The ‘gut health’ response to dietary Bio-Mos®: effects on gut microbiology, intestinal morphology and immune response

Published on: 5/16/2007
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Health and development of livestock, companion animals and humans depend greatly on a stable and healthy gastrointestinal microbial population. Rapid changes in the microflora and/or the proliferation of intestinal pathogens can lead to gastrointestinal diseases or even death. The gut microflora depend on the nutrient availability in both the small and large intestine.

Processing techniques that overheat feed or poor diet formulation can reduce enzymatic digestion in the intestine, leading to increased flow of substrate available for microbial fermentation in the large intestine. This may lead to bacterial overgrowth leading to digestive problems such as gastroenteritis or bloat.

Bio-Mos®, a mannan-based oligosaccharide derived from the cell wall of Saccharomyces cerevisiae, is used as a pro-nutrient feed ingredient to promote gut health and thereby performance in food animals. Recent reports have highlighted the Bio-Mos® benefits in food animals in terms of disease resistance and performance (Hooge, 2004a,b; Kocher et al., 2004; Miguel et al., 2004). While comparatively few studies have been conducted with Bio-Mos® in dogs, results to date suggest similar patterns of response. The following paper reviews research on the influence of Bio-Mos® on gut microbial populations, intestinal morphology and immune function.


Effects on gut microbial populations

STIMULATION OF BENEFICIAL BACTERIA, REDUCING PATHOGEN COLONISATION

Bifidobacteria and Lactobacillus spp. are considered ‘beneficial’ microbial populations. Studies in humans have shown that both Bifidobacteria and Lactobacilli spp. competitively exclude pathogens such as Salmonella, E. coli or Campylobacter (Gibson and Wang, 1994). Lactic and other acids produced by beneficial species decrease intestinal pH and create an unfavourable environment for pathogens. In comparison to humans and farm animals, the most significant difference in the microflora of dogs is the much lower concentration of Bifidobacteria in the canine intestine (Benno et al., 1992).

The use of specific carbohydrates to selectively stimulate the growth of Bifidobacteria in the intestine of dogs has been the subject of several studies (Flickinger et al., 2003; Swanson et al., 2002a; Zentek et al., 2003).

Addition of fructo-oligosaccharide (FOS) has been shown to selectively stimulate the population of Bifidobacteria and reduce the risk of gastroenteritis.

Zentek et al. (2003) and Russell (1998) (in Swanson and Fahey, 2002) both demonstrated that dogs fed chicory (a natural source of FOS) had significantly higher Bifidobacteria populations compared to dogs fed control diets. The inclusion of chicory also significantly decreased the concentration of C. perfringens. FOS interacts with the gastrointestinal microflora by increasing the number of FOS-fermenting, beneficial bacteria, which in turn exclude pathogens through competition for nutrients, changes in the intestinal environment such as reduced pH or the presence of bacterocins.

Studies in food animals have shown that dietary inclusion of another type of oligosaccharide, mannan oligosaccharide (Bio-Mos®, Alltech Inc.), derived from the outer cell wall of a specific strain of Saccharomyces cerevisiae, has been associated with reductions in Salmonella and E. coli (Spring et al., 2000). In contrast to FOS, mannan-based oligosaccharides can have a direct impact on pathogenic enteric bacteria colonization.

Mannose residues essentially block the type-1 fimbriae by which many bacteria including many pathogenic coliforms attach to the intestinal wall (Spring et al., 2000). Attachment is key to the successful colonisation of the gut, culminating in the release of toxic metabolites that characterise disease symptoms.

Swanson et al. (2002b) examined gut microbial responses of dogs fed either 1 g of fructo-oligosaccharide (FOS), 1 g of Bio-Mos®, or 1 g each of FOS and Bio- Mos® in combination per day for 14 days. Dogs given Bio-Mos® had lower total faecal aerobic bacteria and tended to have greater faecal concentrations of lactobacilli (Table 1). In a subsequent study, dogs supplemented with 4 g FOS + 2 g Bio-Mos®/day exhibited increased faecal bifidobacteria and faecal and ileal lactobacilli concentrations (Swanson et al., 2002c).

Although oligosaccharides may maintain gut microbial ecology of healthy adult dogs, use of prebiotics may be most beneficial in populations that have abnormal gut ecology or compromised immune systems (e.g., geriatric dogs, young weanling puppies, or dogs under stress). It is known that in dogs the number of pathogens such as C. perfringens increases with age, and at the same time the number of beneficial bacteria (Bifidobacteria ssp.) decreases (Benno et al., 1992; cited by Grieshop et al., 2004). Grieshop et al. (2004) reported that the addition of 1% Bio-Mos® to diets fed geriatric dogs (pointers and beagles 8-11 years) had a beneficial impact on the gut microflora as evidenced by increased concentrations of bifidobacteria (P<0.05) (Table 2). Faecal E. coli concentrations were reduced (P<0.05).

