanase addition to
corn-soybean meal diets on growth performance, carcass traits, and nutrient digest­
ibility of weanling and growing-finishing pigs. Journal of Animal Science, 80(4),
1012–1019.
Pongsapipatana, N., Damrongteerapap, P., Chantorn, S., Sintuprapa, W., Keawsompong,
S., & Nitisinprasert, S. (2016). Molecular cloning of kman coding for mannanase from
Klebsiella oxytoca KUB-CW2-3 and its hybrid mannanase characters. Enzyme and
Microbial Technology, 89, 39–51.
Pourabedin, M., Chen, Q., Yang, M., & Zhao, X. (2016). Mannan- and xylooligosacchar­
ides modulate caecal microbiota and expression of inflammatory-related cytokines
and reduce caecal Salmonella enteritidis colonisation in young chickens. FEMS
Microbiology Ecology, 93, fiw226.
Pradeep, G. C., Cho, S. S., Choi, Y. H., Choi, Y. S., Jee, J. P., Seong, C. N., & Yoo, J. C.
(2016). An extremely alkaline mannanase from Streptomyces sp. CS428 hydrolyzes
galactomannan producing series of mannooligosaccharides. World Journal of
Microbiology and Biotechnology, 32, 84.
Prajapati, B. P., Jana, U. K., Suryawanshi, R. K., & Kango, N. (2020). Sugarcane bagasse
saccharification using Aspergillus tubingensis enzymatic cocktail for 2G bio-ethanol
production. Renewable Energy, 152, 653–663.
Prajapati, B. P., Suryawanshi, R. K., Agrawal, S., Ghosh, M., & Kango, N. (2018).
Characterization of cellulase from Aspergillus tubingensis NKBP-55 for generation of
fermentable sugars from agricultural residues. Bioresource Technology, 250, 733–740.
Prayoonthien, P., Rastall, R. A., Kolida, S., Nitisinprasert, S., & Keawsompong, S. (2019).
In vitro fermentation of copra meal hydrolysate by human fecal microbiota. 3 Biotech,
9(3), https://doi.org/10.1007/s13205-019-1633-8.
Praznik, W., Cavarkapa, A., Unger, F. M., Loeppert, R., Holzer, W., Viernstein, H., &
Mueller, M. (2017). Molecular dimensions and structural features of neutral poly­
saccharides from the seed mucilage of Hyptis suaveolens L. Food Chemistry, 221,
1997–2004.
Pronyk, C., Mazza, G., & Tamaki, Y. (2011). Production of carbohydrates, lignins, and
minor components from triticale straw by hydrothermal treatment. Journal of
Agriculture and Food Chemistry, 59(8), 3788–3796.
Rahmani, N., Kashiwagi, N., Lee, J., Niimi-Nakamura, S., Matsumoto, H., Kahar, P., ...
Kondo, A. (2017). Mannan endo-1, 4-β-mannosidase from Kitasatospora sp. isolated in
Indonesia and its potential for production of mannooligosaccharides from mannan
polymers. AMB Express, 7, 100.
Rajani, J., Dastar, B., Samadi, F., Karimi Torshizi, M. A., Abdulkhani, A., &
Esfandyarpour, S. (2016). Effect of extracted galactoglucomannan oligosaccharides
from pine wood (Pinus brutia) on Salmonella typhimurium colonisation, growth per­
formance and intestinal morphology in broiler chicks. British Poultry Science, 57(5),
682–692.
Ramirez-hernandez, A., Rupnow, J., & Hutkins, R. W. (2015). Adherence reduction of
Campylobacter jejuni and Campylobacter coli strains to HEp-2 cells by mannan oligo­
saccharides and a high-molecular-weight component of cranberry extract. Journal of
Food Protection, 78, 1496–1505.
Rivas, S., Gullon, B., Gullon, P., Alonso, J. L., & Parajo, J. C. (2012). Manufacture and
properties of bifidogenic saccharides derived from wood mannan. Journal of
Agriculture and Food Chemistry, 60(17), 4296–4305.
