Variations on gut health and energy metabolism in pigs and humans by intake of different dietary fibers

Abstract Many studies have reported that dietary fibers play a crucial role in promoting intestinal health of the host, since it strengthens functions of epithelial barrier and meanwhile maintains intestinal homeostasis of the host by modulating gut microbiota and short‐chain fatty acid (SCFA) production. Pig is a good animal model to study effects of dietary fiber on gut health and microbial community. This review has summarized the relevant knowledge available based on roles of various dietary fibers in gut health and energy metabolism of pigs and humans. Evidences summarized in our review indicated that modulating intestinal microbial composition and SCFA production by consuming specific dietary fibers properly could be conducive to health improvement and disease prevention of the host. However, types of dietary fiber from edible foods exert divergent impacts on gut health, energy metabolism, microbial composition, and SCFA production. Therefore, more attention should be focused on different responses of various dietary fibers intake on host metabolism and health.


| INTRODUC TI ON
Prebiotics are food components that can be selectively fermented, leading to changes in composition and activity of gut microbiota, then contributing to improvement of host health (Gibson et al., 2017). Dietary fibers derived from foods, which include cellulose, hemicelluloses, pectin, gums, mucilage, undigested oligosaccharide, and resistant starch, are usually considered to behave as prebiotics in human health and nutrition (Mudgil & Barak, 2013). Dietary fibers are polysaccharides which linked with more than 10 glycosidic bonds, and they are partially or completely fermented by gut microbiota in the hindgut of pigs and humans to synthesize short-chain fatty acids (SCFA). Dietary fibers could decrease transit time of digesta, increase stool bulk, and reduce blood cholesterol and glucose (Jarrar et al., 2019;Kerckhoffs et al., 2003;Mudgil & Barak, 2013). Apart from those directly physiological responses originated from physiochemical properties of dietary fibers, it could also improve growth and activity of the intestinal microbiota, which underlie some prebiotic effects on host health and disorders prevention (Gensollen et al., 2016). Intestinal microbiota community shaped via microbial fermentation of dietary fiber is beneficial to host health through regulating physiological processes of the intestine and functions of mucosal immunity. More specifically, gut microbiota intensify integrity of the gut barrier comprised by intestinal epithelial cells, suppress colonization of enteric pathogens, and produce antibacterial peptides in the mucus layer of host intestine (Bäumler & Sperandio, 2016;Natividad & Verdu, 2013).
The SCFA produced by microbial fermentation of dietary fibers mainly include acetate, propionate, and butyrate, which play an important role in regulating energy metabolism, immunological function, and gut cell proliferation of the host (Koh et al., 2016). Butyrate is a source of energy for colonocytes to maintain the gut barrier, whereas acetate and propionate are delivered to peripheral circulation through the portal vein to participate in metabolisms of the liver and peripheral tissues Liu, Zhao, et al., 2018).
In addition, several studies have demonstrated that SCFA has diverse metabolic and regulatory activities, such as modulating immune functions, providing energy for cell turnover, and being a histone deacetylase (HDAC) inhibitor (Flint et al., 2012;Thangaraju et al., 2009). Furthermore, there is a broad consensus that SCFA act as physiological signaling molecules to adjust biological processes associated with host health and nutrition. Many researchers reported that SCFA mediates glucose homeostasis by activating G protein-coupled receptors (GPR 41 and 43) and stimulating enteroendocrine L-cells to produce glucagon-like peptide 1 (GLP-1) and peptide YY (PYY), resulting in an increase insulin sensitivity (Mudgil & Barak, 2013;Tolhurst et al., 2012). The SCFA promotes secretion of inflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factorα (TNFα), interleukin-10 (IL-10), and chemokine monocytes chemotactic protein-1 (MCP-1) to enhance intestinal immune barrier function by inhibiting activity of HDAC and stimulating expression of G protein-coupled receptors (Montagne et al., 2003;Smith et al., 2013). Nicolucci et al. (2017) reported that obese patients who consumed inulin reduced plasma triglyceride IL-6 concentrations. Therefore, SCFA plays a crucial role to regulate responses of dietary fiber fermentation by gut microbiota on host metabolisms and health.
As reported by Cappai et al. (2013), a higher starch digestibility from cereals is positively related to a lower amylose to amylopectin ratio in the starch composition under a same starch concentration condition, as starch with high amylose content is less digestible. Therefore, structure and composition of dietary fibers may play an important role in fiber fermentability by gut microbiota. Evidences showed effects of different types of dietary fibers derived from edible foods on gut health and energy metabolism of the host were associated with their physical characteristics and fiber composition (Zhao et al., 2019). Microbial metabolites produced from microbial fermentation of fiber are also varying when pigs and humans consume different types of dietary fiber. A higher proportion of valeric acid accounted for total SCFA was observed when hulled shredded acorns are fed to pigs (Cappai et al., 2020). Illustrating these effects on development of gastrointestinal tract in humans is challenging because of difficulty in sample collection. Alternatively, pig is a good model to study effects of dietary fibers on gut health and microbial composition in humans, considering high similarity of the intestinal biology and gut microbiota community between pigs and humans (Lee et al., 2011). Our hypothesis is that roles of different types of dietary fiber in regulating gut health and host metabolism vary. Therefore, this review summarizes effects of different dietary fibers with varying physicochemical properties derived from commercial diets on energy metabolism, gut morphology, gut barrier function, intestinal microbiota, and SCFA production in both pigs and humans, and practice of dietary intervention using dietary fibers to maintain host health and metabolism. Considering various proportions of dietary fibers derived from different fiber-rich foods and their different physicochemical properties, it is crucial to ingest a variety of fiber-rich foods to benefit animal and human health.

