Roger M. Batt, BVSc, PhD, FRCVS, DECVIM
Masterfoods, Mars Inc.
Waltham-on-the-Wolds, Leicestershire, UK
The importance of a normal gastrointestinal microflora in maintaining gastrointestinal and immune function is increasingly recognised. Enteric microorganisms affect structure and function of the intestinal mucosa, the intraluminal metabolism of endogenous bile salts, the metabolism of nutrients and drugs, and furthermore prevent colonisation by pathogenic bacteria. The intestinal microflora normally enjoys a symbiotic relationship with the host, but this can be disrupted when local host defences are reduced and/or by overgrowth of resident microflora or colonisation with enteric pathogens resulting in local and systemic adverse effects. Traditionally, antibiotics were used in managing these patients, but probiotics are emerging as equally and in the long-term more effective tools for re-establishing and maintaining a normal microflora in the gastrointestinal tract.
NORMAL HOST FLORA
The gastrointestinal tract usually contains an enormous number of aerobic and anaerobic bacteria, which form a complex ecosystem. The distribution of bacteria varies within regions of the intestinal tract. In dogs, bacterial numbers are relatively low in the proximal small intestine and gradually increase towards the ileocaecale region with a dramatic increase in the colon, accompanied by a progressive increase in the proportion of gram-negative and obligate anaerobic bacteria. There is considerable variation in the bacterial flora between normal individuals, and concentrations may be affected by a variety of circumstances including environment, diet, scavenging and coprophagia.
Regulation of the gastrointestinal microflora depends upon complex interactions between normal physiological processes and microbial factors. Host factors include gastric acid secretion, intestinal propulsive movements, secretion of pancreatic antibacterial factors, the mucosal barrier, and intestinal immunity. Microbial interactions (e.g., substrate depletion, production of growth inhibitors) also play an important role in favouring growth of a healthy microflora.
EXAMPLES OF CONDITIONS ASSOCIATED WITH AN ABNORMAL FLORA
Small intestinal bacterial overgrowth
Small intestinal bacterial overgrowth (SIBO) describes the proliferation of abnormal numbers of bacteria in the lumen of the small intestine. The definition of what is considered an abnormal flora in the dog is still under discussion. It is classically stated that in normal household pet dogs no more than 105 bacteria per mL of juice should be present in the lumen of the upper small intestine (in contrast to cats which often have much higher numbers including many obligate anaerobes). Recent reviews have questioned the validity of this upper limit of normal, but some of this reported variation reflects inclusion of kenneled dogs, which can be exposed to a greater environmental infection pressure. In dogs with SIBO there are not only increased numbers of intraluminal bacteria, but the composition of the flora also changes to become predominantly Gram-negative and anaerobic, resembling that of the colon. Asymptomatic SIBO has been documented in German shepherd dogs and also laboratory beagles; nevertheless, they can have ultrastructural and biochemical evidence of intestinal damage.
SIBO may develop if there are abnormalities in the physiological processes that regulate the intestinal microflora. Host malnutrition may favour persistence of an abnormal microflora by affecting intestinal mucus secretion and local immunity. The cause of SIBO in dogs is often unknown. However, it appears to be common in dogs with chronic gastrointestinal disease, both as a cause and consequence, and also in exocrine pancreatic insufficiency.
Bacteria (particularly anaerobic species) and their secreted products can directly damage the mucosa or indirectly impair absorption by changing the intraluminal environment, via deconjugation of bile acids, hydroxylation of fatty acids and competition for nutrients. Diarrhoea, steatorrhea and/or weight loss occur because of nutrient malabsorption and secretion of fluid and electrolytes, exacerbated by the osmotic effects of malabsorbed nutrients.
Known bacterial pathogens such as Salmonella spp, Campylobacter spp, Clostridium spp, and enteropathic E. coli may cause gastrointestinal disease by overcoming host defences, including the inhibitory properties of the normal microflora. Bacterially mediated diarrhoea may occur through direct mucosal injury or toxin production. Invading bacteria, such as Salmonella, penetrate the epithelial cells and produce inflammation and necrosis, and haemorrhagic diarrhoea. Enterotoxin producing bacteria can remain on the epithelial surface and promote intestinal fluid secretion without causing obvious morphologic injury. Enteropathic E. coli may also play a role in the aetiopathogenesis of SIBO in some dogs.
Probiotics are defined as live microbial feed supplements that exert beneficial effects on the host by improving its intestinal microbalance. They have a broad spectrum of activity including nutritional, physiological and antimicrobial effects. Benefits are attributed to promotion of an optimum microflora resulting in improvement of digestion, increased resistance to colonisation by enteropathogens, improved gut barrier function, and downregulation of intestinal inflammatory responses. Probiotics may also modulate systemic immunity. The best-studied probiotics are the lactic acid bacteria, particularly Lactobacillus sp. and Bifidobacterium sp
Current data suggest that oral administration of probiotics may be of therapeutic usefulness in a diverse spectrum of gastrointestinal disorders. Their efficacy has been proven in a wide range of gastrointestinal diseases in humans, including infectious bacterial and viral intestinal diseases, inflammatory bowel disease, and several allergic diseases associated with increased gut permeability. Their efficacy in other diseases such as small intestinal bacterial overgrowth and functional gastrointestinal disorders is under investigation.
USE OF PROBIOTICS IN SMALL ANIMALS
Few studies have looked objectively at the benefits of probiotics in companion animals. However, recent reports evaluating a Lactobacillus acidophilus strain in healthy dogs and cats do clearly indicate beneficial effects not only on gastrointestinal but also systemic health. In addition, the same probiotic was effective in reducing faecal shedding of Campylobacter and the rate of re-infection in a large group of cats with campylobacteriosis. Further clinical investigations are needed to assess the efficacy of probiotics in other situations, including diseases such as SIBO which are frequently managed with long-term oral antibiotics.
Probiotics can therefore promote optimal gastrointestinal and systemic health in clinically normal companion animals and can also play a useful role in the management of overt clinical disease.
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