11 Apr 2016
Marge Chandler considers the benefits of using “good bacteria” and analyses research exploring their potential use.
Marge Chandler
Job Title
Figure 1. Inflammatory bowel disease in a dog resulting in inflamed intestinal mucosa.
Probiotics have the potential to support beneficial changes in microbiota and impact disease.
Human studies have looked at the positive effects of probiotics on glucose tolerance, weight control, atopic dermatitis, liver disease, inflammatory bowel disease (IBD), respiratory disease, dental caries and gingivitis.
Probiotics have been defined variously by different organisations, but are generally described as “live microorganisms, which, when consumed in adequate amounts, confer a health effect on the host” or similar (Guarner and Schaafsma, 1998).
Probiotics have been used safely in foods for many years, but few safety studies exist. Four potential side effects theoretically exist (Doron and Syndman, 2015):
Minor gastrointestinal (GI) upset has also been reported occasionally in humans and cats (Doron and Syndman, 2015; Waugh et al, 2013).
Lactobacillus bacteraemia and invasive infection with Saccharomyces cerevisiae have been reported in immunosuppressed humans, especially those with IV catheters or in intensive care (Salminen et al, 2004; Enache-Angoulvant and Hennequin, 2005). The most commonly reported infections were fungaemia with S cerevisiae or Saccharomyces boulardii (Doron and Syndman, 2015).
No probiotic-induced septicaemia episodes have been reported in dogs or cats. Two in vitro studies have shown increased adhesion of Campylobacter jejuni to canine intestinal mucosa with Enterococcus faecium (Rinkinen et al, 2003; Vahjen and Männer, 2003). E faecium may, therefore, favour the adhesion and colonisation of C jejuni in the dog’s intestine, making it a potential carrier and source for infection. It should be noted this E faecium strain is different from the strain available commercially and no evidence exists of Campylobacter-associated diarrhoea associated with E faecium administration.
A clinical trial of a multistrain probiotic in humans with severe pancreatitis showed a higher mortality rate in those treated, due to bowel ischaemia (Besselink et al, 2008). The probiotics may have increased the gut mucosa oxygen demand or triggered a gut inflammatory reaction. Other studies have shown decreased septic complications in human pancreatitis patients given a probiotic (Doron and Syndman, 2015).
No reports exist of deleterious effects of probiotics in canine or feline pancreatitis, but acute severe pancreatitis is probably a contraindication.
Lactic acid bacteria possess plasmids that can cause resistance to several antibiotics. While, theoretically, this could cause antibiotic resistance, it has not been proven to occur in humans or animals.
Four bacterial probiotic strains have been examined by the European Food Safety Authority for safety and efficacy in dogs, including two E faecium strains (NCIMB 10415 and E1705), Lactobacillus acidophilus DSM 13241 25 and Bifidobacterium animalis (Schmitz and Suchodolski, 2016). The combination probiotic VSL#3 showed no safety concerns other than a few vomiting episodes and changes in stool quality and appetite (Waugh et al, 2013), and B animalis strain AHC7 fed to growing beagles was well tolerated with no safety concerns (Kelley et al, 2010).
The joint food and agriculture organisation of the United Nations/World Health Organization expert consultation on evaluation of health and nutritional properties of probiotics developed guidelines for evaluating probiotics in human food (FAO, 2006). It also suggested a safety assessment should determine the patterns of antimicrobial drug resistance, metabolic activities, side effects during trials, toxin production, haemolytic potential and lack of infectivity.
Trials using probiotics should include surveillance for infections and other adverse effects. Patients liable to be at increased risk for adverse effects include those with compromised immune systems, central venous catheters and possibly those with cardiac valve disease (Doron and Syndman, 2015).
Several studies have shown some benefit in the use of probiotics in acute GI disease. Giving VSL#3 to puppies with parvoviral enteritis increased the percentage of survival (90% in treated versus 70% in untreated; Arslan et al, 2012).
In shelter cats and dogs, E faecium SF 68 resulted in significantly lower incidence of diarrhoea in cats, although the results in dogs did not reach statistical significance (Bybee et al, 2011). In dogs with acute gastroenteritis, a probiotic cocktail shortened production of a normal stool from 2.2 days to 1.3 days (Herstad, 2010).
Using canine-derived B animalis AHC7 in dogs with acute idiopathic diarrhoea shortened the time to resolution of signs to 3.9 days from 6.6 days (Kelley et al, 2009).