Rosengren, A., Reddy, S. K., Sjoberg, J. S., Aurelius, O., Logan, D. T., Kolenova, K., &
Stalbrand, H. (2014). An Aspergillus nidulans β-mannanase with high transglycosy­
lation capacity revealed through comparative studies within glycosidase family 5.
Applied Microbiology and Biotechnology, 98(24), 10091–10104.
Royce, L. A., Liu, P., Stebbins, M. J., Hanson, B. C., & Jarboe, L. R. (2013). The damaging
effects of short chain fatty acids on Escherichia coli membranes. Applied Microbiology
and Biotechnology, 97(18), 8317–8327.
Rungrassamee, W., Kingcha, Y., Srimarut, Y., Maibunkaew, S., Karoonuthaisiri, N., &
Visessanguan, W. (2014). Mannooligosaccharides from copra meal improves survival
of the Pacific white shrimp (Litopenaeus vannamei) after exposure to Vibrio harveyi.
Food Chemistry, 434, 403–410.
Safmannan® – Premium yeast fraction. https://phileo-lesaffre.com/en/products/yeast-
parietal-fraction-safmannan/. Last accessed date 24.01.2020.
Rungruangsaphakun, J., & Keawsompong, S. (2018). Optimization of hydrolysis
12
Food Chemistry xxx (xxxx) xxxx
conditions for the mannooligosaccharides copra meal hydrolysate production. 3
Biotech, 8(3), https://doi.org/10.1007/s13205-018-1178-2.
Salah, A. S., Ahmed-Farid, O. A., & El-Tarabany, M. S. (2019). Carcass yields, muscle
amino acid and fatty acid profiles, and antioxidant indices of broilers supplemented
with synbiotic and/or organic acids. Journal of Animal Physiololgy & Animal Nutrition,
103(1), 41–52.
Salinardi, T. C., Rubin, K. H., Black, R. M., & St-Onge, M. P. (2010). Coffee mannooli­
gosaccharides, consumed as part of a free-living, weight-maintaining diet, increase
the proportional reduction in body volume in overweight men. The Journal of
Nutrition, 140, 1943–1948.
Seesom, W., Thongket, P., Yamamoto, T., Takenaka, S., Sakamoto, T., & Sukhumsirichart,
W. (2017). Purification, characterization, and overexpression of an endo-1,4-β-
mannanase from thermotolerant Bacillus sp. SWU60. World Journal of Microbiology &
Biotechnology, 33(3), https://doi.org/10.1007/s11274-017-2224-7.
Senghor, B., Sokhna, C., Ruimy, R., & Lagier, J. C. (2018). Gut microbiota diversity ac­
cording to dietary habits and geographical provenance. Human Microbiome Journal, 7-
8, 1–9.
Senoura, T., Ito, S., Taguchi, H., Higa, M., Hamada, S., Matsui, H., ... Ito, S. (2011). New
microbial mannan catabolic pathway that involves a novel mannosylglucose phos­
phorylase. Biochemical and Biophysical Research Communications, 408(4), 701–706.
Sharma, A. N., Kumar, S., & Tyagi, A. K. (2018). Effects of mannan-oligosaccharides and
Lactobacillus acidophilus supplementation on growth performance, nutrient utilization
and faecal characteristics in Murrah buffalo calves. Journal of Animal Physiololgy &
Animal Nutrition, 102(3), 679–689.
Shimizu, M., Kaneko, Y., Ishihara, S., Mochizuki, M., Sakai, K., Yamada, M., ... Kato, M.
(2015). Novel β-1,4-mannanase belonging to a new glycoside hydrolase family in
Aspergillus nidulans. Journal of Biological Chemistry, 290(46), 27914–27927.
Singh, S., Ghosh, A., & Goyal, A. (2017). Manno-oligosaccharides as prebiotic-valued
products from agro-waste. Biosynthetic Technology and Environmental Challenges,
205–221.
Smith, R., Inomata, H., & Peters, C. (2013). Systems, Devices and Processes. 55–119.
https://doi.org/10.1016/B978-0-444-52215-3.00002-7.
