Journal of Functional Foods 104 (2023) 105520

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Journal of Functional Foods

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

Chitosan and chitosan‑based composites as beneficial compounds for

animal health: Impact on gastrointestinal functions and
biocarrier application
Victoria Anthony Uyanga a, Onome Ejeromedoghene b, Modinat Tolani Lambo c,
Michael Alowakennu d, Yakubu Adekunle Alli e, Abigail Adamma Ere-Richard f, Liu Min a,
Jingpeng Zhao a, Xiaojuan Wang a, Hongchao Jiao a, Okanlawon M. Onagbesan g, Hai Lin a, *
a
College of Animal Science and Technology, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Key Laboratory of
Efficient Utilization of Non-grain Feed Resources (Co-construction by Ministry and Province), Ministry of Agriculture and Rural Affairs, Shandong Agricultural
University, Tai’an 271018, China
b
School of Chemistry and Chemical Engineering, Southeast University, Jiangning District, Nanjing, Jiangsu Province 211189, China
c
College of Animal Science and Technology, Northeast Agricultural University, Harbin, China
d
Michigan State University, East Lansing, MI 48823, USA
e
French National Centre for Scientific Research, Laboratory of Coordination Chemistry (LCC) – UPR, 824-205 Route de Narbonne, BP44099-31077 Toulouse, France
f
Department of Animal Science, University of Port Harcourt, Nigeria
g
Department of Animal Physiology, Federal University of Agriculture, Abeokuta P.M.B. 2240, Ogun State, Nigeria

A R T I C L E I N F O A B S T R A C T

Keywords: Chitosan and chitosan-based composites are increasingly gaining attention as feed additives in animal produc­
Chitosan tion. However, few studies have summarized their multifunctional roles and applications in animals. This review
Biocarrier presents an extensive overview of chitosan and chitosan-based composites in animal nutrition, with emphasis on
Chitosan oligosaccharides
their roles in gastrointestinal function and substance delivery. It is surmised that the supplementation of chitosan
Feed additives
Animal nutrition
and its derivatives to animals improves the growth performance, productivity, nutrient digestibility, antioxidant
Gut health capacity, gut health, immunity, and health status of animals. Additionally, the encapsulation of chitosan-based
composites as bioactive agents for nutrient, drug, and vaccine delivery enhances the nutritional qualities of
animal feeds and boosts animal health. Therefore, a comprehensive understanding of the potentials of chitosan
and chitosan-based composites as feed additives, their actions on gastrointestinal health and bio-delivery, and
the challenges underlying their applications would promote their effective and efficient utilization for animal
production and foster research progress in this field.

1. Introduction (Founou et al., 2016). Notwithstanding, it is necessary to develop non-

In animal production, feed additives are routinely used to improve
animal health and productivity. Various ingredients are incorporated
during feed formulation with the end goal of producing nutritious diets
that would improve productivity, metabolism, health, and welfare
(Swiatkiewicz et al., 2015). Besides, the traditional additives used in
livestock management were primarily substances with antimicrobial
activity (Van et al., 2020). However, the broad use of antibiotics for
human and animal health has been widely discouraged due to their
residual effects on animal products and waste, the development of mi­
crobial pathogenic resistant strains, and environmental contamination
conventional diets containing natural and cost-effective ingredients in
order to meet protein demand and supply, and achieve sustainable an­
imal production (Uyanga et al., 2022; Wanapat et al., 2015). This has
heightened the search for antibiotic alternatives that can promote dis­
ease resistance, boost productivity, and maintain animal health (Reddy
et al., 2018). Several additives such as selenium (Dhaliwal et al., 2022;
Surai et al., 2018), oligosaccharides (prebiotics) (Anadón et al., 2019;
Kim et al., 2019), antibiotics (Bacanlı & Başaran, 2019; Chowdhury
et al., 2021), and microbes (probiotic) (Abd El-Hack,El-Saadony, Shafi,
Zabermawi et al., 2020; Abd El-Hack, El-Saadony, Shafi, Qattan et al.,
2020; Anadón et al., 2019; Liao & Nyachoti, 2017) have been utilized as

* Corresponding author.
E-mail address: hailin@sdau.edu.cn (H. Lin).

https://doi.org/10.1016/j.jff.2023.105520
Received 24 January 2023; Received in revised form 14 March 2023; Accepted 19 March 2023
Available online 29 March 2023
1756-4646/© 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
V.A. Uyanga et al. Journal of Functional Foods 104 (2023) 105520

supplements. However, the availability of a biodegradable material as a To the best of our knowledge, very few studies have reviewed the
suitable substitute for these additives presents a broad advantage for potential of chitosan in animal production, despite its multifunctional
exploration. roles and broad application. An understanding of the impacts of chitosan
Chitosan is an environmentally friendly material with promising and chitosan-based composites on gastrointestinal functions and animal
advantages in animal nutrition. Biologically, chitosan plays various health will significantly promote their utilization and adoption in the
functional roles, such as antimicrobial agents, biosensors, antioxidants, animal production sector. Therefore, this work provides comprehensive
drug delivery carriers, antitumor, hemostatic agents, anti-coagulants, research on the application of chitosan and chitosan-based composites
immunogenicity, and anti-cholesterolemic (Azeem et al., 2022; Maleki as feed additives for animal nutrition and further expounds on their
et al., 2022; Zou et al., 2019). In addition, chitosan and its derivatives mode of action, impacts on intestinal health, bio-carrier potentials, and
have been widely utilized in biomedicine and pharmaceuticals, textile the challenges bedeviling their applications.
industry, pulp and paper industry, food and beverage industry, bioen­
gineering and nanomedicine, cosmetology and biotechnology, agricul­ 2. Chitosan and chitosan-based composites
ture, and wastewater treatment (Batista et al., 2022; Crini, 2022;
Frigaard et al., 2022). The wide acceptability of chitosan has allowed for Chitosan is the second most abundant natural biopolymer after cel­
its fabrication into composite materials for various biological and agri­ lulose (Amirthalingam et al., 2021). It can be derived by deacetylation of
cultural applications (Ejeromedoghene et al., 2021). chitin, which is isolated from the shell of crustaceans (crabs and
Chitosan is edible and demonstrates significant nutritional potential shrimps) as well as the exoskeleton of insects and the cell wall of fungi
when incorporated as a feed additive (Singh et al., 2015). Thus, dietary (Adewuyi et al., 2019; Jacaúna et al., 2021). Structurally, chitosan
formulations containing chitosan and its associated composites have consists of N-acetyl-2-amino-2-D-glucopyranose and 2-amino-2-deoxy-D-
rapidly gained relevance in animal nutrition. Studies have demonstrated glucopyranose linked with β-(1–4) glycosidic bonds (Fig. 1) (Gadkari
their beneficial effects in improving growth performance, productivity, et al., 2022). Chitosan possesses functional amino (–NH2) and carboxyl
immunological responses, and suppressing intestinal microbial patho­ (–COOH) groups, which enables its interaction with other poly­
gens (Abdel-ghany & Salem, 2019). Interestingly, chitosan and chitosan- electrolytes and the generation of various complexes (Arya et al., 2017).
based materials have been extensively reported as potent antimicrobial Generally, chitosan in its native form is poorly soluble in aqueous
agents (Riaz Rajoka et al., 2020) against a wide range of microbes and alkaline media, which appears to limit its use in various applica­
(Table 1). Chitosan-supplemented diets provide a palatable alternative tions. The primary source of chitosan (e.g. crabs, shrimps, eggshells,
to antibiotics, alongside significant improvements to gut functions snail shells, fungi) is crucial for determining the type of chitosan ob­
(Nuengjamnong & Angkanaporn, 2018). These actions are directly tained, the molecular weight (10 – 1000 kDa), degree of solubility, and
related to their physicochemical properties such as low toxicity, avail­ degree of deacetylation (50 – 95 %) (Ardean et al., 2021). Interestingly,
ability, biocompatibility, biodegradability, mucoadhesion, permeation- chitosan derived from whole crab shells are more soluble than those
enhancing effects, non-antigenicity, and relatively low cost of produc­ from crab legs (Byun et al., 2013). However, low-molecular-weight
tion from natural sources (Jiménez-Ocampo et al., 2019; Ke et al., 2021). chitosan provides substantially higher antibacterial properties and
In addition, their drug-delivering properties have also been well estab­ good solubility when incorporated as liquid or solid foods (Younes &
lished, wherein they are utilized as vehicles for the efficient loading, Rinaudo, 2015). Chitosan with a high degree of deacetylation is more
targeted delivery, and controlled release of active substances to the promising with increased biological functions. Additionally, the
target sites (Hua et al., 2021; Zhang, Cai et al., 2020; Zhang, McClements sequence of the acetamido and amino groups in chitosan makes it
et al., 2020). accessible to other compounds for modification, further enhancing its
biological efficiency (Brasselet et al., 2019). To a large extent, these
properties play a major role in regulating the biological activity of the
Table 1 different chitosan-based materials (Teixeira-Costa & Andrade, 2021).
Selected applications of CMNCs. The primary amino or hydroxyl groups of chitosan can be modified
Chitosan metal-based Application References without interfering with the initial backbone to preserve its original
nanocomposites properties (Alli et al., 2021; Torkaman et al., 2021). In this way,
Copper chitosan nanocomposites Prevention of fungi (Abd-Elsalam modified chitosan is extremely relevant in terms of its modified deriv­
hydrogels contamination in dairy et al., 2020) ative. Numerous efforts have been made to create a variety of modified
cattle feed chitosan composites through trimethylation, etherification, cross-
Chitosan-silver nanocomposite Metagenomics analysis of (Udayangani
linking, graft copolymerization, esterification, carboxylation, carbon­
gut microbiota and immune et al., 2017)
modulation in zebrafish
ization, and so on (Aziz et al., 2019; Bakshi et al., 2020). Chitosan has
(Danio rerio) been modified or converted into salts and derivatives like chitosan
Chitosan-assisted glutamate, carboxymethyl chitosan, and hydroxypropyl trimethyl
Fe3O4@SiO2 magnetic Improved the health quality (Nasaj et al., ammonium chloride chitosan as well as chitosan nanocomposite
nanostructures functionalized of tested mice 2022)
matrices. These modifications tend to introduce new functional groups
with nisin
Chitosan capped with CuO It improved the mechanical (Javed et al.,
nanoparticles features of dental adhesive 2021)
Hydrothermally treated chitosan Used as a potential (Rajasekaran &
hydrogel loaded with copper micronutrient-based Santra, 2015)
and zinc particles antimicrobial feed additive

