Table 2.

Summary of studies assessing the effect of different strategies to modulate gut microbiota.

Strategy	Reference	Design	Conclusion
Prebiotics	[82]	Twenty-seven IBD dogs were randomized to be fed with chondroitin sulphate and prebiotics (resistant starch, β-glucans and mannaoligosaccharides) or placebo in addition to a hydrolyzed diet and were evaluated after 30, 60, 90 and 180 days of treatment.	No significant differences were found between groups at any point for CIBDAI, WSAVA histologic score or fecal microbiota evaluated by PCR-RLFP.
	[83]	Thirteen dogs with FREs were randomized to be fed a combination of prebiotics (β-glucans and mannan oligosaccharides), chondroitin sulphate and glycosaminoglycans or placebo in addition to a hydrolyzed diet for 10 weeks. Relapse rate was monitored every 2 weeks until week 18.	No significant differences were found over time or between groups for CCECAI, endoscopy scoring or histological scoring, nor in the relapse rate after switching back to the original diet.
Probiotics	[88]	A systematic review of clinical effect of probiotics in prevention or treatment of gastrointestinal disease in dogs, including twelve studies concerning acute gastrointestinal disease and five concerning chronic gastrointestinal disease.	The current data point toward a very limited and possibly clinically unimportant effect for prevention or treatment of acute gastrointestinal disease. For chronic gastrointestinal disease, dietary intervention remains the major key in treatment, whereas probiotic supplement seems not to add significant improvement.
	[89]	Twenty dogs with IBD were randomized to receive multi-strain probiotic (VSL#3) or prednisolone/metronidazole, monitored for 60 days and re-evaluated 30 days after completing treatment.	The CIBDAI and duodenal histology scores decreased between days 0 and 90 in both groups.
	[90]	Twenty dogs with CIEs were randomized to receive Saccharomyces boulardii (109/kg BID) or a placebo, in addition to conventional treatment (hydrolyzed protein diet, prednisolone and antibiotic) for 60 days.	The administration of yeast was associated with a lower CCECAI score on days 45 and 60
Symbiotics	[84]	Twenty-four dogs with CIE were randomized to be fed a hydrolyzed diet and administered symbiotic-IgY (β-glucans, mannan oligosaccharides, D-mannose, Lactobacillus acidophilusn, Lactobacillus casei, Enterococcus faecium, Bacillus subtilis and immunoglobulin IgY derived from chicken egg yolk) or placebo for 6 weeks.	Dogs administered supplement exhibited decreased levels of fecal calprotectin and high-sensitivity C-reactive protein two weeks post-treatment, decreased levels of hs-CRP two- and six-weeks post-treatment, increased numbers of mucosal Clostridia and Bacteroides and decreased numbers of Enterobacteriaceae in colonic biopsies at the completion of the trial.
Fecal microbiota transplantation	[96]	Diversity analysis, differential abundance analysis and machine learning algorithms were applied to investigate the differences in microbiome composition between healthy and pre-FMT CIE-affected dogs, while CCECAI changes and microbial diversity metrics were used to evaluate oral freeze-dried fecal microbiota capsules’ effects.	In the healthy/pre-FMT comparison, differences were noted in alpha and beta diversity and a list of differentially abundant taxa was identified. Improvement of clinical signs was noted in 74% (20/27) of CIE-affected dogs, together with a decrease in CCECAI. Alpha and beta diversity variations between pre- and post-FMT were observed for each receiver, with a high heterogeneity in the response.
Fecal microbiota transplantation	[97]	A 10-year-old toy poodle diagnosed with IBD received nine FMTs by rectal enema within 6 months. 16S rRNA sequence analysis was performed before and after the FMTs.	Fecal microbiome diversity after FMT resembled that of the healthy donor dog’s fecal microbiome. The clinical symptoms improved remarkably with regard to the changes in the fecal microbiome. No observable side effects were noted.
	[98]	FMTs were performed in nine dogs with IBD. Fecal microbiome was examined via 16S rRNA sequencing in three dogs.	The proportion in Fusobacteirum in the post-FMT fecal microbiome was increased, and the CIBDAI decreased in all dogs.
	[99]	A 7-year-old Shiba dog diagnosed with protein-losing NRE received one FMT along with chlorambucil.	A single FMT via endoscopic procedure into the cecum and colon drastically recovered clinical signs and clinicopathological abnormalities and corrected dysbiosis in the dog. No recurrences or adverse events were observed.
	[100]	A 6-year-old Labrador dog diagnosed with IBD received FMT in the form of frozen oral capsules (five capsules/10 kg body weight for five consecutive days, along with prednisolone).	The CIBDAI switched from mild to clinically insignificant disease in 21 days. In the 18 months following FMT, the dog had some relapses defined as milder than before the FMT. No adverse effects were reported.
	[101]	Forty-one dogs with CIEs not responding to diet, probiotics or immunosuppression. Included dogs received one to five FMTs with fresh frozen feces via rectal enemas.	In 31/41 dogs (76%), FMT was associated with clinical improvement. In 20/41 dogs, the dose of corticosteroids was decreased and antibiotics were interrupted. The CIBDAI significantly decreased.
	[102]	Thirteen dogs with IBD were randomized to receive either FMT or placebo via rectal enema, along with cortisteroid therapy and a hypoallergenic diet, and were monitored for one month.	No significant differences in CCECAI between groups.
	[103]	Sixteen dogs with IBD received FMT, nine via an endoscopic procedure with five of them also given the transplant orally, and seven were administered by frozen capsules. They were monitored for 3 months. At the time of transplantation, all subjects were receiving immunosuppressants, antibiotics or both.	A clinical improvement was shown in most patients after transplantation, whether performed orally or endoscopically.
Bile acid sequestrants	[104]	One dog with NRE and one with IRE but with unacceptable corticosteroids side effects received cholestyramine (2 g q12–24 h).	Treatment with cholestyramine resulted in marked improvement of fecal consistency, frequency of defecation and activity level in both dogs.