The mean faecal score for cats on a probiotic decreased from 6.0 to 4.4, representing a significantly firmer stool character. A total of 72% of owners said their cat’s diarrhoea improved after a 21-day course of synbiotic supplementation (Hart et al, 2012).
Studies of L acidophilus in cats have shown a decrease in Clostridium species (Marshall-Jones et al, 2006). Administration of Lactobacillus group II and E faecium to 27 juvenile cheetahs significantly increased bodyweight and improved faecal quality (Koeppall et al, 2006).
Six weeks of E faecium SF68 in 20 dogs with chronic naturally acquired subclinical giardiasis failed to affect giardial cyst shedding or faecal giardial antigen and did not alter innate or adaptive immune responses (Simpson et al, 2009).
In dogs with food-responsive diarrhoea, a probiotic cocktail had beneficial effects on intestinal cytokines and microbiota, although the signs improved with the diet. Duodenal Il-10 messenger RNA (mRNA) levels decreased and colonic interferon-gamma mRNA levels increased. While cytokine patterns changed in vitro in response to treatment, the changes were not significantly associated with the clinical response (Sauter et al, 2005).
The microbiome is the genetic mass of microorganisms and their environment in various body areas. The GI microbiome is thought to be disturbed in IBD, a situation termed dysbiosis (Figure 1). The bacterial changes are thought to be associated with altered microbiota metabolic functions that may exacerbate the inflammatory state – for example, decreased short-chain fatty acids, altered amino acid metabolism, changes in redox equilibrium and altered bile acid metabolism (Schmitz and Suchodolski, 2016).
A synbiotic (probiotic plus prebiotic) study on the GI microbiome of healthy dogs and cats showed little change in the predominant bacterial phyla in faeces, although there was a higher abundance of probiotic bacteria in the faeces (Garcia-Mazcorro et al, 2011). The intestinal microbiome generally reverts back to the population present before probiotic supplementation shortly after the probiotic is stopped.
The combination probiotic VSL#3 restores tight junctions (claudin-2, occludin and adherens junction proteins) in the intestine in dogs with IBD (Rossi et al, 2014). Another study on the effects of VSL#3, compared to treatment with prednisolone and metronidazole, in 20 dogs with IBD showed a significant decrease in clinical and histological scores with both treatments; however, probiotic treatment increased regulatory T-cell markers (TGF-β+ and FoxP3+; Rossi et al, 2014). The dogs treated with probiotics also had a normalisation of the microbiome dysbiosis.
The effect of supplementing E faecium SF68 on immune function responses, after administering a multivalent vaccine, was evaluated in kittens. E faecium SF68 was recovered from the faeces of seven of the nine cats. The percentage of CD4+ lymphocytes was significantly higher in the treatment group, but no differences in measurements of any other immune parameters between groups (Veir et al, 2007). L acidophilus DSM 13241 administration resulted in higher eosinophil counts, along with changes in monocyte and granulocyte populations in cats (Marshall-Jones et al, 2006).
In puppies given a diet supplemented with E faecium (SF68) from weaning to one year old, faecal IgA and canine distemper virus vaccine-specific circulating IgG and IgA were higher in the probiotic group compared to a control group (Benyacoub et al, 2003).
Supplementation of L acidophilus DSM 13241 to 15 healthy adult cats associated the recovery of the probiotic from faeces with a significant reduction in Clostridium species and E faecalis (Baillon and Butterwick, 2003). However, the immunomodulatory effects reported were based on decreased lymphocyte and increased eosinophil populations and increased activities of peripheral blood phagocytes.
The relevance of these findings is unclear, because this study was not a randomised trial and the changes reported in the populations of peripheral blood cells cannot be extrapolated into evidence of systemic health benefits. Overall, the clinical relevance of these changes is hard to determine.
While the changes indicate something is changing in the immune system, they do not necessarily indicate whether they are beneficial and how they may be related to the potential for clinical efficacy. Nonetheless, they indicate the potential for probiotics to have some effect on the immune system.
In rats and pigs, probiotic treatments have shown to lower uraemia. In a case study of big cats with azotaemia, serum urea nitrogen and creatinine concentrations decreased after 60 days of probiotic treatment, although the concurrent treatments varied and the effect on quality of life of survival time is unclear (McCain et al, 2011). Another study of cats with naturally occurring azotaemia found supplementation with a synbiotic had no effect on the level of azotaemia (Rishniw and Wynn, 2011).