Gelatin-based nanocomposites Decreased the growth of (Amjadi et al.,

containing chitosan and ZnO
nanoparticles
inoculated bacteria in 2019)
chicken fillets and cheese.
Also, it controls the pH
values and color parameters
of chicken fillet and cheese
thereby improving their
quality

CMNC: Chitosan metal-based nanocomposites. Fig. 1. Chemical structure of chitosan.

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V.A. Uyanga et al. Journal of Functional Foods 104 (2023) 105520

into the chitosan skeleton and improve its functionality (Deng et al., Based on the targeted site of action, these actions can be classified as
2021; Li, Zhao et al., 2019; Li, Cheng et al., 2019). extracellular, intracellular, or both extra- and intracellular effects (Ke
Among these, chitosan oligosaccharide (COS) is an oligomer of chi­ et al., 2021). The antimicrobial activity of chitosan is attributed to their
tosan that is widely used in the livestock industry as feed supplements to induction of intracellular leakage and subsequent death of the micro­
promote productivity and gut functions. COS is derived from the enzy­ organisms (Kong et al., 2010). During contact between chitosan and
matic and chemical hydrolysis of chitosan, and they are non-toxic linear bacterial cell membrane, chitosan binds with the outer membrane
polysaccharides with a low degree of polymerization (Ayman et al., causing extensive cell surface alteration and loss of barrier function
2022). They have lower molecular weight, lower viscosity, higher water (Ardean et al., 2021). The positively charged chitosan binds to nega­
solubility, and higher bioactivity than chitosan (Abd El-Hack,El- tively charged bacterial phospholipid bilayer, altering their membrane
Saadony, Shafi, Zabermawi et al., 2020; Abd El-Hack, El-Saadony, permeability (via hydrolysis of peptidoglycans) which results in leakage
Shafi, Qattan et al., 2020). COS supplementation has been utilized for of intracellular components and cell death (Kong et al., 2010). Studies
various biological effects, such as anti-stressors, antibiotic alternatives, show that administering 0.30 % and 0.40 % dietary COS to young pigs
growth promoters, antioxidants, anti-inflammatory, gut protectant, and restricted the growth of harmful microorganisms (fecal E. coli and
immunomodulatory effects (Chang et al., 2020). Table 2 reports on some Clostridium spp.) (Han, Kwon, et al., 2007, Han, Yang, et al., 2007). In a
modified chitosan composites employed in animal production. subsequent experiment involving pig growers, dietary COS at 0.10 %
and 0.30 % enhanced immune system activity after Actinobacillus pleu­
3. Actions of chitosan and chitosan-based composites in animal ropneumoniae and Pasteurella multocida injections (Han, Kwon, et al.,
nutrition 2007, Han, Yang, et al., 2007). Chickens fed dietary COS also showed
weaker symptoms of salmonellosis and anatomopathological changes
The incorporation of chitosan-based composites in animal feed pro­ compared to the control groups (Balicka-ramisz et al., 2007). Essen­
motes activities such as antimicrobial, anti-oxidative, immunostimula­ tially, chitosan can suppress microbial growth via chelating essential
tory, hypocholesterolemic, and growth-promoting effects as metals, preventing extracellular nutrient uptake, altering cell perme­
summarized in Fig. 2. ability, and dysregulating RNA synthesis, protein synthesis, and mito­
chondrial function (Atay, 2020).
Furthermore, the utilization of chitosan in the diet of livestock spe­
3.1. Anti-microbial action of chitosan-based composites cies offers unique advantages over antibiotics, such as; i) prevention of
drug resistance in animals and humans; ii) improvement of intestinal
The anti-microbial action of chitosan-based composites has been health; and iii) an increase in ileal digestibility of dietary phosphorus
extensively studied over the years and is still accruing research interest. (Jin et al., 2020). Dietary COS supplementation limits antibiotics
administration and reduces drug resistance (Asadpoor et al., 2021). A
Table 2 study showed that COS and chlortetracycline administration reduced
Applications of modified chitosan composites in animal nutrition and health. intestinal inflammation and improved the growth of weaned piglets
Modified chitosan Effects of the modified References challenged with enterotoxigenic E. coli (Xiao et al., 2013). In another
composites chitosan composites study, feeding with 0.2 % COS declined Salmonella enterica/serovar
Chitosan oligosaccharide Enhances the growth (Chang et al., 2022;
Typhimurium (ST) colony-forming units in broiler chicks, indicating
performance, feed intake, Rusdi et al., 2021; that COS could be used in the control of ST contamination (Menconi
immune response, anti- Swiatkiewicz et al., et al., 2014). Therefore, it is evident that chitosan exerts potent anti­
oxidative, antimicrobial, and 2015) microbial activities by altering bacterial cell permeability and sup­
hypocholesterolemic
pressing microbial growth.
properties in swine and
poultry
Hydroapatite/collagen/ Restoration of defected (Rahman et al., 3.2. Antioxidant action of chitosan-based composites
chitosan composite maxillofacial mandible bone 2019)
Vanillic acid-grafted Facilitates the immune system, (Tejpal et al., 2017)
Free radicals are generated during the process of digestion, meta­
chitosan microspheres metabolic response, and
encapsulated with growth performance in bolism, or exposure to stressors (Kiran Kumar et al., 2022). Several
pyridoxine and experimental rats studies have shown that chitosan and its derivatives can attenuate
thiamine oxidative stress in animals. In laying hens, increasing levels of dietary
Mannan Oligosaccharide Improved serum copper level (Deniz et al., 2018) chitosan evoked a linear increase in plasma antioxidant capacity, which
in broiler
Chitosan and It improved the immune (Zhang et al., 2019)
diminished the yolk oxidant capacity of eggs (Farivar et al., 2018).
anisodamine efficacy of inactivated Similarly, the addition of COS (200 mg/kg) promoted the radical scav­
infectious spleen and kidney enging capacity, decreased inflammation, and restored the antioxidant
necrosis virus vaccine in capacity of Sprague Dawley rats challenged with hydrogen peroxide
Siniperca chuatsi
(Lan et al., 2019).
Chitosan graphene oxide It exhibited positive anti- (Feng et al., 2019)
nanocomposites interference property and Malondialdehyde (MDA) level is indicative of the degree of lipid
fairly accurate measurement peroxidation (Vasantrao Bhale et al., 2013). In a recent study, a
in real milk, thus ensuring that quadratic increase in the activities of glutathione peroxidase and total
the sensing platform can be superoxide dismutase, with lowered MDA levels was observed in laying
utilized for practical
applications, such as food
breeders fed with dietary chitosan at 250, 500, 1000, and 2000 mg/kg
inspection (Li et al., 2022). Thus, chitosan supplementation improved the serum
Alginate and chitosan Probiotics can be encapsulated (Fareez et al., 2015) antioxidant status in a dose-dependent manner. In another study, COS
encapsulation in alginate-chitosan supplementation (30 mg/kg basal diet) increased the plasma gluta­
composites to produce
thione peroxidase activity and upregulated the intestinal mRNA
functional ingredients
Selenium-Chitosan Se-chitosan could serve as a (Bami et al., 2021) expression of superoxide dismutase and glutathione peroxidase 1 (Xie
composite novel source of selenium and it et al., 2016). Evidently, chitosan ameliorates oxidative stress via its
enhanced the meat quality and actions to scavenge free radicals (Tamer et al., 2016), eliminate reactive
blood indices of broiler oxygen species (ROS), attenuate lipid peroxidation, and stimulate anti­
chickens.
oxidant enzyme activity (Ivanova & Yaneva, 2020).