| DEFINITI ON AND CL A SS IFI C ATI ON OF D IE TARY FIB ER S
A widely accepted definition is that dietary fiber is one of the carbohydrates that are indigestible by endogenous enzymes in pigs and humans and meanwhile exert vital impacts on maintaining normal physiological function and energy metabolism of the host (Cummings & Stephen, 2007). Dietary fiber is mainly divided into oligosaccharides and polysaccharides. Oligosaccharides are nondigestible carbohydrates composed of 3-9 monosaccharides which are connected with either α 1-4 or α 1-6 glycosidic bonds, and mainly include fructo-oligosaccharides, galacto-oligosaccharides and isomalto-oligosaccharides, human milk oligosaccharides and xylo-oligosaccharides (Borderías et al., 2005). Edible foods provide many oligosaccharides to pigs and humans, which usually have sweet taste and exhibit prebiotic effects on gut microbiota and host health (Cheng et al., 2017). Polysaccharides are complex carbohydrates, composed of 10 up to several thousand monosaccharides, which are primarily composed of resistant starch, cellulose, hemicellulose, and β-glucan. Cellulose is the most abundant polysaccharides consisting of up to 10,000 glucose monomer units per molecule, and it is the major component of the plant cell wall, which is only partially fermented in the intestine of pigs and humans. Hemicellulose is also a component of the plant cell wall, but it has both linear and branched molecules containing 50~200 pentose units and hexose units, such as β-glucan, glucomannan, arabinoxylan, and xylan (Adebowale et al., 2019). β-glucan is a branched polysaccharide with glucose polymers which lead to its high solubility and fermentability in the intestine (Bashir & Choi, 2017). Resistant starch, which is divided into four types based on its structure and fermentability, is a kind of starch that can pass through small intestine of humans without being fully digested, and reach large intestine to be degraded by beneficial gut bacteria (Sajilata et al., 2006). Pectin, characterized by high viscosity and fermentability, is composed of three different polysaccharides: homogalacturonans, rhamnogalacturonans, and galactomannans (Rejaii & Salehi, 2016). Different kinds of dietary fibers derived from edible foods are showed in Table 1

| PHYS IC AL CHAR AC TERIS TIC S OF D IE TARY FIB ER S
Major physical characteristics of dietary fibers include the following aspects: solubility, water-holding capacity, viscosity, swelling capacity, and bulk density. Based on solubility, dietary fibers in edible foods are divided into two categories: soluble and insoluble chemical components (Ferrario et al., 2017). Water-holding capacity is ability of dietary fibers to combine with water for forming colloidal suspensions, and this ability depends on types of glycosidic bonds and compositions of polysaccharides (Lan et al., 2012). Viscosity is an important physical characteristic that affects physiological function of dietary fibers. Viscosity of pectin and glucan is greater than that of the cellulose and lignin in edible foods for pigs and humans (Dikeman & Fahey, 2006). Moreover, dietary fibers with long chains are easier to form net structures than short-chain fractions, leading to greater viscosity of long-chain dietary fibers. Swelling occurs when structure of dietary fibers solubilizes and is dispersed by incoming water, and therefore, swelling degree is dependent on water-binding capacity of dietary fiber (Knudsen et al., 2013). Expansion and dispersion of dietary fibers allow more rapid access by microbial enzymes, resulting in increased fiber fermentability and SCFA production. Bulk density is defined as the degree of consistency measured by the quantity of mass per unit volume occupied by the fibrous materials (Elleuch et al., 2011). A lower bulk density would lead to more fullness in the gastrointestinal tract, resulting in a reduced appetite and feed intake. In the future, there will be less variation on physical characteristics of different dietary fibers, but the relationship between their physical characteristics and host health and metabolism have been barely studied.

| D IE TARY FIB ER S AND G UT HE ALTH AND ENERGY ME TABOLIS MS OF THE HOS T
Increasingly, researchers have proven that dietary fibers improve gut health of the host ( Figure 1 and