Singh, V., Sethi, R., Tewari, A., Srivastava, V., & Sanghi, R. (2003). Hydrolysis of plant
seed gums by microwave irradiation. Carbohydrate Polymers, 54(4), 523–525.
Song, Y., Sun, W., Fan, Y., Xue, Y., Liu, D., Ma, C., ... Zhang, T. (2018). Galactomannan
degrading enzymes from the mannan utilization gene cluster of alkaliphilic Bacillus
sp. N16–5 and their synergy on galactomannan degradation. Journal of Agricultural
and Food Chemistry, 66, 11055–11063.
Soni, H., & Kango, N. (2013). Advances in Enzyme Biotechnology (pp. 41–56). New Delhi:
Springer India.
Soni, H., Rawat, H. K., Pletschke, B. I., & Kango, N. (2016). Purification and character­
ization of β-mannanase from Aspergillus terreus and its applicability in depolymer­
ization of mannans and saccharification of lignocellulosic biomass. 3 Biotech, 6(2).
Spring, P., Wenk, C., Dawson, K. A., & Newman, K. E. (2000). The effects of dietary
mannaoligosaccharides on cecal parameters and the concentrations of enteric bac­
teria in the ceca of salmonella-challenged broiler chicks. Poultry Science, 79(2),
205–211.
Srivastava, P. K., Panwar, D., Prashanth, K. V. H, & Kapoor, M. (2017). Structural char­
acterization and in vitro fermentation of β-mannooligosaccharides produced from
locust bean gum by GH-26 endo-β-1,4-mannanase (ManB-1601). Journal of
Agriculture and Food Chemistry, 65(13), 2827–2838.
St-Onge, M. P., Salinardi, T., Herron-Rubin, K., & Black, R. M. A. (2012). A weight-loss
diet including coffee-derived mannooligosaccharides enhances adipose tissue loss in
overweight men but not women. Obesity, 20(2), 343–348.
Suryawanshi, R. K., Jana, U. K., Prajapati, B. P., & Kango, N. (2019). Immobilization of
Aspergillus quadrilineatus RSNK-1 multi-enzymatic system for fruit juice treatment and
mannooligosaccharide generation. Food Chemistry, 289, 95–102.
Suryawanshi, R. K., & Kango, N. (2020). Production of mannooligosaccharides from
various mannans and evaluation of their prebiotic potential. Food Chemistry, 334,
Article 127428.
Thambiraj, S. R., Phillips, M., Koyyalamudi, S. R., & Reddy, N. (2018). Yellow lupin
(Lupinus luteus L.) polysaccharides: Antioxidant, immunomodulatory and prebiotic
activities and their structural characterisation. Food Chemistry, 267, 319–328.
Titapoka, S., Keawsompong, S., Haltrich, D., & Nitisinprasert, S. (2007). Selection and
characterization of mannanase-producing bacteria useful for the formation of pre­
biotic manno-oligosaccharides from copra meal. World Journal of Microbiology and
Biotechnology, 24, 1425–1433.
Uruakpa, F. O., Ismond, M. A. H., & Akobundu, E. N. T. (2002). Colostrum and its ben­
efits: A review. Nutrition Research, 22(6), 755–767.
Valpotic, H., ZuraZaja, I., Samardzija, M., Habrun, B., Ostovic, M., Duricic, D., ... Vince, S.
(2018). Dietary supplementation with mannan oligosaccharide and clinoptilolite
modulates innate and adaptive immune parameters of weaned pigs. Polish Journal of
Veterinary Sciences, 21, 83–93.
van Zyl, W. H., Rose, S. H., Trollope, K., & Gorgens, J. F. (2010). Fungal β-mannanases:
Mannan hydrolysis, heterologous production and biotechnological applications.
Process Biochemistry, 45(8), 1203–1213.
