Difference between revisions of "Management of Acute Diarrhoea"

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Pyrexia and haemorrhagic diarrhoea appear to be clinical findings associated with antibiotic prescription,<ref name=":6"/>,<ref name=":7"/> indicating there may be a concern regarding the development of septicaemia caused by bacterial translocation across a damaged intestinal epithelium.  However, 88%6 and 37.5%7 of normothermic animals were prescribed antibiotics, making concern over sepsis a less likely justification. Furthermore, multiple studies demonstrate that bacteraemia is not necessarily associated with clinical disease, questioning the use of antibiotics even if bacteraemia may be present.<ref name=":8">Unterer S, Lechner E, Mueller RS et al. Prospective study of bacteraemia in acute haemorrhagic diarrhoea syndrome in dogs. Vet Rec 2015; 176(12): 309. </ref><ref name=":9">Unterer S, Strohmeyer K, Kruse BD, Sauter-Louis C, Hartmann K. Treatment of aseptic dogs with hemorrhagic gastroenteritis with amoxicillin/clavulanic acid: a prospective blinded study. J Vet Intern Med 2011; 25(5): 973-979.</ref><ref name=":10">Mortier F, Strohmeyer K, Hartmann K, Unterer S. Acute haemorrhagic diarrhoea syndrome in dogs: 108 cases. Vet Rec 2015; 176(24): 627.</ref><ref name=":11">Dahlinger J, Marks SL, HirshDC. Prevalence and identity of translocating bacteria in healthy dogs. J Vet Intern Med 1997; 11(6): 319-322.</ref> However, the potential for development of septicaemia or sepsis is a valid concern and if suspected due to deteriorating systemic clinical signs, haematological changes and/or positive blood culture, then appropriate parenteral antibiotics should be started immediately.
 
Pyrexia and haemorrhagic diarrhoea appear to be clinical findings associated with antibiotic prescription,<ref name=":6"/>,<ref name=":7"/> indicating there may be a concern regarding the development of septicaemia caused by bacterial translocation across a damaged intestinal epithelium.  However, 88%6 and 37.5%7 of normothermic animals were prescribed antibiotics, making concern over sepsis a less likely justification. Furthermore, multiple studies demonstrate that bacteraemia is not necessarily associated with clinical disease, questioning the use of antibiotics even if bacteraemia may be present.<ref name=":8">Unterer S, Lechner E, Mueller RS et al. Prospective study of bacteraemia in acute haemorrhagic diarrhoea syndrome in dogs. Vet Rec 2015; 176(12): 309. </ref><ref name=":9">Unterer S, Strohmeyer K, Kruse BD, Sauter-Louis C, Hartmann K. Treatment of aseptic dogs with hemorrhagic gastroenteritis with amoxicillin/clavulanic acid: a prospective blinded study. J Vet Intern Med 2011; 25(5): 973-979.</ref><ref name=":10">Mortier F, Strohmeyer K, Hartmann K, Unterer S. Acute haemorrhagic diarrhoea syndrome in dogs: 108 cases. Vet Rec 2015; 176(24): 627.</ref><ref name=":11">Dahlinger J, Marks SL, HirshDC. Prevalence and identity of translocating bacteria in healthy dogs. J Vet Intern Med 1997; 11(6): 319-322.</ref> However, the potential for development of septicaemia or sepsis is a valid concern and if suspected due to deteriorating systemic clinical signs, haematological changes and/or positive blood culture, then appropriate parenteral antibiotics should be started immediately.
  
−
In certain cases, antibiotics may be prescribed due to concern over zoonotic disease, particularly if children or immunocompromised people are in close contact with the animal. However, use of antibiotics in healthy individuals can promote the establishment of a carrier state and may favour development of antimicrobial resistance.23  
+
In certain cases, antibiotics may be prescribed due to concern over zoonotic disease, particularly if children or immunocompromised people are in close contact with the animal. However, use of antibiotics in healthy individuals can promote the establishment of a carrier state and may favour development of antimicrobial resistance.<ref name=":23">Weese JS. Bacterial Enteritis in Dogs and Cats: Diagnosis, Therapy, and Zoonotic Potential. Vet Clin North Am Small Anim Pract 2011; 41(2): 287-309</ref>
  
