What Is the Use of ISO Malto Oligosaccharide?

Isomalto-oligosaccharides, also known as α-oligoglucose, are a type of oligosaccharide abbreviated IMO (Isomalto-oligosaccharide). IMO is a straight-chain maltose molecule with branched chain-linked disaccharides and oligosaccharides. IMO is also known as branching oligosaccharides and α-glucosides. The molecules contain α-1,4 bonds, α-1,6 bonds, a small amount of α-1,3 bonds and α-1,2 bonds. The main components are isomaltose, panose and isomaltotriose, followed by isomaltotetraose, melezitose and melezitose.

Isomaltulose oligosaccharides are widely found in plant-based feeds such as barley, wheat, and potatoes, and rarely exist in a free state in nature. Yang Shuming (1999) reported that oligosaccharides are produced from starch by the action of β-amylase and α-glucosidase; they can also be produced by inverting maltose to α-glucose or by the reverse synthesis of glucose. The finished product contains 50%-70% oligosaccharides, which can basically resist degradation by gastric acid and digestive enzymes after entering the digestive tract, and pass through the stomach and small intestine smoothly to reach the posterior part of the digestive tract.

1 Research overview of oligosaccharide isomaltose

The enzymes secreted by animals can only hydrolyze α-1,4 glycosidic bonds. IMO contains other types of glycosidic bonds, which are difficult to be utilized in the early part of the digestive tract. Several indigestible carbohydrates are considered to have the potential to function as chemical prebiotics. The beneficial effects of these non-digestible components of feed are now largely established.

1.1 Nutritional effects 

Bailey et al. (1991) showed that oligosaccharides such as IMO cannot be degraded in the upper digestive tract and can reach the lower intestine directly. These substances cannot be detected in the feces, indicating the fermentation of oligosaccharides by colonic microorganisms. Fukuyasu et al. (1987), Mathew et al. (1993), and Howard (1995) showed in pig experiments that IMO promotes bifidobacteria and lactobacilli in the intestine and inhibits Escherichia coli. Zhang Hongfu et al. (2001) showed that the addition of IMO significantly reduced Escherichia coli (P<0.05) and significantly increased Lactobacillus and Bifidobacterium (P<0.05) in the intestinal flora of early weaned piglets. The addition of oligosaccharides to the feed has a significant regulatory effect on the microbial flora of the digestive tract. However, the results of the experiment by Gabert et al. (1994) were not affected, which may be related to the variety of oligosaccharides.

1.2 Role in animal nutrition and immunity

The role of IMO in nutritional immunity is to stimulate the proliferation of beneficial bacteria and nutrient absorption, exerting an indirect immune effect; inhibit the reproduction and colonization of pathogenic bacteria, enhance immunity against infection; reduce the effect of factors such as phytohaemagglutinin that are harmful to the internal environment; and possibly directly stimulate or protect immune factors.

Oligosaccharides promote the proliferation of beneficial bacteria such as lactobacilli and inhibit pathogenic microorganisms in various ways. One of these is the barrier effect, which is described as competitive inhibition of the intestinal mucosal epithelium. The second is the inhibitory effect of metabolites on pathogenic bacteria. Stewart et al. (1993) and Tomilka et al. (1992) have confirmed that IMO can promote the proliferation of bifidobacteria and lactobacilli, which produce low-energy fatty acids during metabolism, thereby lowering the pH value. Escherichia coli and Salmonella are sensitive to acidic conditions, and their growth is inhibited by low pH values. The agglutinating activity of the lactic acid bacteria and bifidobacteria in the intestine is significantly higher than that of pathogenic bacteria such as Escherichia coli and Salmonella. This may be one of the reasons why the normal intestinal flora has a significant competitive advantage in competitive exclusion.

1.3 Regulating the immune system of animals

It has been reported that the immunomodulatory effect of oligosaccharides as an immune adjuvant can enhance cellular and humoral immunity, and that it has a promoting effect on the proliferation of beneficial bacteria, thereby regulating the immune system (Gibson & Roberfroid, 1994). The adjuvant effect of oligosaccharides can enhance cellular and humoral immune functions (Yang Shuming, 1999). Zhang Hongfu et al. (2000) showed the effect of IMO on immune levels. Lessard et al. (1987) fed weaned piglets with lactic acid bacteria fermentation products, and the IgG level in piglet serum increased significantly. Oligosaccharides promote the rapid excretion of Salmonella from the intestine and inhibit its transfer to the organs (Wu Lianfu, 1998). Morales et al. (1995) believe that oligosaccharides, as a type of soluble fiber, may reduce the colonization of harmful bacteria and the migration of colonization sites, and help systemic immunity.

1.4 Oligosaccharides and prebiotics

The effect of prebiotics in practical use varies greatly, because prebiotics are mainly live bacterial preparations, and they are difficult to colonize in a short time under the dominance of the indigenous flora of the digestive tract. Oligosaccharides exert their prebiotic effect by regulating the intestinal flora, and they also have direct physiological and physical functions.