Walton, G. E., Rastall, R. A., Rastall, R. A., Martini, M. C., Williams, C. E., Jeffries, R. L., &
Gibson, G. R. (2010). A double-blind, placebo controlled human study investigating
the effects of coffee derived manno-oligosaccharides on the faecal microbiota of a
healthy adult population. International Journal of Probiotics and Prebiotics, 5 75e83.
Wang, H., Zhang, X., Wang, S., Li, H., Lu, Z., Shi, J., & Xu, Z. (2018). Mannan-oligo­
saccharide modulates the obesity and gut microbiota in high-fat diet-fed mice. Food &
Function, 9(7), 3916–3929.
Wang, W., Li, Z., Han, Q., Guo, Y., Zhang, B., & D’inca, R. (2016). Dietary live yeast and
mannan-oligosaccharide supplementation attenuate intestinal inflammation and
barrier dysfunction induced by Escherichia coli in broilers. British Journal of Nutrition,
U.K. Jana, et al.
116(11), 1878–1888.
Watanabe, K., Yaguchi, T., Yang, D., Kanno, T., Nagai, K., Yamamoto, S., ... Nishizaki, T.
(2006). Beneficial effect of intracellular free high-mannose oligosaccharides on
cryopreservation of mammalian cells and proteins. Cryobiology, 53(3), 330–335.
Westland, A., Martin, R., White, R., & Martin, J. H. (2017). Mannan oligosaccharide
prepartum supplementation: Effects on dairy cow colostrum quality and quantity.
Animal, 11(10), 1779–1782.
Xia, W., Lu, H., Xia, M., Cui, Y., Bai, Y., Qian, L., ... Yao, B. (2016). A novel glycoside
hydrolase family 113 endo-β-1,4-mannanase from Alicyclobacillus sp. strain A4 and
insight into the substrate recognition and catalytic mechanism of this family. Applied
and Environmental Microbiology, 82, 2718–2727.
Yang, C., Chung, D., Shin, I. S., Lee, H. Y., Kim, J. C., Lee, Y. J., & You, S. G. (2008).
Effects of molecular weight and hydrolysis conditions on anticancer activity of fu­
coidans from sporophyll of Undaria pinnatifida. International Journal of Biological
Macromolecules, 43(5), 433–437.
Yuliansyah, A. T., Kumagai, S., Hirajima, T., & Sasaki, K. (2019). Hydrothermal treatment
of oil palm biomass in batch and semi-flow reactors. Energy Procedia, 158, 675–680.
Zang, H., Xie, S., Wu, H., Wang, W., Shao, X., Wu, L., ... Gao, X. (2015). A novel
13
Food Chemistry xxx (xxxx) xxxx
thermostable GH5_7 β-mannanase from Bacillus pumilus GBSW19 and its application
in manno-oligosaccharides (MOS) production. Enzyme and Microbial Technology,
78, 1–9.
Zheng, C., Li, F., Hao, Z., & Liu, T. (2018). Effects of adding mannan oligosaccharides on
digestibility and metabolism of nutrients, ruminal fermentation parameters, im­
munity, and antioxidant capacity of sheep. Journal of Animal Science, 96, 284–292.
Zheng, J., Li, H., Zhang, X., Jiang, M., Luo, C., Lu, Z., ... Shi, J. (2018). Prebiotic mannan-
oligosaccharides augment the hypoglycemic effects of metformin in correlation with
modulating gut microbiota. Journal of Agriculture and Food Chemistry, 66(23),
5821–5831.
Zhou, C., Xue, Y., & Ma, Y. (2018). Characterization and high-efficiency secreted ex­
pression in Bacillus subtilis of a thermo-alkaline β-mannanase from an alkaliphilic
Bacillus clausii strain S10. Microbial Cell Factories, 17(1), https://doi.org/10.1186/
s12934-018-0973-0.
Zhou, M., Yang, L., Yang, S., Zhao, F., Xu, L., & Yong, Q. (2018). Isolation, character­
ization and in vitro anticancer activity of an aqueous galactomannan from the seed of
Sesbania cannabina. International Journal of Biological Macromolecules, 113,
1241–1247.