While changes in populations of C. perfringens were not noted in the studies conducted by Swanson et al. (2002) or Grieshop et al. (2004), other studies in both dogs and food animals have observed reductions in numbers of this species in response to Bio-Mos® (Sims et al., 2004; Choct et al., 2005). Strickling et al. (2000) found that faecal C. perfringens concentrations tended to be lower in dogs given Bio-Mos®, however faecal bifidobacteria concentrations were unaffected by FOS, Bio-Mos® or a xylo-oligosaccharide in this study (Table 3). Ileal microbial populations were unaffected.

Changes in C. perfringens populations suggest a mode of action for Bio-Mos® other than one mediated by mannose recognition. Unlike the majority of E. coli and Salmonella spp., Clostridia do not attach to the intestine via type-1 fimbriae. Experiments with pigs, poultry and calves have demonstrated effects in animals given Bio-Mos® on intestinal morphology as well as both innate and acquired immune system components that may aid in explaining observed reductions in C. perfringens. These responses, which include changes in crypt depth, mucin production and changes in secretory and/or circulatory antibodies are discussed below.


Table 1. Effect of FOS, Bio-Mos® and their combination on faecal microbial populations of dogs1.
1Adapted from Swanson et al. (2002).



Table 2. Effect of oligosaccharides supplements on faecal microbial concentrations (least squares means, log10 CFU/g dry faeces) of senior dogs1.
1Adapted from Grieshop et al., 2004
2NS=not significantly different (P>0.15).



Table 3. Evaluation of FOS, xylooligosaccharide (XOS) and Bio-Mos® on ileal and faecal microbial concentrations (log CFU/g DM)1.
1Adapted from Strickling et al., 2000
1Probability of greater F-value.
cStandard error of the mean, n = 6.


Modulation of immune responses

Interest exists at all levels in finding ways to enhance immunocompetence, however dietary influences on immune status have been a central focus in recent years.

The requirements for nutrients, including the essential trace elements and several vitamins, are acknowledged to be higher for optimum immune fuction and the ability of functional foods to modulate immune responses is also recognised. Ingredients like Bio-Mos®, which promote efficient responses of the innate and acquired immune system, are finding roles in diets for animals where immunity is easily compromised such as those fed young and geriatric animals, and in gestating/lactating animals to promote optimum health of neonates.


NEONATAL HEALTH: ROLE OF BIO-MOS® IN GESTATION DIETS

Colostrum quality, as defined by immunoglobulin (Ig) content, has been shown to be enhanced when Bio-Mos®
is included in gestation diets of mares, sows and cows.

O’Quinn et al. (2001) found concentrations of IgA, IgG and IgM in colostrum were all increased by the addition of Bio-Mos® to the sow diets beginning 14 days pre-farrowing. Similar responses were noted by Newman and Newman (2001). In both cases associated increases in weaning weight were noted. Ott (2002) found that foals nursing mares given Bio-Mos® prepartum had higher serum IgM values (P= 0.04) and consistently higher IgG values throughout the 56-day study. This was associated with reduced diarrhoea incidence. In a subsequent study mares fed Bio-Mos® had higher colostrum IgG (P=0.05), IgA (P=0.05), and tended to have higher colostrum IgM (P=0.06) (Spearman and Ott, 2004). Specific immunity was enhanced by Bio-Mos® supplementation of dry cow diets as evidenced by greater serum rotavirus neutralization titers at calving (Franklin et al., 2005).


INNATE, HUMORAL AND CELL-MEDIATED IMMUNE RESPONSES TO BIO-MOS®


Dietary factors that enhance ability to mount a swift and effective immune response to pathogen challenge are of interest for all species. A wide range of techniques have been employed to investigate effects of Bio-Mos® on immune function. Responses in innate and cellmediated immunity include increased activity/ effectiveness of phagocytic cells (Sisak, 1995; Zennoh, 1995), reduced incidence of vaccine failure in broilers (Kõrösi and Kõrösi-Molnár, 2003), reduced inflammatory (fever) response in poults injected with LPS from S. typhimurium strain SL 684 (Ferket, 2002), and changes in lymphocyte proliferative response to mitogens (PHA) in broilers (Cotter and Weinner, 1997).