The lactic acid bacteria in canine and feline GI microflora have been shown to degrade oxalates (Murphy et al, 2009). This could help reduce intestinal oxalate absorption, thereby decreasing the amount excreted in the urine.
There has also been some interest in using probiotics in humans to prevent or treat urinary or vaginal infections (Reid et al, 1990).
Gut microbes can produce hormones and neurotransmitters identical to those produced by humans and gut bacteria directly stimulate afferent neurons of the enteric nervous system to send signals to the brain via the vagus nerve.
In humans, the GI microbiome is thought to impact human brain health in many ways. If dysbiosis is present, the microbiome may produce systemic and/or CNS inflammation, bacterial proteins may cross-react with human antigens and bacterial enzymes may produce neurotoxic metabolites, such as D-lactic acid and ammonia. Even otherwise beneficial metabolites, such as short-chain fatty acids, may exert neurotoxicity.
Through these varied mechanisms, gut microbes can affect sleep, stress reactivity, memory, mood, cognition and possibly appetite. In humans, impairment of the brain-gut axis signalling is associated with gut inflammation, chronic abdominal pain syndrome, irritable bowel syndrome and eating disorders (Galland, 2014).
Probiotics have shown positive effects on rodents’ learning ability, memory and anxiety (Desbonnet et al, 2008).
Human patients with systemic inflammatory diseases – such as rheumatoid arthritis, IBD and chronic liver disease – commonly develop debilitating symptoms from changes in brain function. In a mouse model of liver inflammation, the probiotic VSL#3 treatment attenuated behaviours, such as social withdrawal and immobility, without affecting disease severity, gut microbiota composition or gut permeability. These events were paralleled by changes in markers of systemic immune activation, including decreased circulating TNF-α levels (D’Mello et al, 2015).
The causes of obesity are complex and include genetic, endocrine, neural, sociocultural and behavioural factors. Alterations in the gut microbiota of obese versus lean rodents and people have also been established.
Several studies in humans have addressed the relationship between the two main intestinal bacterial phyla (Firmicutes and Bacteroidetes) and their subgroups, which make up 90% of the bacteria. Some of these studies have reported decreased proportions of Bacteroidetes and sometimes an increased proportion of Firmicutes in obese humans. An increase in faecal proportions of Bacteroidetes and decrease in Firmicutes during weight loss has also been reported (Arora et al, 2013).
The gut microbiota can contribute to obesity by improving the ability to ferment indigestible dietary polysaccharides into short-chain fatty acids, which can provide up to 10% of the daily energy supply. The microbiota can also modify the expression of genes involved in macronutrient metabolic pathways.
Studies have also suggested diet-induced alterations in microbial composition contribute to regulating aspects of energy balance, so there is a dependency of the microbes on the diet, as well as an effect of the microbes on the use of food (Million et al, 2013).
Transplanting germ-free mice with the microbiota from obese mice increased body fat and GI Firmicutes compared to transplantation from lean mice (Arora et al, 2013). On the other hand, administration of Lactobacillus rhamnosus PL60 to obese mice resulted in weight loss and decreased fat with no effect on energy intake.
Rats fed Lactobacillus gasseri SBT2055 have also been reported to show a decrease in visceral fat and a decrease in postprandial blood glucose. Theories about the anti-obesity effects of some probiotics include an increase in conjugated linoleic acid, an increase in brown tissue thermogenesis, decreased absorption of lipids, altered activity in the brain’s appetite centre and an increase in the fasting-induced adipose factor (Million et al, 2013).
Microbial control of eating behaviour may include affecting the microbial influence on reward and satiety pathways, production of toxins that alter mood, changes to receptors – including taste receptors – and disturbance of the vagus nerve.
No studies have yet reported on using probiotics for behaviour or for weight management in cats or dogs and studies in humans and rodents are inconsistent. The variability in both the studies, and in the effects of different probiotics, underline the difference between the products and differing possible individual responses.
Many clinicians have tried probiotics with minimal success and are tempted to say they are not beneficial. This is similar to using an unspecified antibiotic without success and deeming all antibiotics ineffective.
Like antibiotics, the type (strains) and amount of bacteria need to be right for the specific animal and its disease. Some studies have shown no effect with probiotics and the author has tried to present some that do show benefits.
When selecting a probiotic, study the research for proven effectiveness for the disorder being treated and the dosage.
