Effect of faecal microbial transplantation on clinical outcome, faecal microbiota and metabolome in dogs with chronic enteropathy refractory to diet

Abstract

Chronic enteropathy (CE) is a common complaint in canine gastroenterology. Recently, faecal microbiota transplantation (FMT) gained attention as a treatment strategy. However, the efficacy and long-term impact of FMT is still unclear. Clinical index (CIBDAI), faecal microbiota and metabolome were monitored in 20 CE dogs refractory to diet before (T0) and 3 months (T3) after FMT. Further data were retrospectively collected up to 1-year after FMT. Significant improvements were observed in CIBDAI, Dysbiosis Index (DI), and primary (PBAs) and secondary (SBAs) faecal bile acids and propionate one month (T1) after FMT (CIBDAI (median and range): T0 5 (1-9) vs. T1 1 (0-5), p < 0.0001; DI (median and range): T0 -0.1 (-5.6 to 3.8) vs. T1 -2.1 (-5.7 to 4.7), p < 0.05; PBAs decreased by 57%, SBAa increased by 41%; propionate increased by 20%). According to CIBDAI, 17 dogs clinically improved up to T3, and 10 dogs remained clinically stable up to one year after FMT. Alpha- and beta-diversity of the faecal microbiota of CE dogs did not differ, neither before nor after FMT, from that of 17 healthy controls. The results highlight that CE dogs refractory to diet with mild clinical signs and dysbiosis may benefit long-term from treatment with FMT.

Fig. 1

Study design and patient data – clinical evaluations and faecal sampling – collected during the study.

Fig. 2

CIBDAI index assessed in 20 CE dogs (all values a, median and range b) before (T0) and 30 (T1), 60 (T2) and 90 (T3) days after FMT. Values up to 3 are indicative of clinically insignificant disease.

Fig. 3

Dysbiosis Index (a-b) and Peptoacetobacter hiranonis abundance (log DNA, c-d) assessed in 20 CE dogs before (T0) and 30 (T1), 60 (T2) and 90 (T3) days after FMT. The grey shaded area is the reference abundance for P. hiranonis, and values < 0 indicate normal DI, > 0 and < 2 indicate mild changes in bacterial populations. The red dots represent dogs in the (ab) group receiving antibiotic therapy 30 to 60 days before FMT (T0). *P < 0.05.

Fig. 4

(a) Alpha diversity (observed feature) and (b) Beta diversity (Bray–Curtis distance) in healthy dogs (HC) and dogs with CE assessed before (T0) and 30 (T1), 60 (T2) and 90 (T3) days after FMT; (c) Beta diversity according to Bray–Curtis distance categorized based on the interpretation of the Dysbiosis Index (DI) in 20 dogs with CE and 17 healthy dogs.

Fig. 5

Relative abundance (%) of Erysipelatoclostridium spp. in healthy dogs (HC) and dogs with CE assessed before (T0) and 30 (T1), 60 (T2) and 90 (T3) days after FMT.

Fig. 6

(a and c): Spearman correlation between the abundance of P. hiranonis (Log DNA) in 20 CE dogs before FMT (T0) and total (%) primary bile acids (PBA, 6A) and secondary bile acids (SBA, 6C). The grey shaded area is the reference abundance for P. hiranonis, (b) and (d): Faecal primary and secondary bile acids concentrations (6b and d, %) assessed before (T0) and 30 (T1), 60 (T2) and 90 (T3) days after FMT. The grey shaded area is the reference abundance. In both graphs, T0 vs. T1 was significantly different (P < 0.01).

Fig. 7

The faecal calprotectin levels (μg/g all values a, median and range b) assessed before (T0) and 30 (T1), 60 (T2) and 90 (T3) days after FMT. The grey shaded area represents the reference interval for the assay. The Minimum Quantification Level (MQL) is 23.7 μg/g, and values < MQL are set to 10 in the graph.