TA B L E 3 The compositions of dietary fibers in common cereal by-products (on dry matter basis)
Item   (Chen et al., 2015). Under the condition of high temperature, pigs and humans can synthesize heat shock protein (HSP) to alleviate heat stress and support stability of the mucosal barrier in the host intestine. A recent study illustrated that chicory fiber intake significantly increased expression of HSP27 in the ileum and colon of pigs, and expression of HSP27 in the ileum was positively correlated with the soluble uronic acid intake (Liu et al., 2012).

| Dietary fibers and intestinal mucosal barrier
Furthermore, many researchers have reported that SCFA production is beneficial to secretion of mucosal proteins in pig intestine, but concentrations and types of SCFA can influence expression of mucosal proteins (Barcelo et al., 2000;Hatayama et al., 2007).  Abbreviations: CRC, colorectal cancer; GLP-1, glucagon-like peptide-1; HSP, heat shock protein; IL-6, interleukin-6. The SCFA produced by microbial fermentation decreases secretion of proinflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factorα (TNFα), and promotes anti-inflammatory cytokine interleukin-10 (IL-10) and chemokine monocytes chemotactic protein-1 (MCP-1), to enhance intestinal immune barrier function (Montagne et al., 2003). The SCFA production was also reported to modulate the immune function of the host by inhibiting the activity of HDAC and stimulating the expression of G protein-coupled receptors (Smith et al., 2013). Sodium butyrate regulates release of interleukin-2 (IL-2), IL-6, interleukin-8 (IL-8), and TNFα by inhibiting HDAC activity and activating the activator protein 1 (AP-1) signaling pathway in intestinal epithelial cells to enhance the intestinal immune function of the host (Cox et al., 2009;Tan et al., 2014). At the same time, sodium butyrate effectively regulates function of T lymphocytes through motivating G protein-coupled receptors (GPR43) to reduce the level of inflammatory factor IL-2 and to increase the secretion of anti-inflammatory factor interleukin-4 (IL-4) and antimicrobial peptide LL-37, which ultimately inhibits the inflammation response of the host (Cleophas et al., 2016;Macpherson et al., 2008).

| Dietary fibers and short-chain fatty acids production
Overall, these results indicate that dietary fiber plays a crucial part in immune function of the host by increasing the SCFA concentration.
Many researchers reported that SCFA mediates glucose homeostasis and fat acids metabolism in the host by activating GPR41, GPR43, and stimulating enteroendocrine L-cells to produce GLP-1 and peptide YY, resulting in improved insulin sensitivity (Mudgil & Barak, 2013;Tolhurst et al., 2012). Pedersen et al. (2013) reported that oligofructose stimulated GLP-1 and insulin secretion to increase host appetite, resulting in depressing intake of food and incidence of obesity. Furthermore, a consumption of barley kernel-based bread to healthy human volunteers, which is rich in β-glucan, improved glucose metabolism and prevented the risk of obese disease (Nilsson et al., 2015). reported that oat β-glucan intake increased the net SCFA absorption in the portal vein of catheterized pigs, but reduced the production of insulin mediated by GLP-1 activity, which is consistent with the previous finding in diabetic patients (Silva et al., 2015). Among the dietary fiber fractions, β-glucan is receiving more attention because it is an easily fermentable energy source for intestinal microbiota. β-glucan is certainly fermented by most of gut microbiota, except for Enterobacteriaceae (Stack et al., 2010).
Intestinal microbiota could produce lactic acid to reduce intestinal pH and further selectively facilitate proliferation of Lactobacillus and Bifidobacterium (Stack et al., 2010). Oat bran, a soluble dietary fiber source rich in β-glycan, produces almost twice the amount of SCFA per gram of dietary fiber compared with wheat bran during microbial fermentation (Zhao et al., 2020). Bach Knudsen and Canibe (2000) detected higher concentration of lactate (11.6 vs. 3.4 mmol/ kg of digested feed) and greater proportion of butyrate accounted for total organic acid (9.1% vs. 6.1%) in the small intestine of pig's model after feeding diets supplemented with oat bran than wheat bran. Zhao et al. (2019) reported that intake of oat bran by pigs had significantly distinct improvement on amounts of lactic acid produced in the foregut, and soybean hulls and sugar beet pulp fed to pigs. They also observed acetate, propionate, and butyrate concentrations in the hindgut in oral bran treatment were higher than corn bran and wheat bran. Freire et al. (2000) investigated the effects of dietary wheat bran, sugar beet pulp, soybean hulls, or alfalfa meal intake on total SCFA production in the cecum of pigs. They found that dietary soybean hulls consumption increased total SCFA concentration by 11.2%, 30.5%, and 27.2% compared with dietary wheat bran, sugar beet pulp, and alfalfa consumption, respectively (Freire et al., 2000).
Overall, variation in fermentability and SCFA production among different types of dietary fibers could be mainly ascribed to the differences in their chemical compositions and physicochemical properties. There is great potential to improve gut health and immune function of humans by regulating the intake of different kinds of dietary fibers to manipulate the production of SCFA.
The present argument is that SCFA produced in the intestine not only derived from microbial fermentation of dietary fibers, but also resulted from the secretion of the nondietary fiber components  (Ingerslev et al., 2014;Nielsen et al., 2015). Therefore, it would be extremely difficult to measure actual produced SCFA in vivo, as produced SCFA are rapidly metabolized by gut microbiota or absorbed by the host. The absorption and net production of SCFA, rather than a real-time concentration of SCFA in the gut, derived from gut microbiota to ferment different types of dietary fibers should be quantified to understand the fermentable capacity of dietary fibers and the metabolic pathway of SCFA in the gut of the host.