3
V.A. Uyanga et al.
Fig. 2. Schematic illustration of the actions of chitosan and chitosan-based composites to modulate the biological and physiological responses of animals.
3.3. Immunostimulatory action of chitosan-based composites
Chitosan expresses potent immunostimulatory activity by initiating
the release of cytokines, chemokines, growth factors, and bioactive
lipids from immune cells (Fong & Hoemann, 2018). Chitosan is also
known to affect immune responses by increasing the serum levels of
immunoglobulins including IgM, IgG, and IgA (Li et al., 2016). It was
reported that the ability of chitosan to bind to bacteria or antigens ini­
tiates responses from the host’s defense system, and increases the total
leukocyte count (Nuengjamnong & Angkanaporn, 2018). More so, the
reactive amino and hydroxyl functional groups of chitosan act to acti­
vate macrophages, and induce antibodies and lysozymes, thus promot­
ing immunity.
In addition, dietary supplementation with COS exerts a significant
positive influence on the immune system. Dietary COS (30 mg/kg) fed to
sows and their offspring increased the IgM concentration in the colos­
trum and umbilical cord blood, as well as the IgG, interleukin 10, and
complement C (Duan et al., 2020). Moreover, compared to chlortetra­
cycline, COS exhibited a significant influence on immune system activity
by improving the weight of the immune organs (thymus, bursa cloacalis,
and spleen), promoting IgM secretion, stimulating macrophage activity
and inducing nitric oxide production (Deng et al., 2008). In growing
ducks, COS supplementation enhanced lymphocyte proliferation and
increased the weight of immune organs (Yuan Shi-bin, 2012). Also, an
increase in thymus weight with a simultaneous increase in IgG and IgM
contents was found in broiler chicks fed 30 mg/kg COS (Li, Zhao et al.,
2019; Li, Cheng et al., 2019). These beneficial effects of COS on immune
function occur since COS can modulate cytokine secretion, promote
lymphocyte counts and inhibit programmed cell death in immune
organs.
3.4. Hypocholesterolemic action of chitosan-based composites
Chitosan acts as a hypocholesterolemic agent due to its negative
effect on circulating adipocytokines, thus reducing lipid accumulation in
the muscle (Xu et al., 2014). In a comparative study, the introduction of
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Journal of Functional Foods 104 (2023) 105520
nano-powdered chitosan as against using commercial powdered chito­
san in a rat diet reduced the total low-density lipoprotein (LDL)-
cholesterol, and triacylglycerol contents but increased the high-density
lipoprotein (HDL)-cholesterol (Park et al., 2010). Also, chitosan’s
addition to rat diets demonstrated beneficial effects on cholesterol
metabolism by accelerating hepatic CYP7A1 activity, with an associated
decrease in plasma total cholesterol (Moon et al., 2007). Feeding with
chitosan elevates intestinal pH, and alters the metabolism of intestinal
bile acids. Fukada et al. (1991) reported that dietary chitosan fed to rats
decreased the serum cholesterol levels and increased both the colonic
and cecal pH levels. These changes altered intestinal bile acid compo­
sition and affected the intestinal conversion of primary bile acids to
secondary bile acids. Consequently, the fecal composition of lithocholic
acid and deoxycholic acid were increased, whereas 6β-isomer and 5-
epimeric 3α-hydroxy-6-keto-cholanoic acid and hyodeoxycholic acid
were decreased. Also, the cecal composition of lithocholic acid and α-,
β-, and ω-muricholic acids were increased, whereas, hyodeoxycholic
acid, 6β-isomer monohydroxy-monoketo-cholanoic acids, and 3 α, 6ξ,
and 7ξ -trihydroxy-cholanoic acid were decreased. Thus, the hypo­
cholesterolemic action of chitosan stems from its reduction of choles­
terol absorption and interference with bile absorption, although, the
mechanism of action remains unclear.
Similarly, COS has been shown to play a novel role in alleviating
lipid metabolism disorders. COS administration significantly decreased
the plasma total cholesterol and low-density lipoprotein (LDL) choles­
terol in the liver, bile, and feces of C57BL/6 mice, whereas, it increased
the hepatic protein expressions of CYP7A1, SR-BI, and LDL receptor in a
dose-dependent manner (Zong et al., 2012). Using obesity-associated
liver lipid metabolic disorders, in vitro and in vivo treatment of COS
ameliorated lipid accumulation, and suppressed the mRNA expression of
genes regulating glucolipid metabolism which was related to COS
reversal of PPARγ downregulation at the transcriptional and trans­
lational levels (Bai et al., 2018). It was also reported that dietary COS
reduced the blood serum content of VLDL cholesterol, LDL cholesterol,
triglyceride, and total cholesterol levels, thus improving the health
condition of broiler chickens (Ayman et al., 2022).
V.A. Uyanga et al.
4. Gastrointestinal tract (GIT) fate of chitosan-based composites
The GIT plays an important role in nutrient digestion and absorption,
and further acts as a barrier to external stimuli (Hao et al., 2012). Chi­
tosan forms a highly viscous solution in the GIT due to its melting
behavior in weak acid solutions. In vitro studies revealed that chitosan
becomes gel-like in artificial gastric juice solution, but doesn’t exhibit
such characteristics in artificial intestinal juice (Ruiz-Pulido & Medina,
2021). Digestive enzymes do not specifically hydrolyze chitosan; how­
ever, limited digestion may occur due to bacterial microflora and the
activities of digestive enzymes (Tabata et al., 2019). Owing to its limited
digestibility, chitosan exhibits the nature of dietary fiber.
Chitosan digestion in the gut is species-dependent since chickens
(hens and broilers) can efficiently degrade chitosan better than rabbits
after oral ingestion (Hirano et al., 1990). In the stomach, hydrogen ions
(H+) bind with the amino group (–NH2) of chitosan thereby forming a
cationic tertiary amino group (–NH+ 3 ). Thus, chitosan becomes a soluble
salt in the stomach environment where it interacts with hydrochloric
acid to form a cationic gel (Ahmadi et al., 2015). Anionic molecules such
as bile acids (lithocholic and cholic deoxycholic acid), fatty acids, fats,
and other lipids attach strongly to the NH+ 3 group of chitosan (De Aguiar
Vallim et al., 2013). Dietary chitosan limits micelle formation during
lipid digestion by bonding directly with acids, bile salts, fatty acids, and
lipids. This decreases fat deposition by increasing fecal lipid excretion,
limiting fat absorption in the intestine, and inhibiting triglyceride syn­
thesis (Liu et al., 2021). Thus, chitosan can alter emulsification by
binding sterols and cholesterol with hydrophobic bonds, giving rise to
large polymers that can be broken down during digestion (Panith et al.,
2016).
4.1. Impact of chitosan-based composites on nutrient digestibility
Chitosan promotes feed efficiency, nutrient utilization, digestibility,
and absorption (Henry, Gasco et al., 2015). In mid-lactating cows, chi­
tosan increased the dry matter (DM) and crude protein digestibility,
improved nitrogen and energy efficiency, and increased the concentra­
tion of milk polyunsaturated fatty acids (Del Valle et al., 2017). Also,
beef heifers fed 1 % chitosan (DM basis) with a low concentrate diet
showed an increased apparent total tract digestibility of nutrients
(Henry, Ruiz-Moreno et al., 2015).
Similarly, studies have also reported on the modulatory effects of
chitosan-based composites on the nutrient digestibility and growth
performance of animals. In broiler chickens, supplementing graded
levels of COS (0, 50, 100, 150 mg/kg) improved the feed efficiency, ileal
digestibility of nutrients, and growth performance of birds (Huang et al.,
2005). Studies with pigs showed that dietary COS improved body weight
gain, feed conversion ratio, apparent nitrogen, and nutrient digestibility
(Han et al., 2007). Beneficial effects of COS were found on the overall
performance of pig weaners, owing to its improvement of crude protein,
dry matter, phosphorus, and calcium digestibility, as well as increased
levels of amylase in the jejunum of weaners (Xu et al., 2014). In another
study, weaned pigs fed COS (2 g/kg diet) had enhanced growth per­
formance, improved total apparent digestibility of nitrogen and dry
matter, and decreased diarrhea occurrence (Zhou et al., 2012).
Evidently, COS promotes nutrient digestibility and growth performance,
although these effects may be dependent on the dosage administered
and the animal species studied. Importantly, COS improves protein
utilization by enhancing the absorption of amino acids (Yin et al., 2010),
and further acts as a prebiotic to favor the growth of beneficial bacteria,
thus improving gut health. Additionally, the growth-promoting effects
of chitosan have been associated with its improvements of feed utiliza­
tion, nutrient digestibility, and the release of growth factors such as
growth hormone and insulin-like growth factor 1 (Chen et al., 2009).
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Journal of Functional Foods 104 (2023) 105520
4.2. Impact of chitosan-based composites on rumen fermentation
The supplementation of chitosan to livestock feed largely influences
the rumen fermentation patterns of ruminants. Since ingested chitosan is
not degraded in the rumen, along with their antimicrobial activity, they
tend to act as ruminal fermentation modulators. Importantly, chitosan
can shift ruminal fermentation toward energetically efficient routes,
thus improving in vitro energy efficiency. Chitosan supplementation
effectively inhibited in vitro rumen biohydrogenation regardless of the
fat source by increasing trans-vaccenic acid and conjugated linoleic acid,
whereas, it decreased the saturated fatty acids (Goiri, Indurain et al.,
2010). Also, varying levels of dietary chitosan (0, 1625, 3,500, or 7,500
mg/kg DM) fed to Jersey cattle promoted their efficiency for nutrient
digestibility (Jacaúna et al., 2021). Therefore, these effects of chitosan
on rumen microbial fermentation are dose-dependent and largely
influenced by the chitosan’s properties and the nature of the ruminal
fluid.
Essentially, chitosan supplementation improves nutrient digestibility
and modifies ruminal fermentation without detrimental effects on ani­
mal health (Araújo et al., 2015). Soluble chitosan modifies ruminal
fermentation to promote propionate production while lowering
methane production and protozoal activity (Belanche et al., 2016).
Steers treated with varying doses of chitosan (400, 800, 1200, or 1600
mg/kg DM concentrate) showed linear increment in their DM and crude
protein (CP) total apparent digestibility, ruminal propionate content,
and the microbial CP production (Dias et al., 2017). Additionally,
feeding chitosan with whole raw soybean influenced the rumen propi­
onate contents, with modulatory effects on rumen fermentation (Dias
et al., 2020). These findings are associated with chitosan’s actions in
modifying the microbial ecosystem by negatively affecting the cellulo­
lytic bacteria, whereas, it favors fermentative activity in the gut (Goiri,
Oregui et al., 2010).
4.3. Impact of Chitosan-based composites on intestinal structure and gut
microbiota
The gut largely influences the health and physiological state of the
host (Mutuyemungu et al., 2023; Uyanga et al., 2021), and an alteration
in gut functioning would impact nutrient synthesis, digestion, absorp­
tion, and assimilation by the host (Wang et al., 2018). In piglets infected
with Escherichia coli, supplementation with nano chitosan–zinc complex
proved beneficial to the gut digestion and absorption, as well as the
intestinal antioxidant capacity via its stimulation of carbohydrate
digestive enzymes (such as amylase, sucrose, maltase, and lactase),
upregulated jejunal gene expression of nutrient transporters (SGLT1,
GLUT2, PEPT1, and EAAC1) and increased jejunal contents for gluta­
thione, T-SOD, and GSH-Px (Zhang et al., 2021). Importantly, chitosan’s
actions to influence the bioavailability of antioxidants in the gut directly
affect the microbiome, since the interactions between antioxidants and
the gut microbiota help diversify gut bacteria, as well as promote the
production of bioactive metabolites in the gut (Naliyadhara et al., 2023).
As a functional ingredient, chitosan and its derivatives can influence
intestinal immunity. Chitosan supplementation downregulated jejunal
IL-17 expression, inhibited the mTOR pathway, and lowered the Fir­
micutes to Bacteroidetes ratio, thus altering the intestinal microbiota in
mice (Xiao et al., 2016). In another study, COS supplementation alle­
viated intestinal inflammation and promoted cell-mediated immunity in
pigs challenged with Escherichia coli via reducing the diarrheal fre­
quency, upregulating IL-1β and IL-6 mRNA expression, and further
increasing the abundance of calprotectin and TLR4 protein expression in
the jejunal mucosa (Xiao et al., 2014). Co-administration of chitosan and
type II collagen upregulated the mRNA expression for TGF-β, IL-4, and
IL-10, but downregulated IL-2 expression in Peyer’s patches of mice,
thus promoting an anti-inflammatory response (Porporatto et al., 2004).
COS also proved beneficial in alleviating intestinal inflammation and
promoting mucosal repair by suppressing the levels of TNF-α, IL-1β, and
V.A. Uyanga et al. Journal of Functional Foods 104 (2023) 105520