 
Alternatively, it has been shown that medications may be prescribed due to owner expectation or pressure when antibiotics may be selected based on owner compliance and willingness to pay, rather than suitability for the bacterial infection in question.<ref name=":12">Mateus AL, Brodbelt DC, Barber N, Stark KD. Qualitative study of factors associated with antimicrobial usage in seven small animal veterinary practices in the UK. Prev Vet Med 2014; 117(1): 68–78. </ref>
 
Alternatively, it has been shown that medications may be prescribed due to owner expectation or pressure when antibiotics may be selected based on owner compliance and willingness to pay, rather than suitability for the bacterial infection in question.<ref name=":12">Mateus AL, Brodbelt DC, Barber N, Stark KD. Qualitative study of factors associated with antimicrobial usage in seven small animal veterinary practices in the UK. Prev Vet Med 2014; 117(1): 68–78. </ref>
  
−
Following detection of pathogenic bacteria in the faeces, irrespective of the pathogen isolated, the empirical use of antibiotics is not recommended in cases of uncomplicated acute diarrhoea. Antibiotic use should be considered only following detection of the bacteria, or its toxin, in patients with acute, severe disease (e.g. haemorrhagic gastroenteritis), or where there is concern regarding the development of sepsis. In these cases, antimicrobial selection should ideally follow in vitro sensitivity testing.23,24
+
Following detection of pathogenic bacteria in the faeces, irrespective of the pathogen isolated, the empirical use of antibiotics is not recommended in cases of uncomplicated acute diarrhoea. Antibiotic use should be considered only following detection of the bacteria, or its toxin, in patients with acute, severe disease (e.g. haemorrhagic gastroenteritis), or where there is concern regarding the development of sepsis. In these cases, antimicrobial selection should ideally follow in vitro sensitivity testing.<ref name=":23"/>,<ref name=":24">Hall E. Canine diarrhoea: a rational approach to diagnostic and therapeutic dilemmas. In Practice 2009; 31: 8-16.</ref>
  
 
Finally, antibiotics may be given in the hope that they will accelerate the resolution of the diarrhoea. A recent study of 31 dogs reported that dogs given metronidazole had a shorter time to resolution of diarrhoea compared to control dogs receiving a placebo.<ref name=":13">Langlois DK, Koenigshof AM, Mani R. Metronidazole treatment of acute diarrhea in dogs: A randomized double blinded placebo-controlled clinical trial. J Vet Intern Med 2019 REF</ref> However, another study of 60 dogs reported that whilst dogs given metronidazole recovered slightly faster than those given a placebo, the group given probiotics recovered fastest.<ref name=":14">Shmalberg J, Montalbano C, Morelli G, Buckley GJ. A Randomized Double Blinded Placebo-Controlled Clinical Trial of a Probiotic or Metronidazole for Acute Canine Diarrhea. Front Vet Sci 2019; 6: 163.</ref> Several further studies have reported the use of various probiotic formulations to accelerate the resolution of acute diarrhoea compared to a placebo.<ref name=":15">Kelley RL, Minikhiem D, Kiely B, et al. Clinical benefits of probiotic canine-derived Bifidobacterium animalis strain AHC7 in dogs with acute idiopathic diarrhea. Vet Ther 2009; 10(3): 121-130.</ref><ref name=":16">Kelley RL, Minikhiem D, Kiely B, et al. Clinical benefits of probiotic canine-derived Bifidobacterium animalis strain AHC7 in dogs with acute idiopathic diarrhea. Vet Ther 2009; 10(3): 121-130.</ref>-<ref name=":17">Nixon SL, Rose L, Muller AT. Efficacy of an orally administered anti-diarrheal probiotic paste (Pro-Kolin Advanced) in dogs with acute diarrhea: A randomized, placebo-controlled, double-blinded clinical study. J Vet Intern Med 2019; 33(3): 1286-1294.</ref><ref name=":18">Ziese AL, Suchodolski JS, Hartmann K, et al. Effect of probiotic treatment on the clinical course, intestinal microbiome, and toxigenic Clostridium perfringens in dogs with acute hemorrhagic diarrhea. PLoS One 2018; 13: e0204691.</ref> Given the widespread concern over growing antimicrobial resistance, nutraceuticals may be a more appropriate choice for first-line management of acute diarrhoea compared to antibiotics.<ref name=":13"/>  
 