| Dietary fibers and gut microbiota
Microbial community in the host intestine is a complex and dynamic ecosystem that produces crucial metabolites to regulate host metabolism, such as SCFA, 5-hydroxytryptamine, polymyxin, and bacitracin. Microbial metabolites depress proliferation of harmful bacteria and balance interactive competition between "beneficial bacteria" and "harmful bacteria." In addition, microbial metabolites play important roles in maintaining intestinal barrier, facilitating immunological function, and modulating gene expression of host metabolism (Cani, 2016;Guo et al., 2008). An increment of microbial activity was found in the intestine of pigs fed diets containing a high content of dietary fiber, as indicated by increased bacterial counts and ATP concentration Liu, Zhao, et al., 2018). It indicates that dietary fibers can activate microbial activity, resulting in producing more microbial metabolites. Many reports have indicated that Firmicutes and Bacteroidetes are the two dominant phyla in the gastrointestinal tract of pigs and humans, which account for about 90% of the gut microbiota (Bian et al., 2016;Liu, Zhao, et al., 2018). Firmicutes utilize dietary fibers to produce SCFA, especially butyrate. Bacteroidetes have a great capacity for degradation of dietary fibers to produce propionate, such as Prevotella (Flint et al., 2008). Mu et al. (2017) reported that dietary supplementation with alfalfa meal increased populations of Firmicutes and Bacteroidetes compared to wheat bran in neonatal piglets. Similarly, diets rich in resistant starch increased relative populations of some specific members of Firmicutes, as well as a ratio of Firmicutes to Bacteroidetes in human's intestine (Maier et al., 2017). In contrast, Ferrario et al. (2017)  Small intestine is mainly responsible for food digestion and absorption, while large intestine is important for microbial fermentation of substances (Healey et al., 2020). Hindgut of pigs and humans contain a larger proportion of Firmicutes than small intestine, indicating that large intestine might undertake a crucial role in microbial fermentation of dietary fiber (Flint et al., 2008). Escherichia-Shigella, Lactobacillus, Streptococcus, and Enterococcus, dominant genera of intestinal microbiota in ileal digesta, are the major bacterial species with greater abundances compared with large intestine of the pig (Zhao et al., 2019). Greater populations of Escherichia-Shigella and Streptococcus are always considered as pathogenic bacteria related to host infection and enteric diseases, such as diarrhea symptoms. Thus, occurrences of enteropathies are primarily associated with microbial composition in the upper gut (Healey et al., 2020).
Lactobacillus is a beneficial bacterial specie to improve gut health of the host, so that it is extremely crucial to maintain balance of different bacteria in the gut by dietary nutrients intervention. An altered gut microbiota composition derived from lack of low dietary fibers could lead to a severe deterioration of mucus layer and increased susceptibility to infections and chronic inflammatory diseases (Desai et al., 2016;Makki et al., 2018). Therefore, dietary fiber ingested from foods has a potential to prevent against metabolic diseases in humans by reshaping composition of gut microbiota. However, ef-

| SUMMARY AND PER S PEC TIVE
There are many complicated and subtle interactions between types of dietary fiber and gut microbiota, SCFA production, and host health. It has been widely accepted that SCFA, especially butyrate,

ACK N OWLED G M ENTS
The authors are grateful to the professional suggestions from Dr.
Zhaokai Yang (College of Science, China Agricultural University) for carbohydrate structure and to the Postdoctoral Innovative Talent Support Program (No. BX20200365).

CO N FLI C T O F I NTE R E S T
None of the authors had a financial or personal conflict of interest in relation to the present study.

E TH I C A L A PPROVA L A N D CO N S E NT TO PA RTI CI PATE
Not applicable.

DATA AVA I L A B I L I T Y S TAT E M E N T
All authors consent that raw data presented in this review are available after publication. Please contact author for data requests.