IL-6 in the serum and colon, downregulating TLR4, NF-κB, STAT3, and
pSTAT3 colonic expression and enhancing gut microbiota diversity in
dextran sodium sulfate-induced ulcerative colitis mice (Guo et al.,
2021). Therefore, the biological activity of chitosan on intestinal im­
munity is explicitly associated with the ability of chitosan to promote the
synthesis of regulatory cytokines, IgA production, and lymphocytes to
maintain intestinal homeostasis (Moine et al., 2021).
Chitosan also plays a crucial role in maintaining intestinal structure
and improving gut morphology and integrity (Ibitoye et al., 2019). It
acts to improve the morphology of the small intestinal segments, thus
promoting feed efficiency and body growth (Yang et al., 2022). Broiler
chicks fed with dietary chitosan (0.6 g/kg of diet) had significant
morphological changes in the intestinal tract such as hypertrophied villi,
cell clusters, increased duodenal cell mitosis, and larger ileal villi area,
ultimately improving the growth performance of birds (Khambualai
et al., 2009). COS elicits dose-dependent responses on the villus height
(VH), crypt depth (CD), and villus height to crypt depth (VH: CD) ratio,
thus promoting the population and size of intestinal glands (Ayman
et al., 2022). In piglets infected with Escherichia coli, COS supplemen­
tation effectively increased the VH, VH/CD, number of goblet cells,
intraepithelial lymphocytes, and the protein expression of occludin and
sIgA, thus improving the intestinal barrier function (Xiao et al., 2014).
In addition, COS directly influences the intestinal microbial com­
munity of the host (Hu et al., 2020). The impacts of dietary COS on gut
microbiota and intestinal structure are summarized in Table 3. In dia­
betic mice, COS treatment alleviated gut barrier damage, restored
glucose metabolism, and modulated the gut microbiota (Zheng et al.,
2018). Dietary COS influenced the cecal microflora population of pig
weaners by promoting a higher population of Bifidobacteria and Lacto­
bacilli, but lowered the Staphylococcus aureus population (Yang et al.,
2012). In high-fat diet mice, chitosan intervention modified the intes­
tinal microbiome by increasing Coprobacillus cateniformis and Clos­
tridium leptum species, whereas, it decreased Clostridium
lactatifermentans and Clostridium cocleatum (Tang et al., 2020). A recent
review had surmised that chitosan and COS improve intestinal health via
their actions to promote Bifidobacteria and Lactobacilli spp, alleviate
intestinal inflammation, promote tight junction protein expressions,
minimize lipids absorption, and their regulation of intestinal microflora
during health and disease conditions (Chen et al., 2022). Essentially,
COS encourages the proliferation of useful bacteria while limiting the
growth of pathogenic bacteria in the gastrointestinal tract. Summarily,
the actions of chitosan and chitosan-based composites on various aspects