They are highly compatible with live bacterial preparations and antibiotics, and are conducive to large-scale popular application. Both live bacterial preparations and oligosaccharides have the effect of regulating the flora in the digestive tract of animals (Xu Xurong et al., 1999; Huo Guicheng et al., 1994). Oligosaccharides can be combined with prebiotics. Watanabe Naohisa and others in Japan studied the effect of isomaltose and microorganisms, and evaluated the feeding effect on 25-day-old piglets. 5 weeks after adding isomaltose, the weight gain increased by 45%, and IMO combined with a type of microbial bacteria increased weight gain by 8% (Zhongkai Zhou, 1999).

Under certain conditions, oligosaccharides can also replace the effects of antibiotics. Feeding piglets with a syrup containing 30% oligofructose from Jerusalem artichoke (Jerusalem artichoke) resulted in a 6% increase in body weight compared to piglets supplemented with antibiotics (50 mg/kg zinc bacitracin)  (Zerhonig, 1999). It can also reduce the amount of antibiotics used in piglets (Jinfengqiu, 1999). Shi Baoming and Shan Anshan (1999) concluded that the effect of oligosaccharides on piglets is not consistent.

2 Application of IMO in production

2.1 Effect of IMO on weight gain and feed utilization

Some oligosaccharides have many similarities with non-starch polysaccharides (NSP), which are abundant in plants and microorganisms (Mul and Perry, 2001). In vitro tests have shown that IMO is only utilized by some beneficial bacteria containing specific glycosidic bonds, thus promoting the growth of bifidobacteria and lactobacilli. In addition, IMO can also bind to the exogenous lectin, to prevent the attachment of pathogens to the intestinal wall, thereby cutting off the infection route of attachment-reproduction-pathogenesis, and carrying the pathogenic bacteria out of the body to maintain animal health.

Most feeding trials have shown that the addition of oligosaccharides does not significantly increase animal daily weight gain and feed utilization. Boldon (1993) tested on piglets and found that adding 1-2 g/kg galactose oligosaccharides increased piglet weight gain by 6.8% and decreased the feed conversion ratio by 1 % ~2%; Boldon (1993) also reported that the addition of α-glucan oligosaccharides increased the daily weight gain of 35-day-old weaned piglets (4 weeks of rearing period) by 3%-4%, and the feed conversion efficiency increased by 3% ~4%;    Mathew (1997) added 0.5% galacto-oligosaccharides to the diet of 21-day-old weaned piglets. After a 9-week feeding trial, the feed intake was significantly different from that of the control group (P<0.05), while there was no difference in average daily gain and feed efficiency.

This may be due to the following reasons: Firstly, before IMO reaches the hindgut, some of it is broken down and lost under the combined action of intestinal microorganisms and animal digestive enzymes, and consequently loses its expected stimulating effect on the hindgut microorganisms. In fact, IMO is already partially degraded by microbial enzymes when it reaches the end of the ileum (Oku, Tokunaga, 1984; Tsuji et al. 1986; Fischbein, Kaplan & Gougph, 1988) Although most of the IMO components reach the hindgut after fermentation by Escherichia coli, the effect on beneficial microorganisms is also limited by the dosage. Second, the feed sources and endogenous complex polysaccharides or mucopolysaccharides in the intestine can also be metabolized to produce oligosaccharides, which affect intestinal function and microbial dynamics and affect the ability of the added IMO to work. However, Liu Xuelan, Xie Youmei et al. (2002) reported that adding 0.4% IMO to the diet of weaned piglets improved the pig's immune and digestive absorption functions, increased feed intake, reduced the diarrhea index, promoted growth, and reduced the feed to weight ratio.

2.2 Effect of IMO on diarrhea rate

The proliferation of beneficial bacteria in the digestive tract and the reduction of harmful bacteria will reduce the incidence of E. coli diarrhea. On the one hand, oligosaccharides can promote the proliferation of beneficial bacteria, inhibit or repel the proliferation of some conditional pathogenic bacteria, inhibit the adhesion of conditional pathogenic bacteria to intestinal mucosal cells, adsorb toxins, and increase the animal's non-specific immune function, thereby reducing the chance of bacterial and viral diarrhea. Bolduan (1997) used 0.2% biological mannan oligosaccharides added to 35-day-old weaned piglets to reduce the incidence of diarrhea. On the other hand, oligosaccharides have strong water absorption, and excessive use can cause physical diarrhea and increase the incidence of diarrhea.

MulAJ&Perry FG (1993) reported that the addition of oligosaccharides above 0.5% of the intake will increase the rate of chyme flow and increase the incidence of soft stools. Therefore, most of the recommended dosage of oligosaccharides is below 1.0%.