Finally, antibiotics may be given in the hope that they will accelerate the resolution of the diarrhoea. A recent study of 31 dogs reported that dogs given metronidazole had a shorter time to resolution of diarrhoea compared to control dogs receiving a placebo.<ref name=":13">Langlois DK, Koenigshof AM, Mani R. Metronidazole treatment of acute diarrhea in dogs: A randomized double blinded placebo-controlled clinical trial. J Vet Intern Med 2019 REF</ref> However, another study of 60 dogs reported that whilst dogs given metronidazole recovered slightly faster than those given a placebo, the group given probiotics recovered fastest.<ref name=":14">Shmalberg J, Montalbano C, Morelli G, Buckley GJ. A Randomized Double Blinded Placebo-Controlled Clinical Trial of a Probiotic or Metronidazole for Acute Canine Diarrhea. Front Vet Sci 2019; 6: 163.</ref> Several further studies have reported the use of various probiotic formulations to accelerate the resolution of acute diarrhoea compared to a placebo.<ref name=":15">Kelley RL, Minikhiem D, Kiely B, et al. Clinical benefits of probiotic canine-derived Bifidobacterium animalis strain AHC7 in dogs with acute idiopathic diarrhea. Vet Ther 2009; 10(3): 121-130.</ref><ref name=":16">Kelley RL, Minikhiem D, Kiely B, et al. Clinical benefits of probiotic canine-derived Bifidobacterium animalis strain AHC7 in dogs with acute idiopathic diarrhea. Vet Ther 2009; 10(3): 121-130.</ref>-<ref name=":17">Nixon SL, Rose L, Muller AT. Efficacy of an orally administered anti-diarrheal probiotic paste (Pro-Kolin Advanced) in dogs with acute diarrhea: A randomized, placebo-controlled, double-blinded clinical study. J Vet Intern Med 2019; 33(3): 1286-1294.</ref><ref name=":18">Ziese AL, Suchodolski JS, Hartmann K, et al. Effect of probiotic treatment on the clinical course, intestinal microbiome, and toxigenic Clostridium perfringens in dogs with acute hemorrhagic diarrhea. PLoS One 2018; 13: e0204691.</ref> Given the widespread concern over growing antimicrobial resistance, nutraceuticals may be a more appropriate choice for first-line management of acute diarrhoea compared to antibiotics.<ref name=":13"/>  
  
 
==Rationale and evidence for the use of probiotics in acute diarrhoea==
 
==Rationale and evidence for the use of probiotics in acute diarrhoea==
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The rationale for the use lactic acid probiotic bacteria (LAB) in the management of acute diarrhoea is based on their ability to suppress growth of enteric pathogens. LAB lower intestinal pH, provide increased competition for nutrients and mucosal binding sites, and can exert a direct inhibitory effect through production of antimicrobial substances. Furthermore, probiotics can activate innate and adaptive immune responses to increase host disease resistance.19
+
The rationale for the use lactic acid probiotic bacteria (LAB) in the management of acute diarrhoea is based on their ability to suppress growth of enteric pathogens. LAB lower intestinal pH, provide increased competition for nutrients and mucosal binding sites, and can exert a direct inhibitory effect through production of antimicrobial substances. Furthermore, probiotics can activate innate and adaptive immune responses to increase host disease resistance.<ref name=":19"/>
  
 
Probiotics are commonly combined with other ingredients that possess properties which can be useful in animals experiencing diarrhoea. Various clays have absorptive and adsorptive properties, meaning they can bind fluid and bacterial or viral toxins.<ref name=":20">Fomina M, Skorochod I. Microbial Interaction with Clay Minerals and Its Environmental and Biotechnological Implications. Minerals. 2020; 10(10):861.</ref> Soluble fibres, such as psyllium, can also be useful due to their gel-forming ability when mixed with water. Other common ingredients are the yeast wall extracts mannan-oligosaccharides (MOS) and beta-glucans which can play a role in preventing pathogenic bacteria binding to the intestinal wall and increasing disease resistance through the activation of intestinal immunity.<ref name=":21">Pignataro G, Di Prinzio R, Crisi PE, Belà B, Fusaro I, Trevisan C, De Acetis L, Gramenzi A. Comparison of the therapeutic effect of treatment with antibiotics or nutraceuticals on clinical activity and the fecal microbiome of dogs with acute diarrhea. Animals. 2021 Jun;11(6):1484.</ref>
 