Table 3
Impacts of dietary chitosan and chitosan-oligosaccharides (COS) supplementation on intestinal integrity, and gut health of animals.
Chitosan form and Properties Animal Study Major findings References
dosage model period
(days)

100 mg/kg Chitosan N/A Weaned 21 Decreased colon and caecal E. coli population and enhanced ileal (Wan et al.,
pigs Bifidobacterium count 2017)
1000 ppm of prawn D.A: 15 % Pig 63 Lowered count of phylum Firmicutes in the colon and Lactobacillus spp. (Egan et al.,
shell chitosan A.M.W: 124,000 ± 10,000 count in both the caecum and colon and increased caecal Bifidobacteria 2015)
g/mol. count
0.5 g/kg Chitosan A.M.W: 1000 Da Weaned 14 Increased ileal and caecal microbial count of Faecalibacterium (Kong et al.,
DD: 95 % pigs prausnitzii, Lactobacillus spp, Bifidobacterium spp, and Bifidobacterium 2014)
Water solubility: 99 % breve,
0.2 % Chitosan DD: 95 % Broilers 10 Reduced colony-forming units of Salmonella enterica in broilers during (Menconi et al.,
M.W: 350 kDa in vitro and in vivo trials 2014)
Viscosity: 800 mPa
100, 500, 1,000 and DD: 85.09 % Weaned 28 Quadratic increase in the ileal and jejunal villus heights, and VD:CD of (Xu et al., 2013)
2,000 mg/kg Viscosity: 45 cps pigs the duodenum, ileum, and jejunum
Chitosan
200, 400, 600 mg/kg COS contained 30 % COS Weaner 14 Increased caecal concentration of Lactobacilli and Bifidobacteria and (Yang et al.,
COS and 70 % cyclodextrin as a pigs lowered caecal count of S. aureus 2012)
carrier.
A.M.W: 1,500 Da; Water
solubility: 99 %.
150 mg/kg COS + 300 M.W: 1 kDa Pigeon 7 to 25 Provides beneficial effects on the gut health, improves the growth (Wen et al.,
~ 400 mg/kg C. DD: 85 %~90 %. squabs performance and intestinal health of early-weaned pigeon squabs 2022)
butyricum
100 or 150 mg/kg COS N/A Broiler 20 Increased body weight, weight gain, and carcass weight; while feed (Ahmed et al.,
and 0.57–1.02 % conversion ratio decreased with increased supplemental levels of diet 2021)
Valine
75, 150 or 225 mg/kg DD: 90 % Piglets 56 Increased nutrient absorption, digestibility efficiency, and improved (Suthongsa
COS A.M.W: 7.5 kDa. gut functioning via elongated villi with increased enterocyte numbers. et al., 2017)
150 mg/kg COS i. Low MW: 8 kDa + DD: Weaning 56 COS having 8 kDa M.W and ~ 90 % DD proved most effective to (Thongsong
~90 % pigs promote feed intake, nutrient digestibility, and intestinal absorption. et al., 2018)
ii. Medium MW: 65 kDa +
DD: ~80 % or ~ 90 %
5 or 20 mg COS in ovo N/A Fertile 21 Increased polysaccharide-utilizing bacteria such as Lactobacillus (Zhang et al.,
injection eggs johnsonii, Bacteroides coprocola, and Bacteroides salanitronis and 2020)
enriched metabolic pathways including gluconeogenesis, L-histidine
biosynthesis, and fatty acid biosynthesis.
200 mg/kg/d COS DD: 88 % Mice 90 COS reshaped the microbiota and relieved gut dysbiosis in diabetic (Zheng et al.,
M.W: < 1 kDa model mice by promoting Akkermansia and suppressing Helicobacter spp 2018)
300; 600; 1000 mg/ A.M.W: < 1000 Mice 21 Improved colonic histology, decreased intestinal inflammation and (Mohyuddin
kg/day Chitosan DD: > 90 % model increased the expression of tight junction proteins in heat stressed et al., 2021)
mice
0.6 g/kg chitosan DD: 90 % Broilers 35 Increased duodenal cell mitosis, ileal villus area, hypertrophied villi (Khambualai
and epithelial cells et al., 2009)
300 mg/kg COS M.W: <5000 D Piglets 21 Increased the villus length, villus length/crypt depth, and goblet cells, (Xiao et al.,
DD: 90 % but lowered the villus width, crypt depth and reduced intestinal 2013)
inflammation.

N/A: Not available; DD: Degree of deacetylation; DA: Degree of acetylation; A.M.W: Average molecular weight; M.W: Molecular weight.