2.3 Effect of IMO on the weight and size of animal organs

Zhang Hongfu et al. (2000) reported that IMO had little effect on the relative liver weight and spleen weight of animals, but it could slightly reduce the relative weight and relative length of the small intestine, which may be due to IMO's selective probiotic effect. IMO could slightly increase the relative weight of the cecum and large intestine, but the relative length of the cecum and large intestine basically remained unchanged. This may be because the residual IMO in the cecum can increase the surface area and weight of the intestinal mucosa by enhancing the water retention of the chyme and expanding the volume.

2.4 Effect of IMO on the content of Lactobacillus acidophilus and Escherichia coli in the chyme

Oligosaccharides can be selectively utilized or promote the proliferation of most lactobacilli, bacilli, and gram-positive bacteria such as Streptococcus faecium, but cannot be utilized by gram-negative bacteria such as Escherichia coli and Salmonella. Some people call oligosaccharides with this property oligosaccharides. Hillman et al. (1999) pointed out that the ratio of lactobacilli/enterobacteria in feces can be used to assess the resistance of pigs and chickens to pathogenic bacteria, because lactobacilli inhibit the growth of enterotoxigenic E. coli and adhesion to the intestinal mucosa, and are resistant to Salmonella.

A large number of studies have shown that after weaning, the intestinal flora of piglets changes, with a general trend of an increase in the concentration of pathogenic bacteria such as E. coli and a significant decrease in beneficial bacteria such as lactobacilli (Mathew, 1997; Mathew, 1993). This shows that after weaning, due to factors such as changes in the feed and a decrease in the level of autoimmunity, the inherent microbial flora of the piglet begins to decline.

An increase in the concentration of E. coli in the intestine after weaning is considered to be one of the main causes of one of the main causes of diarrhea in piglets (Kenworthy and Grabb, 1963; Svendson and Larsen, 1977; Hampson et al., 1985). Fukuyasn (1987), Farnworth (1992), and other studies on animals such as piglets, mice, and chickens, as well as humans, have shown that oligosaccharides have the effect of regulating the microbial flora in the digestive tract.

Wang Ran, Shao Chunrong et al. (2002) added 1% IMO to the basal diet of day-old chicks, and the number of Escherichia coli in the jejunum and cecum was significantly lower than that in the control group (P<0.05), and the number of Lactobacillus was significantly higher than that in the control group (P<0.05). Zhang Hongfu Zhang et al. (2001) added 0.5% IMO to the basal diet of early weaned piglets, and the cecal and colonic E. coli concentrations were significantly lower than those of the control group (P<0.05), while the lactobacillus concentration was significantly higher than that of the control group (P<0.05). The results of the above authors' research show that different oligosaccharides have a regulatory effect on the microorganisms in the digestive tract of animals.

2.5 Effect of IMO on the relative levels of serum IgG, IgA and the ratio of T-lymphocytes to B-lymphocytes

Most experiments have shown that IMO has no significant effect on IgG and IgA. Some scholars believe that IMO can enhance the efficacy of drugs and antibody immune responses, thereby increasing the humoral and cellular immune responses of animals and promoting an increase in the number of lymphocytes in the blood. The addition of IMO at production doses to feed cannot significantly affect the composition of T-lymphocytes and B-lymphocytes. This may be due to the fact that when pathogenic molecules enter the bloodstream, T-helper lymphocytes can recognize the pathogens, stimulate a series of immune pathways, cause proliferation and activation of lymphocytes, and the molecular weight of IMO is far from the unobstructed molecular weight range of antigen molecules, it cannot directly stimulate T-lymphocyte response through a direct pathway. Due to the lack of strongly charged sites, its role as an antigen-helper factor is also limited.

2.6 Observation of the effects of IMO on intestinal mucosal morphology

After weaning, the intestinal mucosa of piglets atrophies, the intestinal mucosal epithelium villi become shorter, and the crypts become deeper (Hampson, 1986; Yan Runan, 1993; Gu Xianhong et al., 1999). Existing data show that the intestinal microflora directly or indirectly affects the dynamic changes of crypt cells and mucosal epithelium (Deplancke & Gaskins, 2001). In the diet of chicks, the addition of 0.5% IMO significantly increased the height of the villi of the mucosal epithelium of the cecum (P<0.05), and the weight of the cecum also increased (P<0.05).

3 Regarding the amount of IMO added

it is generally considered that the addition of 0.5% IMO to the diet of weaned piglets and broiler chickens is more effective.

4 Conclusion

IMO, as a relatively affordable feed additive, has good prospects for use in animal husbandry and the feed industry. A deeper understanding of its physicochemical properties, an understanding of its mechanism of action and stability during production, and an exploration of its use and dosage are of great significance for our full application of this new additive, reducing the diarrhea rate, and thereby improving animal productivity. At this stage, the following issues need attention: (1) Establish a basic quality and technical control index to monitor the quality of IMO products to avoid production losses due to unstable quality. (2) In view of the inconsistent test results, more scientifically designed scientific experiments are needed to prove the application effect, so that its application can be further expanded in depth and breadth and the utilization value of resources can be improved. It has also been reported that IMO can replace some of the antibiotic dosage in animal diets, which requires further research in production.