Humoral immune modulation in Bio-Mos®- supplemented animals has also been noted. Responses include increased plasma IgG and bile IgA in turkeys (Savage et al., 1996); higher maternal antibody titres in progeny of broiler breeders fed Bio-Mos®- supplemented diets (Shashidhara and Devegowda, 2003) and elevated titres to SRBC and BSA in commercial layers (Cotter et al., 2000).

Increases in ileal IgA, along with a higher percentage of serum lymphocytes, were also noted in dogs given 2 g FOS + 2 g Bio-Mos®/day (Swanson et al., 2002c).

This improvement in local immunity is of particular interest with regard to intestinal pathogens. Produced in large quantities by the mucosal immune system, IgA is the only antibody secreted into the intestinal lumen.

By promoting secretion of IgA into the gut mucosa layer, pathogenic agents become more labile to the phagocytic action of gut-associated lymphocytes (Ferket, 2004).

In studies with food animals, the indirect (and welcome) responses to enhanced immunity are improved weight gain and efficiency, which are assumed to reflect a reduced need to divert nutrients to immune function. Importantly, this implies an overall lower, not ‘stimulated’ immune response.


CHANGES IN INTESTINAL MORPHOLOGY IN RESPONSE TO BIO-MOS®

Bio-Mos® supplementation also affects intestinal morphology, which has an important role in enteric disease resistance. Ferket (2002) examined jejunum villi morphology in 14-day old poults given diets supplemented with no additive, Bio-Mos® or virginiamycin. Bio-Mos® had the greater effect on gut morphology. Villus height was unaffected, however a decrease in crypt depth approached significance and villus height:crypt depth ratio was significantly greater than the control or virginiamycin treatments.

The muscularis layer was also thinner in turkeys receiving Bio-Mos® and there were increased numbers of goblet cells per mm of villus height compared with control birds. Iji et al. (2001) also observed an increase in jejunal villus height:crypt depth ratio in broilers given Bio- Mos®, but this was due to a significant increase in villus height rather than crypt depth. These researchers also observed that Bio-Mos® significantly increased protein:DNA of jejunal mucosa and increased the brush border enzymes maltase, leucine aminopepidase and alkaline phosphatase.

Increases in goblet cell density similar to that noted above have also been reported in response to Bio-Mos® in other studies. The significance of higher goblet cell density in terms of defence against intestinal pathogens is that the mucus layer coating the surface of the intestinal epithelium is the first major barrier to enteric infection. Savage et al. (1997) found that goblet cell numbers were increased in the duodenal loop and in the area of Meckel’s diverticulum of 8-wk old poults, which was associated with reduced crypt depth (P<0.05).

Weight gain and efficiency of Bio-Mos®-supplemented poults was also significantly improved, which may have been due at least in part to more surface area available for nutrient absorption.

Higher goblet cell density was also noted in the villi of dogs given Bio-Mos®-supplemented diets that included either beet pulp or soy hulls as soluble fibre sources (Kappel et al., 2004). Bio-Mos® also increased soluble fibre digestion, however total and insoluble fiber digestibilities were unaffected (Table 4).

Table 4. Effect of feeding Bio-Mos® on soluble fibre digestibility and acetate production in the canine digestive tract.
abMeans differ, P<0.05
Kappel et al., 2004



Conclusions

Gut health involves maintenance of a robust gut microbial population and a chemical environment conducive to enzymatic digestion along with the normal morphology of the intestinal epithelium. Unlike intensively-reared food animals, pets are less likely to exist in the presence of continuing exposure to enteric pathogens. It remains desirable, however, to formulate pet foods in consideration of the effect gut microbial ecology has on food digestion and ‘whole animal’ health.

When a balanced and adequately high population of bacteria is in place, intestinal pH is maintained in the range optimum for digestive enzyme activity, which prevents shifting the site of digestion to the hindgut, and opportunistic pathogens are rapidly excluded.

Bio-Mos®, a yeast cell wall-derived mannan oligosaccharide, is known to affect microbial populations with a resulting increase in desirable versus undesirable species. Gut morphology is positively affected with an increase in surface area for absorption. Lastly, modulation of innate, cell-mediated and humoral immune functions have been noted in all species examined. This functional food has application in a wide variety of pet foods, but may be most beneficial in diets where animals are prone to dysbiosis including young animals, geriatric pets, and those subjected to the stress of travel and/ or competition.


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Authors: ANDREAS KOCHER AND LUCY TUCKER
Alltech Biotechnology Centre, Dunboyne, Co. Meath, Ireland
 
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