6
V.A. Uyanga et al.
of intestinal health are depicted in Fig. 3.
5. Application of chitosan and chitosan-based composites as
biocarriers for substance delivery
Although bioactive ingredients such as essential oils, vitamins,
polyphenols, microbial feed additives, and antioxidant agents possess
several health benefits, their application is limited because they often
have poor bioavailability, rapid release time, chemical instability,
possess relatively low solubility, are susceptible to oxidative degrada­
tion, or may have an unpleasant taste (Kurek et al., 2022; Tolve et al.,
2021). Therefore, the use of biological composites in the form of nano-
capsules, microbeads, and nanogels (Fig. 4) to protect these bioactive
ingredients or compounds has gained significant interest in the livestock
industry (Table 4).
5.1. Chitosan-based composites for essential oil delivery
Essential oils (EO) are one of the important bioactive components
Fig. 3. Illustration showing the impacts of chitosan-based composites on the intestinal structure, microbial composition, rumen fermentation, and nutrient di­
gestibility of animals.
7
Journal of Functional Foods 104 (2023) 105520
used in the livestock industry. They are organic compounds obtained
naturally from several plants, spices, and herbs, such as garlic, ginger,
basil, rosemary, cloves, cumin, mustard, cinnamon, thyme, mint, cori­
ander, etc. Often classified as phytogenic feed supplements, they usually
contain mixtures of volatile and aromatic compounds at specified ratios
and have a wide variety of bioactive characteristics (Salehi et al., 2020;
Stevanović et al., 2018). Such properties include making the feed more
palatable, enhancing the functionality of the digestive system,
improving the gastrointestinal structure and microbial flora, increasing
antioxidative and antimicrobial potential, and enhancing the production
efficiency and quality of livestock products (Baptista-Silva et al., 2020;
Sharifi-Rad et al., 2017). However, their potency and functionality could
be compromised by direct integration into animal feed because they are
hydrophobic, highly volatile, and have low thermal stability (Rao et al.,
2019). This nature of EO makes them easily degradable through crys­
tallization, oxidation, enzymatic deterioration, or hydrolysis during
passage through the gastrointestinal tract or when stored (Kyriakoudi
et al., 2021). To a large extent, this can impair their natural flavor,
reduce solubility, and negatively impact their biological activities.
V.A. Uyanga et al.
Fig. 4. Various forms of Chitosan-based composites used in delivering bioactive compound to animals.
Hence, the effect of most EO on feed’s organoleptic properties remains a
problem and it is seen that EO efficacy increases when administered to
animals in a protected or encapsulated form (Turek & Stintzing, 2013).
Therefore, using biological polymers as EO carriers before supple­
menting in animal feed is considered an effective alternative, which
allows blends containing different EOs to be used. Recently, encapsu­
lation methods to increase the properties of EOs have received
tremendous attention, and biopolymer-mediated encapsulation has
received the most focus.
The effects of administering EO that has been encapsulated with
other protective materials to poultry, ruminants, and pigs have been
reported (Favaretto et al., 2020; Spanghero et al., 2009), but loading EO
into chitosan for animal food supplements is still a developing tech­
nology. Chitosan molecules were successfully loaded with guava leaves
EO using a two-step nanoencapsulation process involving oil-in-water
emulsification and ionic gelation by electrostatic interaction (Zhang,
Cai et al., 2020; Zhang, McClements et al., 2020). They reported that
chitosan in the form of nanogels loaded with EO was ideal because it had
greater entrapment effectiveness, stability, and controlled release. In
another study, nano-chitosan was encapsulated with garlic EO as a
substitute for antimicrobials in broiler’s diet (Amiri et al., 2020). The EO
was encapsulated into a chitosan composite by ionic gelation. Compared
to garlic EO in free form, the chitosan-coated garlic EO was more active
against Escherichia coli. The chitosan-loaded garlic EO positively
impacted the antioxidant activity in vitro and further decreased oxida­
tive degeneration caused by free radicals in broiler’s meat. Also, the
efficacy of the EO on growth performance was enhanced probably due to
the positive charge carried by chitosan that tends to bind easily with the
oil, thereby increasing the chances of protecting the loaded compound
from being easily degraded by the gastrointestinal acid and protease
(Sawtarie et al., 2017). It is understood that chitosan nanocapsules can
bind the oils and gradually release their contents into the gastrointes­
tinal cells, thus improving their absorption while retaining the EO
properties (Sundari et al., 2013). Additionally, the antibacterial prop­
erty of nano chitosan and the synergy between the protective layer of the
nanoparticle and the EO’s antimicrobial property was crucial in
reducing the population of pathogenic bacteria in the chick’s GIT, since
it fostered the proliferation of the beneficial microbes (Nouri, 2019).
8
Journal of Functional Foods 104 (2023) 105520
5.2. Chitosan-based composites for vitamins, minerals and amino acids
delivery
Delivering micro-nutrients like vitamins and trace elements to live­
stock is important for optimum health and production. Vitamins are
mostly encapsulated to increase their shelf life, protect them from being
impaired during processing such as pelleting or extrusion, storage, and
transport, and most importantly, to ensure they are safely delivered to
the target site without rapid response degradation, especially in rumi­
nants where rumen microbes are present. Improved dairy cow produc­
tivity has been attributed to rumen-protected choline. For instance,
rumen-protected choline can help increase the amount of milk and
milk choline concentration during early lactation in cows (Jayaprakash
et al., 2016).
Vitamin C is another essential nutrient required to maintain physi­
ological processes. However, it is extremely sensitive to light, heat, and
air. Therefore, vitamin C can be encapsulated with chitosan before it is
supplemented into livestock diets or subjected to thermal processing to
avoid the direct impact of environmental effects and prolong its shelf
life. Studies have encapsulated vitamin C in chitosan nanoparticles with
varying diameters to extend its shelf life and they further investigated its
delivery into the biological system. It was reported that chitosan nano­
particles prolonged the duration of vitamin C residence in the digestive
tract of rainbow trout (Alishahi et al., 2011). The release time of vitamin
C was extended by 12 h, probably attributable to the mucoadhesive
characteristics of chitosan. For micronutrients, a multi-micronutrient
delivery system of copper and riboflavin was developed using chitosan
microbeads, and its suitability as a cattle feed additive was examined
(Duffy et al., 2018). Using a simulated rumen fluid to mimic the salt
concentration and pH of the rumen environment, there was a controlled
release of riboflavin under the in-vitro rumen condition and a sustained
release of about 60 % copper in the simulated abomasum over 3 h. In
another study, administering 100 mg/kg of copper-loaded chitosan
nanoparticles enhanced the growth performance, immune status, gut
microbial community, and protein synthesis in broiler chickens (Wang
et al., 2011). Likewise, in weaned piglets, copper-loaded chitosan
improved the growth performance, reduced the rate of diarrhea, and
modified the microflora and morphology of the intestine (Wang et al.,
V.A. Uyanga et al. Journal of Functional Foods 104 (2023) 105520

Table 4
Chitosan-based composite for bioactive component delivery in animals.
Chitosan form Animal Delivered bioactive Animal responses References
component

Nano-encapsulated chitosan
Chitosan-tripolyphosphate
nanoparticle
Nano-encapsulated chitosan
Chitosan nonoparticle
Chitosan microbeads
Chitosan nanoparticles
Chitosan nonnoparticles
Chitosan/alginate nanofiber
Chitosan/alginate nanofiber
Chitosan-based microsphere
Chitosan nanoparticle
Chitosan nanoparticles
Chitosan nanoparticles
Chitosan nanoparticles
Chitosan
Chitosan nanoparticles
Chitosan (CS)–dextran sulfate
(DS) nanoparticles
Sodium alginate-chitosan
Chicken Garlic essential oil • Enhanced EO activity against E. coli bacteria (Amiri et al., 2021)
• Influenced antioxidant capacity of broiler
• Reduced oxidative deterioration of meat
• Improved growth performance
Broiler chickens Cummin essential oil • Increased growth performance (Amiri et al., 2020)
• Improved mucin 2 gene expression
• Lowered triglyceride level in chicken blood
• Improved chicken immune response
Broiler chickens Mint, thyme, and cinnamon • Improved body weight gain and feed conversion ratio (Nouri, 2019)
essential oil • Enhanced the effects of the essential oils
• Improved immune response
Broiler chicks Tumeric extract • Elevated true metabolizable energy (Sundari et al., 2013)
• Increased feed efficiency
• Increased intestinal lactobacilli
Cattle Copper and Riboflavin • Controlled release of micronutrients in the abomasum (Duffy et al., 2018)
Broiler chickens Copper • Improved growth performance and improved immunity (Wang et al., 2011)
• Improved gut microbiome
• Enhanced protein synthesis
Piglets Copper • Improved growth performance (Wang et al., 2012)
• Lowered frequency of diarrhea
• Altered intestinal microbiome and morphology
Ruminant Lactobacillus acidophilus • Protected probiotic from gut acid and salt degradation (Chang, Liu et al.,
probiotics • Preserved and improved number of bacteria cells delivered to 2021)
the gut
Ruminant Lactobacillus acidophilus • No changes in rumen fermentation and rumen bacteria profile (Chang, Lambo et al.,
probiotics 2021)
Sheep Nasal vaccine against ovine • Induced systemic and local antibodies (Díaz et al., 2016)
brucellosis
Broiler chickens Salmonella vaccine • No adverse effect on production performance (Acevedo-Villanueva
• Induced immune response against Salmonella et al., 2020)
• Mitigate Salmonella enteritidis colonization in bird’s caecum
Broiler chicks ΦKAZ14 bacteriophage • Reduced bacterial colonization of the chicken intestine (Kaikabo et al., 2017)
against colibacillosis • Enhanced bacteriophage therapy
White Leghorn DNA vaccine • Induced effective immune response against Campylobacter (Huang et al., 2010)
chickens jejuni infection
Pigs Inactivated swIAV vaccine • Augmented cross-reactive T and B lymphocyte response at (Dhakal et al., 2018)
mucosal and systemic sites
Broiler chickens Selenium • Inclusion of Se-chitosan improved the immune response, in­ (Khajeh Bami et al.,
testinal microflora, and intestinal histomorphology 2022)
Pigs Chromium • Beneficial effects on the growth, carcass characteristics, and (Wang et al., 2014)
meat quality
• Positively effects on lipid catabolism
Rabbit GnRH analogue • Improved the acrosome integrity of sperm cells (Fernández-Serrano
et al., 2017)
Broiler chickens Probiotic strain, • Positive effects on appetite (Trabelsi et al., 2016)
Lactobacillus plantarum TN8 • Lowered the cholesterol and triglyceride contents