Probiotics are commonly combined with other ingredients that possess properties which can be useful in animals experiencing diarrhoea. Various clays have absorptive and adsorptive properties, meaning they can bind fluid and bacterial or viral toxins.<ref name=":20">Fomina M, Skorochod I. Microbial Interaction with Clay Minerals and Its Environmental and Biotechnological Implications. Minerals. 2020; 10(10):861.</ref> Soluble fibres, such as psyllium, can also be useful due to their gel-forming ability when mixed with water. Other common ingredients are the yeast wall extracts mannan-oligosaccharides (MOS) and beta-glucans which can play a role in preventing pathogenic bacteria binding to the intestinal wall and increasing disease resistance through the activation of intestinal immunity.<ref name=":21">Pignataro G, Di Prinzio R, Crisi PE, Belà B, Fusaro I, Trevisan C, De Acetis L, Gramenzi A. Comparison of the therapeutic effect of treatment with antibiotics or nutraceuticals on clinical activity and the fecal microbiome of dogs with acute diarrhea. Animals. 2021 Jun;11(6):1484.</ref>

Revision as of 14:30, 26 May 2022

Management of Acute Diarrhoea

Acute diarrhoea is a common complaint seen in first-opinion small animal veterinary practice. One study reported 14.9% of dogs had experienced an episode of diarrhoea within the previous two-week period[1]

another reported 28.6% of dogs visiting the vets had diarrhoea as their presenting complaint or had experienced an episode of diarrhoea within the previous month.[2] Data from pet cats is limited, but one study showed that prevalence of diarrhoea in a rescue cat population was 11.9%.[3]

Diarrhoea is defined as an increase in frequency, fluidity or volume of faeces and is a common complaint in dogs and cats.[4] Diarrhoea lasting for less than two weeks is generally described as acute[5] and commonly resolves without the requirement for veterinary intervention.[1] Therefore, animals are often presented at the vets due to owner concern or difficulty in managing the symptoms. Despite the fact that it is often self-limiting and likely to resolve with symptomatic treatment alone, antibiotics are frequently prescribed as part of the therapeutic management plan.

Ideally, antibiotics should be reserved for cases where pathogenic bacteria have been detected in the faeces of animals with severe disease, or if there is a high risk of septicaemia. In reality, it was found that 71% of canine cases presenting with diarrhoea in first-opinion practice were given antibiotics.[6] This statistic has reduced according to a more recent study, in which 49.7% of dogs were prescribed antibiotics when initially presented at the vets with diarrhoea.[7] Despite the fact that almost half of the dogs in the latter study were dispensed antibiotics, faecal bacteriology/ parasitology was performed in only 3.2% of these cases, suggesting a large discrepancy between antibiotic administration and prior demonstration of an underlying bacterial infection.

Why are antibiotics so commonly prescribed?

Pyrexia and haemorrhagic diarrhoea appear to be clinical findings associated with antibiotic prescription,[6],[7] indicating there may be a concern regarding the development of septicaemia caused by bacterial translocation across a damaged intestinal epithelium. However, 88%6 and 37.5%7 of normothermic animals were prescribed antibiotics, making concern over sepsis a less likely justification. Furthermore, multiple studies demonstrate that bacteraemia is not necessarily associated with clinical disease, questioning the use of antibiotics even if bacteraemia may be present.[8][9][10][11] However, the potential for development of septicaemia or sepsis is a valid concern and if suspected due to deteriorating systemic clinical signs, haematological changes and/or positive blood culture, then appropriate parenteral antibiotics should be started immediately.

In certain cases, antibiotics may be prescribed due to concern over zoonotic disease, particularly if children or immunocompromised people are in close contact with the animal. However, use of antibiotics in healthy individuals can promote the establishment of a carrier state and may favour development of antimicrobial resistance.[12]

Alternatively, it has been shown that medications may be prescribed due to owner expectation or pressure when antibiotics may be selected based on owner compliance and willingness to pay, rather than suitability for the bacterial infection in question.[13]

Following detection of pathogenic bacteria in the faeces, irrespective of the pathogen isolated, the empirical use of antibiotics is not recommended in cases of uncomplicated acute diarrhoea. Antibiotic use should be considered only following detection of the bacteria, or its toxin, in patients with acute, severe disease (e.g. haemorrhagic gastroenteritis), or where there is concern regarding the development of sepsis. In these cases, antimicrobial selection should ideally follow in vitro sensitivity testing.[12],[14]