2012). livestock performance and growth, maintaining a balanced abundance

In the case of amino acids, they are mostly supplemented in a rumen-
protected form for ruminant nutrition. This allows them to transit
through the rumen until delivered to the target site in the abomasum or
intestine, where they would be degraded and can exert the best effects,
further improving amino acid utilization in animals. Rumen-protected
amino acids (such as lysine and methionine) have been protected
either mechanically or physically to prevent rapid degradation by
ruminal microorganisms or acidic conditions in the gut (Wei et al.,
2022). Following the coating preparation, rumen-protected amino acids
sustain lengthy retention in the rumen with little amino acid disap­
pearance and a quick release time in the abomasum. Reports show that
chitosan coating for rumen bypass amino acids enhances their stability
in the simulated rumen conditions while increasing the integrity of the
amino acid at body and room temperature, hence allowing for its suc­
cessful delivery to ruminants in a viable state (Mazinani et al., 2020).
5.3. Chitosan-based composites for probiotics delivery
Probiotics are live microorganisms that provide health benefits when
administered in sufficient quantities. In animal production, they are
recognized for their beneficial effects, which include enhancing
of the gut microflora, improving intestinal health, and immunomodu­
lation (Lambo et al., 2021). Oral administration of probiotics is not
without its limitations because of the complex and acidic environment of
the gastrointestinal tract. Chances are that the protein could be dena­
tured, the cell wall disrupted, and the cell membrane damaged due to
the different digestive enzymes, pH, and high bile salt concentration
(Chang, Liu et al., 2021). These would alter the population and activity
of microbial probiotics, causing insufficient viable microbial cells to
reach the targeted site for colonization (Vaziri et al., 2018).
Encapsulation of probiotics in biological composites increases their
stability during processing and when stored. This helps to prevent mi­
crobial cell degradation and maintain their viability during passage
through the mouth to the gut of both monogastric and ruminants, where
they exert the most effect (Natsir et al., 2019). The use of chitosan-based
composites to deliver probiotics to target sites in animals is still at an
emerging phase. In an in vitro study, Lactobacillus acidophilus was loaded
into chitosan/alginate nanofiber microcapsules through electrostatic
spinning (Chang, Liu et al., 2021). The study demonstrated that
L. acidophilus was protected when exposed to high bile salt concentra­
tions and varying gut pH conditions. At the same time, the bacterial cell
count was preserved. In a similar work, chitosan/alginate microcapsules