Finally, antibiotics may be given in the hope that they will accelerate the resolution of the diarrhoea. A recent study of 31 dogs reported that dogs given metronidazole had a shorter time to resolution of diarrhoea compared to control dogs receiving a placebo.[15] However, another study of 60 dogs reported that whilst dogs given metronidazole recovered slightly faster than those given a placebo, the group given probiotics recovered fastest.[16] Several further studies have reported the use of various probiotic formulations to accelerate the resolution of acute diarrhoea compared to a placebo.[17][18]-[19][20] Given the widespread concern over growing antimicrobial resistance, nutraceuticals may be a more appropriate choice for first-line management of acute diarrhoea compared to antibiotics.[15]

Rationale and evidence for the use of probiotics in acute diarrhoea

The rationale for the use lactic acid probiotic bacteria (LAB) in the management of acute diarrhoea is based on their ability to suppress growth of enteric pathogens. LAB lower intestinal pH, provide increased competition for nutrients and mucosal binding sites, and can exert a direct inhibitory effect through production of antimicrobial substances. Furthermore, probiotics can activate innate and adaptive immune responses to increase host disease resistance.[21]

Probiotics are commonly combined with other ingredients that possess properties which can be useful in animals experiencing diarrhoea. Various clays have absorptive and adsorptive properties, meaning they can bind fluid and bacterial or viral toxins.[22] Soluble fibres, such as psyllium, can also be useful due to their gel-forming ability when mixed with water. Other common ingredients are the yeast wall extracts mannan-oligosaccharides (MOS) and beta-glucans which can play a role in preventing pathogenic bacteria binding to the intestinal wall and increasing disease resistance through the activation of intestinal immunity.[23]

Assessing the clinical outcomes of probiotic supplementation in dogs with acute diarrhoea has been the subject of numerous placebo-controlled studies.[17]-[21],[24] Amongst these studies, findings in the probiotic treated groups included: shorter times to diarrhoea resolution, [17] -[19] greater improvement in stool consistency score,18 faster improvement in Canine Haemorrhagic Diarrhoea Severity Index (CHDSI),18 greater decrease of faecal C. perfringens,[19] and a lower requirement for additional medical interventions. [17],[19]

Summary

Acute diarrhoea is often self-limiting and likely to resolve without veterinary intervention. Diagnostic investigations are infrequently performed in these cases and even when faecal analysis is carried out, the results can be difficult to interpret given that many potentially pathogenic bacteria are also found in healthy individuals. Antibiotics are still frequently prescribed to dogs or cats that present with acute diarrhoea, however this can contribute to the development of antibacterial resistance, as well as causing disruptions to the normal gastrointestinal microbiota and can result in adverse effects for the patient. Therefore, antibiotics should be reserved for specific cases where bacterial infection is confirmed or highly suspected, and/or there is concern of bacterial translocation or sepsis.

References

  1. ↑ 1.0 1.1 Hubbard K, Skelly BJ, McKelvie J, Wood JLN. Risk of vomiting and diarrhoea in dogs. Vet Rec 2007; 161: 755–757.
  2. ↑ Stavisky J, Pinchbeck GL, German AJ et al. Prevalence of canine enteric coronavirus in a cross-sectional survey of dogs presenting at veterinary practices. Vet Microbiol 2010; 140: 18–24
  3. ↑ German AC, Cunliffe NA, Morgan KL. Faecal consistency and risk factors for diarrhoea and constipation in cats in UK rehoming shelters. J Feline Med Surg 2017; 19(1): 57-65.
  4. ↑ Battersby I, Harvey A. Differential diagnosis and treatment of acute diarrhoea in the dog and cat. In Practice 2006; 28: 480-488.
  5. ↑ Chandler ML. The chronically diarrhoeic dog. In Pract 2002; 24: 18–27.
  6. ↑ 6.0 6.1 German AJ, Halladay LJ, Noble PJ. First-choice therapy for dogs presenting with diarrhoea in clinical practice. Vet Rec 2010; 167(21):810–814.
  7. ↑ 7.0 7.1 Singleton DA, Noble PJM, Sánchez-Vizcaíno F et al. Pharmaceutical Prescription in Canine Acute Diarrhoea: A Longitudinal Electronic Health Record Analysis of First Opinion Veterinary Practices. Front Vet Sci 2019; 6: 218.
  8. ↑ Unterer S, Lechner E, Mueller RS et al. Prospective study of bacteraemia in acute haemorrhagic diarrhoea syndrome in dogs. Vet Rec 2015; 176(12): 309.
  9. ↑ Unterer S, Strohmeyer K, Kruse BD, Sauter-Louis C, Hartmann K. Treatment of aseptic dogs with hemorrhagic gastroenteritis with amoxicillin/clavulanic acid: a prospective blinded study. J Vet Intern Med 2011; 25(5): 973-979.
  10. ↑ Mortier F, Strohmeyer K, Hartmann K, Unterer S. Acute haemorrhagic diarrhoea syndrome in dogs: 108 cases. Vet Rec 2015; 176(24): 627.
  11. ↑ Dahlinger J, Marks SL, HirshDC. Prevalence and identity of translocating bacteria in healthy dogs. J Vet Intern Med 1997; 11(6): 319-322.
  12. ↑ 12.0 12.1 Weese JS. Bacterial Enteritis in Dogs and Cats: Diagnosis, Therapy, and Zoonotic Potential. Vet Clin North Am Small Anim Pract 2011; 41(2): 287-309
  13. ↑ Mateus AL, Brodbelt DC, Barber N, Stark KD. Qualitative study of factors associated with antimicrobial usage in seven small animal veterinary practices in the UK. Prev Vet Med 2014; 117(1): 68–78.
  14. ↑ Hall E. Canine diarrhoea: a rational approach to diagnostic and therapeutic dilemmas. In Practice 2009; 31: 8-16.
  15. ↑ 15.0 15.1 Langlois DK, Koenigshof AM, Mani R. Metronidazole treatment of acute diarrhea in dogs: A randomized double blinded placebo-controlled clinical trial. J Vet Intern Med 2019 REF
  16. ↑ Shmalberg J, Montalbano C, Morelli G, Buckley GJ. A Randomized Double Blinded Placebo-Controlled Clinical Trial of a Probiotic or Metronidazole for Acute Canine Diarrhea. Front Vet Sci 2019; 6: 163.
  17. ↑ 17.0 17.1 17.2 17.3 Kelley RL, Minikhiem D, Kiely B, et al. Clinical benefits of probiotic canine-derived Bifidobacterium animalis strain AHC7 in dogs with acute idiopathic diarrhea. Vet Ther 2009; 10(3): 121-130.
  18. ↑ Kelley RL, Minikhiem D, Kiely B, et al. Clinical benefits of probiotic canine-derived Bifidobacterium animalis strain AHC7 in dogs with acute idiopathic diarrhea. Vet Ther 2009; 10(3): 121-130.
  19. ↑ 19.0 19.1 19.2 19.3 Nixon SL, Rose L, Muller AT. Efficacy of an orally administered anti-diarrheal probiotic paste (Pro-Kolin Advanced) in dogs with acute diarrhea: A randomized, placebo-controlled, double-blinded clinical study. J Vet Intern Med 2019; 33(3): 1286-1294.
  20. ↑ Ziese AL, Suchodolski JS, Hartmann K, et al. Effect of probiotic treatment on the clinical course, intestinal microbiome, and toxigenic Clostridium perfringens in dogs with acute hemorrhagic diarrhea. PLoS One 2018; 13: e0204691.
  21. ↑ 21.0 21.1 Li Y, Xia S, Jiang X, Feng C, Gong S, Ma J, Fang Z, Yin J and Yin Y (2021) Gut Microbiota and Diarrhea: An Updated Review. Front. Cell. Infect. Microbiol. 11:625210. doi: 10.3389/fcimb.2021.625210
  22. ↑ Fomina M, Skorochod I. Microbial Interaction with Clay Minerals and Its Environmental and Biotechnological Implications. Minerals. 2020; 10(10):861.
  23. ↑ Pignataro G, Di Prinzio R, Crisi PE, Belà B, Fusaro I, Trevisan C, De Acetis L, Gramenzi A. Comparison of the therapeutic effect of treatment with antibiotics or nutraceuticals on clinical activity and the fecal microbiome of dogs with acute diarrhea. Animals. 2021 Jun;11(6):1484.
  24. ↑ Gómez-Gallego C, Junnila J, Männikkö S, et al. A canine-specific probiotic product in treating acute or intermittent diarrhea in dogs: A double-blind placebo-controlled efficacy study. Vet Microbiol. 2016;197:122-128.
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