9
V.A. Uyanga et al.
loaded with L. acidophilus were successfully delivered to the simulated
ruminal intestinal site without negatively altering rumen fermentation
and bacterial profile (Chang, Lambo et al., 2021). A probiotics-chitosan-
based composite could be the potential alternative to antimicrobial
growth promoters for livestock use because the chitosan component
would serve as a barrier to the rapid destruction of the live microor­
ganism while promoting their controlled release for optimum
effectiveness.
5.4. Chitosan-based composites for drug and vaccine delivery
Chitosan is a functional biological polymer with significant anti­
bacterial and anti-biofilm properties. There are several reports of chi­
tosan as a molecular carrier in drug delivery since it can successfully
deliver to target sites, and improve drug properties and effectiveness
against various infections (Zhao et al., 2018). Thus, chitosan can be
modified for the efficient delivery of various drugs, nucleic acids, and
proteins (Chen et al., 2019). Studies show that chitosan can be incor­
porated with some reproductive hormones to improve their bioavail­
ability, permeability, biological half-life time, and stability (Fernández-
Serrano et al., 2017). Nanofabrication of GnRH-loaded chitosan-TPP
nanoparticles improved the ovarian activity and reproductive perfor­
mance of anestrus dairy buffaloes during the low breeding season
(Gallab et al., 2022). Similarly, the administration of GnRH–loaded
chitosan nanoparticles to rabbits was beneficial in reducing the con­
ventional dosage of GnRH by half during intramuscular injection,
without altering fertility (Hassanein et al., 2021). As such, the use of
chitosan provides a better approach for livestock drug delivery since
their biocompatibility and biological activity allow for easy absorption
into the body. The application of chitosan microneedles patches was
reported to be suited for the transdermal delivery of meloxicam (a sys­
temic analgesic) after routine procedures in cattle (Castilla-Casadiego
et al., 2021). This finding accrues animal welfare benefits, allowing for
the long-term supply of analgesia during pain management.
Additionally, due to their characteristics as positively charged
biocompatible polymers and natural mucoadhesive properties, chitosan-
derived nanoparticles have been used extensively to administer vaccine
antigens to livestock, particularly through the mucosa (Cho et al., 2021).
Chitosan and liposome nanoparticles were synthesized as adjuvants for
the co-delivery of a commercial pneumococcal conjugate vaccine (PCV)
in mouse models (Haryono et al., 2017). The co-delivery of these
nanoparticles elicited immunogenic properties by stimulating the
immunoglobulin G subclass of antibodies, further promoting the utili­
zation of chitosan as a biomaterial for drug/vaccine delivery in humans
and animals. Since there are various drawbacks to delivering vaccine
antigens in their natural state, including their toxicity, ease of degra­
dation, and poor immunogenicity (Sridhar et al., 2015), chitosan-based
composites have been extensively used to deliver mucosal vaccines
against bacterial and viral infections, especially to poultry and pigs
(Renu & Renukaradhya, 2020). To prevent ovine brucellosis in lambs,
spray-dried chitosan-based microspheres tested as a carrier for nasal
mucosa vaccination in polymeric antigen were found to successfully
initiate systemic and local antibodies during intranasal immunization
(Díaz et al., 2016). Similarly, chitosan-based vaccines have been used to
deliver the antigens for infectious bronchitis virus (Lopes et al., 2018),
avian influenza virus (Hajam et al., 2020), swine influenza virus (Dhakal
et al., 2018), Salmonella enteritidis (Acevedo-Villanueva et al., 2020),
Escherichia coli (Kaikabo et al., 2017), and Campylobacter jejuni (J. Huang
et al., 2010). Chitosan is also used to deliver vaccine antigens orally
because of its biodegradability property (Xing et al., 2018). As an
alternative to systemic vaccines, oral administration of vaccines is crit­
ical to animal welfare because it prevents animal hide and carcass
damage and the problem of restraint and handling (Hoelzer et al., 2018).
10
Journal of Functional Foods 104 (2023) 105520
5.5. Chitosan-based composites for flavors delivery
Flavors and aromas play an important role in livestock feeding and
palatability because animals depend on their senses of smell and taste to
assess feed palatability. Feedstuffs with undesirable odors or tastes could
result in reduced feed intake and poor performance. The adoption of
feed flavors in the livestock industry aims to improve the aroma and
taste of livestock feeds and hence promote feed intake, digestibility,
efficiency, and productivity. Also, in case of changes to the feed
formulation, flavors prevent animals from rejecting the feed. Flavoring
agents used in livestock feed could be organic like garlic, anise, and
black cumin, or artificial such as fruit extracts and chemical products,
including vanillin, sodium glutamate, etc. It was observed that a com­
mercial flavor that imparts red fruit and vanilla flavor to the feed of
multiparous sows increased the amount of feed intake and enhanced
sows’ performance under tropical conditions (Silva et al., 2021). Many
of these substances are given as free-flowing, non-electrostatic concen­
trations in dry powdered form and can be added to feed as a premix
along with other trace ingredients.
However, in recent years, encapsulating liquid or solid substances
with composite materials has made it possible to control and target
release, mask the taste, prevent incompatible substances from interact­
ing with each other in the product matrix, protect bioactive compounds
from oxidation promoters (like light, air, and metals), and to enhance
the degree of resistance to thermal process during manufacturing (Grgić
et al., 2020). Different studies have successfully used chitosan-based
composite in the food processing industry as a carrier for fragrances
and flavors. For example, the encapsulation of peach flavor in water-
soluble chitosan by spray drying has been explored (Estevinho et al.,
2013). Likewise, liquid smoke and thymol were encapsulated in elec­
trospun chitosan nanofiber to improve the quality of sea bass fish fillets
(Ceylan et al., 2018). Still, the use of chitosan and chitosan-based
composites as a flavor or aroma carrier in animal feed is yet to be
fully explored.
6. Challenges to the utilization of chitosan and chitosan-based
composites for animal production
The use of bioactive substances including chitosan and chitosan-
based composites attracts global concern due to their broad applica­
tion and enormous beneficial uses. However, this also creates a knowl­
edge gap as chitosan and its derivatives need to be extensively
investigated across various fields of application (Abd El-Hack, El-Saad­
ony, Shafi, Zabermawi et al., 2020; Abd El-Hack, El-Saadony, Shafi,
Qattan et al., 2020; Jiménez-Ocampo et al., 2019). Chitosan is widely
regarded as a non-toxic, biodegradable, and biocompatible polymer.
However, modifications to the chitosan molecule may influence its
pharmacokinetic properties and toxicity. Studies have demonstrated
that chitosan exerts concentration- and molecular weight-dependent
cytotoxicity (Wiegand et al., 2010; Narvaez-Flores et al., 2021). In
Caco-2 cells, treatment with chitosan malate either as a solution or as
microparticles exerted dose-dependent effects, such that the cell
viability and cytoskeletal structures were modified, especially at high
concentrations (Juliano et al., 2011). In another study, chitosan solution
and chitosan-coated liposomes administered to a TR146 cell line
decreased cell viability especially at higher concentrations compared to
other polymers (Klemetsrud et al., 2018). A recent elucidation on the
cytotoxicity of chitosan also affirmed that chitosan nanoparticles
expressed low cytotoxicity regardless of the chitosan derivative, particle
composition, cytotoxicity assay, cell line, and animals used for experi­
mentation (Frigaard et al., 2022). Essentially, it is realized that chitosan
toxicity is dependent on the concentration, degree of deacetylation,
charged density of the molecule, and its molecular weight.
In a detailed review by Kean and Thanou (2010), in vivo studies using
chitosan also reported minimal toxic effects. In an explorative study
conducted by the National Toxicology Program, male and female
V.A. Uyanga et al.
Sprague Dawley rats were fed 1 %, 3 %, and 9 % dietary chitosan for 6
months. It was found that rats fed with high levels of chitosan had
decreased phosphorous, cholesterol, and triglycerides contents, and
lowered percentage fat digestion. Furthermore, feeding with 3 % and 9
% chitosan significantly lowered the serum concentrations of vitamin A
and vitamin E, decreased the hepatic vitamin E levels, and reduced the
absolute and relative weights of the liver and thymus (National Toxi­
cology Program, 2017). These findings suggest that the consumption of
high levels of chitosan may pose detrimental effects on the metabolic
and physiological responses of animals. Therefore, considering the
extensive variations in composition and rapid development of chitosan-
based composites, it is important to perform an in-depth evaluation on
the safety of novel chitosan derivatives before application. More so, it is
recommended that the minimum safe concentrations of chitosan should
be applied for desirable effects.
In animal production, chitosan and chitosan-based composites have
been largely used as feed supplements for both monogastric and rumi­
nant animals to elicit various biological effects. This necessitates an
extensive examination to elucidate their suitability, reactivity, utiliza­
tion, and resultant effects, especially in food animals. Howbeit, some
challenges limiting the practical applications of chitosan include; (i)
chitosan may interact with functional diverse components in the food
matrix; and (ii) the stability of chitosan poses a major challenge to its
adoption and incorporation for other purposes (Abd El-Hack, El-Saad­
ony, Shafi, Zabermawi et al., 2020; Abd El-Hack, El-Saadony, Shafi,
Qattan et al., 2020). Some studies have also reported on the adverse
effects of chitosan and chitosan-based composites in animals. It was
found that adding both chitosan and soybean oil to the diet of dairy cows
compromised their growth performance, and decreased the milk yield,
nitrogen use, and feed conversion efficiency possible due to negative
interactions between the feed ingredients (Del Valle et al., 2017). In
another study, chitosan exerted negative effects on the rumen ciliate
protozoa population in animals fed high forage diet, and chitosan
combined with rapeseed oil negatively affected the rumen ciliate,
Dasytricha ruminantium in maize silage diet (Wencelová et al., 2014).
The anti-protozoan effects of chitosan although potentially useful
(Belanche et al., 2016), may also prove harmful where it harms the
rumen bacteria with a consequent decline in dry matter digestibility. In
addition, treatment of rabbits with GnRH–loaded chitosan nanoparticles
was reported to negatively affect fertility since it induced the sustained
release of GnRH for a longer period, extending the ovulation time, ul­
timately resulting in asynchrony in ova release and variation in embryo
developmental stage (Hassanein et al., 2021).
Considering their biological properties and broad application, it is
deemed that the functional attributes of chitosan directly outweigh the
challenges limiting its application. From the extensive discourse pre­
sented in this work, it is surmised that chitosan and chitosan-based
composites exert significant beneficial roles to the gastrointestinal
health of animals. This includes their alleviation of intestinal inflam­
mation, boosting intestinal antioxidant capacity, promotion of nutrient
metabolism, increasing nutrient digestibility, regulation of rumen
fermentation, improvement in intestinal barrier functions, and regula­
tion of intestinal microbial community. Altogether, it is evident that
further evaluation is necessary to access and characterize the distinct
properties, and applicability of chitosan and chitosan-based composites
to ensure their successful application.
7. Conclusion
With the increasing knowledge of biotechnology, chitosan has been
fabricated together with other bioactive substances into various bio­
composites, which opens up a broad range of chitosan-based alternatives
and utilization in various fields of application. In this work, we have
presented up-to-date knowledge on the applications of such chitosan-
based composites in animal production. Significant achievements have
been recorded in the application of chitosan in animal production and
11
Journal of Functional Foods 104 (2023) 105520
reports have pointed to its beneficial effects in promoting growth per­
formance, reproductive performance, nutrient utilization efficiency, gut
health, digestive physiology, anti-microbial responses, and the overall
health of animals.
However, future works should aim at exploring the synergistic and/
or antagonistic effects of chitosan with other bioactive substances
especially those used in feed formulation. This would help provide in­
formation and clarify their effects on different animal species, the
optimal inclusion levels, and their mode of action, thus facilitating the
utilization of chitosan and chitosan-bioactive composites for animal
production purposes. The knowledge on chitosan keeps evolving, as
such, extensive studies are necessary to develop analytical protocols for
quality assessment and to optimize its utilization before application.
Further research investigating different chitosan sources, doses, routes
of administration, and deacetylation degrees would prove vital in un­
derstanding how these polymers can be effectively utilized for animal
production purposes. Therefore, the use of chitosan and chitosan-based
composites presents huge potential for improving animal production
both under health and disease states.
Ethics statement
This study did not involve human or animal subjects. Therefore, no
approvals for human or animal research were necessary.
Funding
This work was supported by the Key Technologies Research and
Development Program of China (2021YFD1300405), Key Technology
Research and Development Program of Shandong province
(2019JZZY020602), the Earmarked Fund for China Agriculture
Research System (CARS-40-K09), and National Natural Science Foun­
dation of China (31772619).
Data availability
No data was used for the research described in the article.
CRediT authorship contribution statement
Victoria Anthony Uyanga: Conceptualization, Visualization, Proj­
ect administration, Writing - original draft, Writing - review & editing.
Onome Ejeromedoghene: Conceptualization, Validation, Resources,
Writing - original draft, Writing - review & editing. Modinat Tolani
Lambo: Investigation, Resources, Writing - original draft, Writing - re­
view & editing. Michael Alowakennu: Investigation, Resources, Visu­
alization, Writing - original draft. Yakubu Adekunle Alli: Investigation,
Resources, Visualization, Writing - original draft. Abigail Adamma Ere-
Richard: Investigation, Resources, Visualization, Writing - original
draft. Liu Min: Resources, Supervision, Formal analysis. Jingpeng
Zhao: Project administration, Supervision, Formal analysis. Xiaojuan
Wang: Resources, Project administration, Formal analysis. Hongchao
Jiao: Resources, Supervision, Formal analysis. Okanlawon M. Onag­
besan: Supervision, Validation, Project administration, Formal analysis.
Hai Lin: Writing – review & editing, Project administration, Supervi­
sion, Funding acquisition.
Declaration of Competing Interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
Data availability
No data was used for the research described in the article.
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